ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC
Conditions
Keywords
Phase 1, Phase 2, safety, pharmacokinetic, pharmacodynamic, efficacy
Brief summary
Phase 1 and 2 trial to study the safety, pharmacokinetics, pharmacodynamics, patient reported outcomes and efficacy of PF-06463922 in ALK + advanced non-small cell lung cancer patients and ROS1+ advanced non small cell lung cancer patients .
Interventions
DRUGPF-06463922
Oral, starting dose 10mg once a day, dose escalation in Phase 1 until recommended Phase 2 dose determined, continuous daily dosing, cycles lasting 21 days
DRUGCrizotinib
Oral, starting dose of 250 mg BID continuous daily dosing every 21 days
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA) approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment. * Disease Status Requirements: Phase 1: ALK-positive NSCLC and ROS1-positive patients must either be treatment naïve in the advanced setting or have had disease progression after at least 1 previous ALK/ROS1 inhibitor therapy(ies). Phase 2: ALK-positive NSCLC patients must either be or have had: * Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ALK inhibitor therapy allowed). * Disease progression after crizotinib only. No prior chemotherapy is allowed in the metastatic disease setting. * Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the metastatic disease setting. * Disease progression after 1 prior ALK inhibitor therapy other than crizotinib. Patients may have had any number of prior chemotherapy regimens in any disease setting. * Disease progression after 2 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting. * Disease progression after 3 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting. ROS1-positive NSCLC patients may be: * Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ROS inhibitor therapy). * Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies). * Tumor Requirements: All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks prior to study entry) will be eligible. Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) are eligible. * Adequate Bone Marrow, Pancreatic Function, Renal Function and Liver Function. * Negative Serum pregnancy test for females of childbearing potential
Exclusion criteria
* Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry. * Systemic anti cancer therapy completed within a minimum of 5 half lives of study entry. * Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody. * Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. * Clinically significant cardiovascular disease (that is, active or \<3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), second-degree or third-degree AV block (unless paced) or any AV block with PR \>220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as \<50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc \>470 msec, or congenital long QT syndrome. * History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis. * Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are sensitive CYP2B6 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | 3 years | Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 milliliter (mm) on Target Lesions electronic case report form (eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 percent (%) or more decrease in sum of lesion dimensions (SLD) of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review. |
| Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Cycle 1 (21 days) | DLT: any of following adverse events (AEs) attributable to PF-06463922: (1) hematologic: grade 4 neutropenia for \>7 days; febrile neutropenia; grade\>=3 neutropenic infection; grade\>=3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade\>=3 pancreatitis; grade\>=3 toxicities (excluding grade \>=3 laboratory abnormalities not requiring dose modifications) persisting after optimal treatment with standard medical therapy; symptomatic grade \>=3 QT interval corrected for heart rate (QTc) prolongation, or asymptomatic grade \>=3 prolongation that had been confirmed by repeat testing, re-evaluation by qualified person, persisted after correction of reversible causes; \>=20% decrease from baseline in left ventricular ejection fraction (LVEF); (3) other: failure to deliver at least 16 out of 21 prescribed daily total dose due to toxicities attributable to study drug; failure to restart dosing after 21 days (1 cycle) delay due to toxicity attributable to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall and Intracranial Objective Response (Phase 1) | From start of study treatment until CR or PR (maximum of 8 years approximately) | Objective response (OR) refers to confirmed CR or PR according to RECIST version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review. |
| Time to Tumor Response (TTR) and Intracranial TTR (Phase 1) | From start of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 8 years approximately) | Time to tumor response (TTR) was defined as the time from the first dose of study treatment to the first documentation of objective tumor response (CR or PR). For participants whose objective response proceeded from PR to CR, the onset of PR was taken as the onset of response. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. TTR was only calculated for the subgroup of participants with a confirmed objective tumor response. Intracranial TTR was only calculated for participants with confirmed intracranial objective response. Results presented here were based on independent central review. |
| Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately) | Duration of response(DOR): time from first documentation of objective tumor response (CR/PR) to first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. DOR: calculated for subgroup of participants with confirmed objective tumor response. Intracranial DOR: calculated for participants with confirmed intracranial objective response. CR:disappearance of all non-lymph node target lesions (where all target lesions are recorded with length of 0mm on Target Lesion eCRF). Any pathological lymph node (recorded as target lesion) must have reduction in short axis to \<10mm. PR:30% or more decrease in SLD of target lesion, taking as reference baseline SLD. PD:20% or more increase in the SLD of target lesions relative to baseline or smallest SLD (nadir) recorded since first dose. In addition, also demonstrate absolute increase of at least 5mm (\>=5mm) relative to baseline or smallest SLD (nadir) recorded since first dose. |
| Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | 12 and 24 weeks | Tumor response was evaluated according to RECIST version 1.1, and disease control: confirmed CR, confirmed PR, or stable disease (SD). Intracranial assessment was only performed for participants CNS metastases. CR was defined as disappearance of all non-lymph node target lesions (where all target lesions are recorded with length of 0mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as 30% or more decrease in SLD of target lesions, taking as reference baseline SLD. Progressive disease: 20% or more increase in SLD of target lesions relative to baseline or smallest SLD (nadir) recorded since first dose. In addition to relative increase of 20%, SLD must also demonstrate absolute increase of at least 5mm (\>=5mm) relative to baseline or smallest SLD (nadir) recorded since first dose. Results presented here were based on independent central review. |
| Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1) | 3 years | The probability of the first event being a CNS progression, a non-CNS progression, or death was evaluated with a competing risk approach by estimating cumulative incidence functions (range: 0-1) relative to the analysis set. The time to first event being a Competing Event (either CNS progression or non CNS progression or Death) was defined as time from first dose until the date of that specific event. Participants not known to have any of the Competing Events were censored on the date they were last assessed for disease status for PFS. Participants who presented one type of event were counted as a competing cause of failure for the analysis of other type of events. For each type of event, the cumulative incidence function corresponding to the nearest time point preceding 1 year is presented. The results are based on independent central review. |
| Progression-Free Survival (PFS) (Phase 1) | From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately) | PFS was defined as the time from the first dose of study treatment to the first documentation of objective PD or to death on study due to any cause, whichever came first. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. Results presented here were based on independent central review. |
| Overall Survival (OS) (Phase 1) | 3 years | OS was defined as the time from first dose to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method. |
| Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups. | Maximum observed plasma concentration (Cmax) of PF-06463922 was observed directly from data. |
| Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups). | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 was observed directly from data. |
| Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups. | Tmax of PF-06463922 was observed directly from data as time of first occurrence. |
| Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups). | Tmax of PF-06463922 was observed directly from data as time of first occurrence. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups) | Tau refers to the dosing interval, and it equals to 12 or 24 hours for BID or QD dosing, respectively. AUCtau was determined using linear/log trapezoidal method. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups. | AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase. |
| Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups. | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. |
| Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. |
| Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups. | Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf\*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase. |
| Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups) | Rac was calculated as Day 15 AUCtau/Day -7 AUCtau or Day 1 AUCtau, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (12 and 24 hours for BID and QD dosing regimen, respectively). |
| Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups. | Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. |
| Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups) | Rss was calculated as Day 15 AUCtau/Day -7 AUCinf, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (12 and 24 hours for BID and QD dosing regimen, respectively), and AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. |
| Renal Clearance (CLr) of PF-06463922 (Phase 1) | 0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15 | Renal clearance was calculated as Aetau/AUCtau, where Aetau was the cumulative amount of drug recovered unchanged in urine up to dosing interval tau (24 hours for QD dosing regimen), and AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen). |
| Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1) | 0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15 | Dosing interval was 24 hours for QD dosing regimen. Aetau% was calculated as 100\*Ae24/dose, where Ae24 was the cumulative amount of drug recovered unchanged in urine up to 24 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Cmax of midazolam was observed directly from data. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflected the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflected the PK assessment after multiple doses of PF-06463922 were administered. |
| Time for Cmax (Tmax) of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Tmax of midazolam was observed directly from data as time of first occurrence. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of midazolam was determined using linear/log trapezoidal method. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. |
| Apparent Oral Clearance (CL/F) of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. |
| Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf\*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. |
| Terminal Half-Life of Midazolam (Phase 1) | Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. |
| Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 1) | Screening (up to 28 days) | Plasma circulating nucleic acid (CNA) samples were analyzed for ALK kinase domain mutations by digital polymerase chain reaction (PCR) BEAMing technology. Number of participants with one or more ALK mutations is presented. |
| Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 1) | Screening (up to 28 days) | Tumor tissues from archived tissue specimens and/or a de novo biopsy were analyzed for ALK kinase domain mutations. Number of participants with one or more ALK mutations is presented. |
| Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | From start of study treatment until end of treatment (maximum of 8 years approximately) | European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ)-C30 (version 3.0) consists of 30 questions assessing 5 functional domains (physical, role, emotional, cognitive and social), global quality of life (QoL), disease/treatment related symptoms (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea), and the perceived financial impact of disease. Each scale was transformed to a range of 0 to 100 using standard EORTC algorithm. For global QoL and functional scales, higher score indicate better performance, and improvement was defined as an increase of at least 10 points, worsening was defined as a decrease of at least 10 points. For symptom scales, higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. |
| Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | From start of study treatment until end of treatment (maximum of 8 years approximately) | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. |
| Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Baseline, Day 1 of Cycle 1-52, and end of treatment (up to 3 years) | In Phase 1, the MMSE was collected to assess mental status. The MMSE is a 30 item questionnaire that tests 5 areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30 and minimum score is 0. Highest score indicates no cognitive impairment, lowest score indicates severe cognitive impairment. The MMSE was removed under Amendment 6 of the study protocol, and not required for Phase 2, as the tool was not considered meaningful for assessment of cognitive function. |
| Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | From first dose of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Time to tumor response (TTR) was defined as the time from the first dose of study treatment to the first documentation of objective tumor response (CR or PR). For participants whose objective response proceeded from PR to CR, the onset of PR was taken as the onset of response. TTR was only calculated for the subgroup of participants with a confirmed objective tumor response. Intracranial TTR was only calculated for participants with confirmed intracranial objective response. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review. |
| Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | From first dose of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Duration of response(DOR): time from first documentation of objective tumor response (CR/PR) to first documentation of PD or to death due to any cause, whichever occurred first. DOR: calculated for subgroup of participants with confirmed objective tumor response. Intracranial DOR: calculated for participants with confirmed intracranial objective response. CR:disappearance of all non-lymph node target lesions (where all target lesions are recorded with length of 0mm on Target Lesion eCRF). Any pathological lymph node (recorded as target lesion) must have reduction in short axis to \<10mm. PR:30% or more decrease in SLD of target lesion, taking as reference baseline SLD. PD:20% or more increase in the SLD of target lesions relative to baseline or smallest SLD (nadir) recorded since first dose. In addition, also demonstrate absolute increase of at least 5mm (\>=5mm) relative to baseline or smallest SLD (nadir) recorded since first dose. |
| Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Weeks 12 and 24 | Tumor response was evaluated according to RECIST version 1.1, and disease control was defined as confirmed CR, confirmed PR, or stable disease (SD). CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. SD= when neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD is observed, taking as reference the smallest sum diameters while on study. Intracranial assessment was only performed for participants CNS metastases. Results presented here were based on independent central review. |
| Time to Progression on the Last Prior Therapy (Phase 2) | From first dose of study treatment to the date of progression (maximum of 7.5 years for Phase 2) | TTP on the last prior therapy was defined as time from the first dose date of the last prior treatment regimen to the date of progression. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. |
| Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | From first dose of study treatment to the first documentation of objective PD (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Time to progression (TTP) was defined as the time from the first dose of study treatment to the first documentation of objective PD. Intracranial TTP was defined as the time from the first dose of study treatment to the date of the first documentation of objective progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. Results presented here were based on independent central review. |
| Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2) | From first dose of study treatment until first event of CNS progression (maximum of 7.5 years for Phase 2) | Probability of first event being CNS progression, non-CNS progression, or death was evaluated with competing risk approach by estimating cumulative incidence functions (range: 0-1) relative to analysis set. Time to first event being Competing Event (either CNS progression or non CNS progression or Death) = time from first dose until date of that specific event. Participants not known to have any of Competing Events were censored on date they were last assessed for disease status for PFS. Participants who presented one type of event were counted as competing cause of failure for analysis of other type of events. For each type of event, cumulative incidence function corresponding to nearest time point preceding 1 year is presented. PD:20% or more increase in SLD of target lesion relative to baseline or smallest SLD (nadir) recorded since first dose. SLD must demonstrate absolute increase of atleast 5mm(\>=5 mm) relative to baseline or smallest SLD (nadir) recorded since first dose. |
| Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | From first dose of study treatment to first documentation of objective PD or death due to any cause, whichever came first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | PFS was defined as the time from the first dose of study treatment to the first documentation of objective PD or to death on study due to any cause, whichever came first. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. Results presented here were based on independent central review. |
| Overall Survival (Phase 2 and DDI Substudy) | From first dose of study treatment until date of death (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | OS was defined as the time from first dose to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method. |
| Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Maximum observed plasma concentration (Cmax) of PF-06463922 was observed directly from data. |
| Time for Cmax (Tmax) of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Tmax of PF-06463922 was observed directly from data as time of first occurrence. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 | AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Tau refers to the dosing interval, and it equals to 24 hours for QD dosing which was adopted in Phase 2. AUCtau was determined using linear/log trapezoidal method. |
| Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. |
| Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 | Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf\*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase. |
| Terminal Half-Life of PF-06463922 (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 | Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. |
| Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Rac was calculated as Day 15 AUCtau/Day -7 AUCtau, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen which was adopted in Phase 2). |
| Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15 | Rss was calculated as Day 15 AUCtau/Day -7 AUCinf, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen which was adopted in Phase 2), and AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. |
| Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2) | Screening (up to 28 days) | Plasma CNA samples were analyzed for ALK kinase domain mutations by Next Generation Sequencing (NGS). Number of participants with one or more ALK mutations is presented. |
| Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2) | Screening (up to 28 days) | Tumor tissues from archived tissue specimens and/or a de novo biopsy were analyzed for ALK kinase domain mutations. Number of participants with one or more ALK mutations is presented. |
| Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ)-C30 (version 3.0) consists of 30 questions assessing 5 functional domains (physical, role, emotional, cognitive and social), global quality of life (QoL), disease/treatment related symptoms (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea), and the perceived financial impact of disease. Each scale was transformed to a range of 0 to 100 using standard EORTC algorithm. For global QoL and functional scales, higher score indicate better performance, and improvement was defined as an increase of at least 10 points, worsening was defined as a decrease of at least 10 points. For symptom scales, higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. |
| Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. |
| Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | AE: any untoward medical occurrence in clinical investigation participant administered a product or medical device, regardless of causal relationship to study treatment. Treatment-emergent AEs (TEAEs): AEs which occurred for first time during effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs): any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of ability to conduction normal life function). AEs included SAEs and non-serious AEs. Severity was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.Grade1: mild, Grade2: moderate, Grade3: severe, Grade4: Life threatening consequences; urgent intervention indicated, Grade 5: death related to AE. |
| Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. Hematology parameters with any abnormalities were reported in this outcome measure. |
| Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Chemistry evaluation included alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), blood bilirubin, creatine phosphokinase (CPK), creatinine, gamma-glutamyl transferase (GGT), calcium, sodium, potassium, magnesium, albumin, glucose (non-fasted), albumin, phosphorus or phosphate, serum amylase and lipase. |
| Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Coagulation evaluation included activated partial thromboplastin time, international normalized ratio (INR), and prothrombin time. Lipid evaluation included Cholesterol and triglycerides. |
| Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position. Body weight was also measured. |
| Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Left Ventricular Ejection Fraction (LVEF) was determined by echocardiogram. Baseline was defined as the measurement prior to the first dose of study treatment. |
| Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Triplicate 12-lead electrocardiograms (ECGs) were performed approximately 2 minutes apart to determine mean QTc interval (QT interval corrected for heart rate). QT interval was corrected for heart rate using Fridericia's formula to provide QTcF. Absolute values and changes from baseline were summarized according to pre-defined criteria. Baseline was defined as the last evaluation on or prior to the first dose of study treatment. |
| Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years) | The Beck Depression Inventory (BDI)-II is a 21-item self-report scale, with each item rated by participants on a 4-point scale (ranging from 0-3, where 0 indicated lowest depression and 3 indicated severe depression). The scale includes items capturing mood, (loss of pleasure, sadness, and irritability), suicidal ideation, and cognitive signs (punitive thoughts, self-criticism, self-dislike, pessimism, and poor concentration) as well as somatic signs (appetite, sleep, fatigue and libido). Scores were obtained by adding up the total points from the series of answers. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs are as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression. |
| Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years) | The Detection Test is a measure of psychomotor function and uses a well validated simple reaction time paradigm with playing card stimuli. In this test, the on-screen instructions ask: Has the card turned over?. A playing card is presented face down in the center of the screen. The card flips over so it is face up. As soon as the card flips over the participant must press Yes. The participant is encouraged to work as quickly as they can and be as accurate as possible. The speed and accuracy of each response are recorded and mean of the log10 transformed reaction times for correct responses is calculated. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle. |
| Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years) | The Identification Test is a measure of visual attention and uses a well validated choice reaction time paradigm with playing card stimuli. In this task, the playing cards are all red or black jokers. The on-screen instructions ask: Is the card red?. A playing card is presented face down in the center of the screen. The card flips over so it is face up. As soon as it flips over the participant must decide whether the card is red or not. If it is red the participant should press Yes, and if it is not red the participant should press No. The participant is encouraged to work as quickly and accurately as possible. The speed and accuracy of each response are recorded and mean of the log10 transformed reaction times for correct responses is calculated. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle. |
| Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years) | The One Back Test is a measure of working memory and uses a well validated n back paradigm with playing cards. In this task, the on-screen instructions ask: Is the previous card the same?. A playing card is presented in the center of the screen. The participant must decide whether the card is the same as the previous card. If it is the same the participant should press Yes, and if not press No. The participant is encouraged to work as quickly and accurately as possible. The speed and accuracy of each response are recorded, mean of the log10 transformed reaction times for correct responses is used to demonstrate speed of performance, and the arcsine transformation of the square root of the proportion of correct responses is used to demonstrate accuracy. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle. |
| Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years) | The International Shopping List task is a measure of verbal learning and uses a well validated list learning paradigm administered using a computer. High frequencies, high imagery, concrete nouns (items from a shopping list) were read to the participant at the rate of one word every 2 seconds. Once all 12 words had been read, the participant was asked to recall as many of the words as quickly as possible. The words recalled by the participant were marked on the computer screen. When the participant could recall no more words, the same list was read again. The words recalled by the participant were recorded. This was then repeated a third time. Total number of correct responses on 3 consecutive trials at a single assessment was recorded. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle. |
| Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years) | This test was performed in the same way as the International Shopping List Test, with the exception that, the delayed recall condition required the participant to recall the words from the list 15 30 minutes later without having the list read again. During the recognition condition, the qualified personnel read a shopping list item that may or may not have been on the original list and the participant had to respond either affirmatively (if the item was on the original list) or negatively (if it was not). Total number of correct responses made in remembering the word list after a delay was recorded. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle. |
| Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | PR Interval was determined by ECG measurement. PR interval had following categories: change from baseline\>=25 percent, 40 to \<60 milliseconds (msec), 60 to \<80 msec and \>=80 msec. Baseline was defined as the average of the triplicate measurements prior to the first dose of study drug. |
| Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2) | The Columbia Suicide Severity Rating Scale (C-SSRS) was used to analyze participants' suicidal ideation and behavior, and it is a unique, simple and short method of assessing both behavior and ideation that tracks all suicidal events and provides a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation and deterrents), all of which are significantly predictive of completed suicide. Maximum score of 4 or 5 indicates maximum suicidal ideation and minimum score of 0 indicates no suicidal ideation. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours post-dose on Day -7 for all other groups. | Tau refers to the dosing interval, and it equals to 12 or 24 hours for BID or QD dosing, respectively. AUCtau was determined using linear/log trapezoidal method. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study) | Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 milliliter (mm) on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 percent (%) or more decrease in sum of lesion dimensions (SLD) of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review. |
Countries
Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Singapore, South Korea, Spain, Switzerland, Taiwan, United States
Participant flow
Pre-assignment details
A total of 364 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| 10 mg QD (Phase 1) PF-06463922 10 mg was orally given once daily (QD) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 3 |
| 25 mg QD (Phase 1) PF-06463922 25 mg was orally given QD in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. Midazolam 2 mg was orally given QD on Day -7 and Cycle 1 Day 15. | 3 |
| 50 mg QD (Phase 1) PF-06463922 50 mg was orally given QD on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 3 |
| 75 mg QD (Phase 1) PF-06463922 75 mg was orally given QD on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 12 |
| 100 mg QD (Phase 1) PF-06463922 100 mg was orally given QD on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 17 |
| 150 mg QD (Phase 1) PF-06463922 150 mg was orally given QD in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. Midazolam 2 mg was orally given QD on Day -7 and Cycle 1 Day 15. | 3 |
| 200 mg QD (Phase 1) PF-06463922 200 mg was orally given QD on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 3 |
| 35 mg BID (Phase 1) PF-06463922 35 mg was orally given twice daily (BID) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 3 |
| 75 mg BID (Phase 1) PF-06463922 75 mg was orally given BID on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 3 |
| 100 mg BID (Phase 1) PF-06463922 100 mg was orally given BID on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 4 |
| EXP-1 (Phase 2) Treatment-naïve participants with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) with or without asymptomatic central nervous system (CNS) metastases were given PF-06463922 100 mg orally QD on Day -7 (only participants scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 30 |
| EXP-2 (Phase 2) Participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after only crizotinib therapy were given PF-06463922 100 mg orally QD on Day -7 (only for participants scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 27 |
| EXP-3 (Phase 2) Participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after crizotinib therapy and 1 or 2 prior regimens of chemotherapy given before or after crizotinib therapy, or participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after 1 ALK inhibitor therapy other than crizotinib with or without any number of prior chemotherapy regimens in any disease setting were given PF-06463922 100 mg orally QD on Day -7 (only for participants scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 60 |
| EXP-4 (Phase 2) Participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after 2 prior lines of ALK inhibitor therapies were given PF-06463922 100 mg orally QD on Day -7 (only for participants scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 65 |
| EXP-5 (Phase 2) Participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after 3 prior lines of ALK inhibitor therapies were given PF-06463922 100 mg orally QD on Day -7 (only for participant scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 46 |
| EXP-6 (Phase 2) Participants with advanced ROS1-positive NSCLC who were treatment naïve or had any number of prior cancer therapies with or without asymptomatic CNS metastases were given PF-06463922 100 mg orally QD on Day -7 (only for participants scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. | 47 |
| Japan Lead-In Cohort (LIC) Few Japanese participants were given PF-06463922 100 mg orally once daily (QD) in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal to evaluate safety of PF-06463922 in Japanese participants, in order to support inclusion of Japanese participants in Phase 2. | 3 |
| Drug-drug Interaction (DDI) Sub-study Participants with advanced ALK positive or ROS1-positive NSCLC who were treatment naïve or had any number of prior cancer therapies with or without asymptomatic CNS metastases were administered a single dose of a probe substrate alone on Day -2. Participants were given PF-06463922 100 mg orally QD starting on Cycle1 Day 1 and along with probe substrate on Day 15 Cycle 1. | 32 |
| Total | 364 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 2 | 3 | 6 | 9 | 3 | 2 | 3 | 2 | 2 | 8 | 13 | 25 | 46 | 37 | 22 | 1 | 17 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 4 | 0 | 1 |
| Overall Study | Other | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 3 | 8 | 3 | 2 | 3 | 0 | 2 |
| Overall Study | Participant refused further follow-up | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 7 | 8 | 3 | 11 | 0 | 6 |
Baseline characteristics
| Characteristic | 10 mg QD (Phase 1) | 25 mg QD (Phase 1) | 50 mg QD (Phase 1) | 75 mg QD (Phase 1) | 100 mg QD (Phase 1) | 150 mg QD (Phase 1) | 200 mg QD (Phase 1) | 35 mg BID (Phase 1) | 75 mg BID (Phase 1) | 100 mg BID (Phase 1) | EXP-1 (Phase 2) | EXP-2 (Phase 2) | EXP-3 (Phase 2) | EXP-4 (Phase 2) | EXP-5 (Phase 2) | EXP-6 (Phase 2) | Japan Lead-In Cohort (LIC) | Drug-drug Interaction (DDI) Sub-study | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 years | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 7 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 5 Participants | 14 Participants | 19 Participants | 13 Participants | 12 Participants | 2 Participants | 5 Participants | 91 Participants |
| Age, Customized <18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 45-64 years | 1 Participants | 1 Participants | 3 Participants | 6 Participants | 9 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 18 Participants | 13 Participants | 34 Participants | 37 Participants | 26 Participants | 27 Participants | 1 Participants | 20 Participants | 204 Participants |
| Age, Customized >=65 years | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants | 9 Participants | 12 Participants | 9 Participants | 7 Participants | 8 Participants | 0 Participants | 7 Participants | 69 Participants |
| Race/Ethnicity, Customized ASIAN | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 17 Participants | 10 Participants | 23 Participants | 23 Participants | 14 Participants | 16 Participants | 3 Participants | 11 Participants | 124 Participants |
| Race/Ethnicity, Customized BLACK | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Others | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 13 Participants |
| Race/Ethnicity, Customized Unspecified | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 10 Participants | 7 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 31 Participants |
| Race/Ethnicity, Customized WHITE | 2 Participants | 2 Participants | 3 Participants | 7 Participants | 13 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 10 Participants | 13 Participants | 25 Participants | 32 Participants | 27 Participants | 25 Participants | 0 Participants | 21 Participants | 190 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 7 Participants | 11 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 13 Participants | 17 Participants | 38 Participants | 37 Participants | 25 Participants | 27 Participants | 2 Participants | 15 Participants | 206 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants | 5 Participants | 6 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 17 Participants | 10 Participants | 22 Participants | 28 Participants | 21 Participants | 20 Participants | 1 Participants | 17 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 2 / 3 | 3 / 3 | 6 / 12 | 9 / 17 | 3 / 3 | 2 / 3 | 3 / 3 | 2 / 3 | 2 / 4 | 1 / 3 | 8 / 30 | 13 / 27 | 25 / 60 | 46 / 65 | 37 / 46 | 22 / 47 | 17 / 32 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 12 / 12 | 17 / 17 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 30 / 30 | 27 / 27 | 59 / 60 | 65 / 65 | 45 / 46 | 47 / 47 | 32 / 32 |
| serious Total, serious adverse events | 3 / 3 | 2 / 3 | 1 / 3 | 6 / 12 | 10 / 17 | 3 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 2 / 4 | 1 / 3 | 15 / 30 | 11 / 27 | 34 / 60 | 31 / 65 | 23 / 46 | 21 / 47 | 13 / 32 |
Outcome results
Primary
Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1
DLT: any of following adverse events (AEs) attributable to PF-06463922: (1) hematologic: grade 4 neutropenia for \>7 days; febrile neutropenia; grade\>=3 neutropenic infection; grade\>=3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade\>=3 pancreatitis; grade\>=3 toxicities (excluding grade \>=3 laboratory abnormalities not requiring dose modifications) persisting after optimal treatment with standard medical therapy; symptomatic grade \>=3 QT interval corrected for heart rate (QTc) prolongation, or asymptomatic grade \>=3 prolongation that had been confirmed by repeat testing, re-evaluation by qualified person, persisted after correction of reversible causes; \>=20% decrease from baseline in left ventricular ejection fraction (LVEF); (3) other: failure to deliver at least 16 out of 21 prescribed daily total dose due to toxicities attributable to study drug; failure to restart dosing after 21 days (1 cycle) delay due to toxicity attributable to study drug.
Time frame: Cycle 1 (21 days)
Population: Maximum Tolerated Dose (MTD) evaluable population included all enrolled participants who received at least 75% of the planned PF-06463922 doses in Cycle 1. Participants who received less than 75% of the planned PF-06463922 doses in Cycle 1 due to DLT were also considered evaluable for MTD. Here, Overall Number Analyzed signifies participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 8 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 8 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 2 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 3 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | With DLT | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | Data missing | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 | No DLT | 2 Participants |
Primary
Percentage of Participants With Overall and Intracranial Objective Response (Phase 2)
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 milliliter (mm) on Target Lesions electronic case report form (eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 percent (%) or more decrease in sum of lesion dimensions (SLD) of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review.
Time frame: 3 years
Population: The intent-to-treat (ITT) analysis set was used for overall response assessment, and included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; participants with central nervous system (CNS) metastases in the ITT analysis set were used for intracranial response assessment. Here, Number Analyzed signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Objective response | 90.0 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Intracranial objective response | 75.0 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Objective response | 74.1 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Intracranial objective response | 58.8 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Objective response | 50.8 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Intracranial objective response | 62.5 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Objective response | 41.5 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Intracranial objective response | 55.6 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Objective response | 34.8 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Intracranial objective response | 39.5 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Objective response | 36.2 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2) | Intracranial objective response | 56.0 Percentage of participants |
Secondary
Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for midazolam included all participants who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. Here, 'Number Analyzed' signifies participants evaluable for specified rows
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of Midazolam (Phase 1) | Day -7 | 36.68 L/hr | Geometric Coefficient of Variation 43 |
| 10 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of Midazolam (Phase 1) | Cycle 1 Day 15 | 93.86 L/hr | Geometric Coefficient of Variation 18 |
| 25 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of Midazolam (Phase 1) | Day -7 | NA L/hr | — |
| 25 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of Midazolam (Phase 1) | Cycle 1 Day 15 | 124.2 L/hr | Geometric Coefficient of Variation 29 |
Secondary
Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 13.27 L/hr | Geometric Coefficient of Variation 26 |
| 25 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 14.72 L/hr | Geometric Coefficient of Variation 29 |
| 50 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 14.84 L/hr | Geometric Coefficient of Variation 39 |
| 75 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 17.66 L/hr | Geometric Coefficient of Variation 48 |
| 100 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 19.52 L/hr | Geometric Coefficient of Variation 30 |
| 150 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 24.37 L/hr | Geometric Coefficient of Variation 9 |
| 200 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA L/hr | — |
| 35 mg BID (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA L/hr | — |
| 75 mg BID (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 20.99 L/hr | Geometric Coefficient of Variation 35 |
| 100 mg BID (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 22.37 L/hr | Geometric Coefficient of Variation 47 |
Secondary
Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liter/hour (L/hr) | — |
| 25 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liter/hour (L/hr) | — |
| 50 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 9.788 Liter/hour (L/hr) | Geometric Coefficient of Variation 79 |
| 75 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 12.14 Liter/hour (L/hr) | Geometric Coefficient of Variation 25 |
| 100 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 10.90 Liter/hour (L/hr) | Geometric Coefficient of Variation 61 |
| 150 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liter/hour (L/hr) | — |
| 200 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liter/hour (L/hr) | — |
| 35 mg BID (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 15.83 Liter/hour (L/hr) | Geometric Coefficient of Variation 56 |
Secondary
Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2) | Day -7 | 11.01 Liter/hour | Geometric Coefficient of Variation 35 |
| 10 mg QD (Phase 1) | Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2) | Cycle 1 Day 15 | 17.70 Liter/hour | Geometric Coefficient of Variation 39 |
Secondary
Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)
Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf\*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for midazolam included all participants who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1) | Day -7 | 229.0 Liters | Geometric Coefficient of Variation 7 |
| 10 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1) | Cycle 1 Day 15 | 404.4 Liters | Geometric Coefficient of Variation 51 |
| 25 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1) | Day -7 | NA Liters | — |
| 25 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1) | Cycle 1 Day 15 | 702.2 Liters | Geometric Coefficient of Variation 100 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)
Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf\*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liters (L) | — |
| 25 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liters (L) | — |
| 50 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 367.9 Liters (L) | Geometric Coefficient of Variation 54 |
| 75 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 356.3 Liters (L) | Geometric Coefficient of Variation 39 |
| 100 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 307.8 Liters (L) | Geometric Coefficient of Variation 41 |
| 150 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liters (L) | — |
| 200 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Liters (L) | — |
| 35 mg BID (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) | 378.3 Liters (L) | Geometric Coefficient of Variation 54 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2)
Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf\*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2) | 351.5 Liters | Geometric Coefficient of Variation 37 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)
AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for midazolam included all participants who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1) | Day -7 | 54.53 ng*hr/mL | Geometric Coefficient of Variation 43 |
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1) | Cycle 1 Day 15 | 21.32 ng*hr/mL | Geometric Coefficient of Variation 18 |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1) | Day -7 | NA ng*hr/mL | — |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1) | Cycle 1 Day 15 | 16.09 ng*hr/mL | Geometric Coefficient of Variation 29 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)
AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | NA ng*hr/mL | — |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | NA ng*hr/mL | — |
| 50 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | 7663 ng*hr/mL | Geometric Coefficient of Variation 79 |
| 75 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | 8236 ng*hr/mL | Geometric Coefficient of Variation 25 |
| 100 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | 18340 ng*hr/mL | Geometric Coefficient of Variation 61 |
| 150 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | NA ng*hr/mL | — |
| 200 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | NA ng*hr/mL | — |
| 35 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) | 6318 ng*hr/mL | Geometric Coefficient of Variation 56 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2)
AUCinf was calculated as AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, 'Overall Number of Participants Analyzed' signifies participants analyzed for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2) | 9088 ng*hour/mL | Geometric Coefficient of Variation 35 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)
Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of midazolam was determined using linear/log trapezoidal method. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for midazolam included all participants who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1) | Day -7 | 51.30 ng*hr/mL | Geometric Coefficient of Variation 47 |
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1) | Cycle 1 Day 15 | 20.43 ng*hr/mL | Geometric Coefficient of Variation 18 |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1) | Day -7 | 36.49 ng*hr/mL | Geometric Coefficient of Variation 20 |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1) | Cycle 1 Day 15 | 14.44 ng*hr/mL | Geometric Coefficient of Variation 25 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Tau refers to the dosing interval, and it equals to 12 or 24 hours for BID or QD dosing, respectively. AUCtau was determined using linear/log trapezoidal method.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 752.1 ng*hr/mL | Geometric Coefficient of Variation 26 |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1701 ng*hr/mL | Geometric Coefficient of Variation 29 |
| 50 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 3367 ng*hr/mL | Geometric Coefficient of Variation 39 |
| 75 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 4107 ng*hr/mL | Geometric Coefficient of Variation 53 |
| 100 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 5121 ng*hr/mL | Geometric Coefficient of Variation 30 |
| 150 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 6157 ng*hr/mL | Geometric Coefficient of Variation 9 |
| 200 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA ng*hr/mL | — |
| 35 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA ng*hr/mL | — |
| 75 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 3574 ng*hr/mL | Geometric Coefficient of Variation 35 |
| 100 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 4058 ng*hr/mL | Geometric Coefficient of Variation 33 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)
Tau refers to the dosing interval, and it equals to 12 or 24 hours for BID or QD dosing, respectively. AUCtau was determined using linear/log trapezoidal method.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 488.2 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| 25 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 1387 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| 50 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Nanogram*hour/milliliter (ng*hr/mL) | — |
| 75 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 3990 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 55 |
| 100 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 5110 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| 150 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 7474 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 73 |
| 200 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 11410 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| 35 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 982.4 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 9 |
| 75 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 2996 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
| 100 mg BID (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) | 2925 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 47 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2)
Tau refers to the dosing interval, and it equals to 24 hours for QD dosing which was adopted in Phase 2. AUCtau was determined using linear/log trapezoidal method.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2) | Day -7 | 5308 ng*hour/mL | Geometric Coefficient of Variation 36 |
| 10 mg QD (Phase 1) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2) | Cycle 1 Day 15 | 5650 ng*hour/mL | Geometric Coefficient of Variation 39 |
Secondary
Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1)
In Phase 1, the MMSE was collected to assess mental status. The MMSE is a 30 item questionnaire that tests 5 areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30 and minimum score is 0. Highest score indicates no cognitive impairment, lowest score indicates severe cognitive impairment. The MMSE was removed under Amendment 6 of the study protocol, and not required for Phase 2, as the tool was not considered meaningful for assessment of cognitive function.
Time frame: Baseline, Day 1 of Cycle 1-52, and end of treatment (up to 3 years)
Population: MMSE assessment evaluable analysis set included all participants in the safety analysis set (all participants who received at least 1 dose of PF-06463922) who completed a baseline and at least 1 post-baseline assessment. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure. Here, Number Analyzed signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | 2.0 Units on a scale | Standard Deviation 0 |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 2.0 Units on a scale | — |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 1 Day 1 | 1.0 Units on a scale | Standard Deviation 1.41 |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | End of treatment | -8.0 Units on a scale | — |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 2.5 Units on a scale | Standard Deviation 2.12 |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 2.0 Units on a scale | — |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | -5.0 Units on a scale | — |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | -4.0 Units on a scale | — |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 0.5 Units on a scale | Standard Deviation 3.54 |
| 10 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | 5.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 38 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 41 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 42 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 43 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 33 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 35 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 18 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 34 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 21 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 52 Day 1 | 1.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 51 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 50 Day 1 | -3.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 49 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 48 Day 1 | -3.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 47 Day 1 | 0.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 46 Day 1 | 0.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 45 Day 1 | 1.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 40 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 32 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 31 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | -0.3 Units on a scale | Standard Deviation 0.58 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 39 Day 1 | 0.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | 0.3 Units on a scale | Standard Deviation 0.58 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | -1.5 Units on a scale | Standard Deviation 2.12 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 44 Day 1 | 1.0 Units on a scale | — |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | -2.0 Units on a scale | Standard Deviation 2.83 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | 0.0 Units on a scale | Standard Deviation 1.41 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 36 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 15 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 37 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | 0.5 Units on a scale | Standard Deviation 0.71 |
| 25 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | 0.0 Units on a scale | — |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 1.0 Units on a scale | Standard Deviation 1.41 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | End of treatment | 0.7 Units on a scale | Standard Deviation 1.15 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 1.5 Units on a scale | Standard Deviation 2.12 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | 0.0 Units on a scale | — |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 1.5 Units on a scale | Standard Deviation 2.12 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | 1.5 Units on a scale | Standard Deviation 2.12 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 2.0 Units on a scale | — |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | 0.0 Units on a scale | — |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 1 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 50 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 1.5 Units on a scale | Standard Deviation 2.12 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | 0.8 Units on a scale | Standard Deviation 1.79 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 37 Day 1 | -1.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 32 Day 1 | 1.3 Units on a scale | Standard Deviation 2.31 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 39 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | 0.8 Units on a scale | Standard Deviation 1.79 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 48 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | 0.0 Units on a scale | Standard Deviation 1.41 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 47 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | 0.6 Units on a scale | Standard Deviation 1.95 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 46 Day 1 | -1.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | -0.3 Units on a scale | Standard Deviation 3.2 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | -0.4 Units on a scale | Standard Deviation 0.89 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | 0.8 Units on a scale | Standard Deviation 1.79 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 45 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | -0.4 Units on a scale | Standard Deviation 2.7 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 31 Day 1 | 1.0 Units on a scale | Standard Deviation 2.65 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | 0.8 Units on a scale | Standard Deviation 1.79 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 1 Day 1 | -0.9 Units on a scale | Standard Deviation 2.27 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | -0.1 Units on a scale | Standard Deviation 2.34 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 0.3 Units on a scale | Standard Deviation 1.41 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | 0.8 Units on a scale | Standard Deviation 1.5 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | -0.1 Units on a scale | Standard Deviation 1.21 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | 0.5 Units on a scale | Standard Deviation 1.73 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | -0.6 Units on a scale | Standard Deviation 1.85 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 38 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | 1.0 Units on a scale | Standard Deviation 2 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | 0.3 Units on a scale | Standard Deviation 1.7 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 44 Day 1 | -1.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 15 Day 1 | -1.7 Units on a scale | Standard Deviation 5.43 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 42 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 36 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | -1.1 Units on a scale | Standard Deviation 1.81 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 33 Day 1 | 1.3 Units on a scale | Standard Deviation 2.31 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | -0.2 Units on a scale | Standard Deviation 2.49 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 35 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 18 Day 1 | 0.8 Units on a scale | Standard Deviation 1.79 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 41 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 34 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | 0.8 Units on a scale | Standard Deviation 1.79 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | End of treatment | -2.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | 0.0 Units on a scale | Standard Deviation 1.41 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 40 Day 1 | -1.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | -0.6 Units on a scale | Standard Deviation 2.19 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 43 Day 1 | 0.0 Units on a scale | — |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 21 Day 1 | 0.0 Units on a scale | Standard Deviation 1.41 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | -1.0 Units on a scale | Standard Deviation 2.31 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 0.3 Units on a scale | Standard Deviation 1.25 |
| 75 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | 0.4 Units on a scale | Standard Deviation 1.52 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | -0.2 Units on a scale | Standard Deviation 1.53 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 39 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | -0.2 Units on a scale | Standard Deviation 1.72 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | 0.1 Units on a scale | Standard Deviation 1.81 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 41 Day 1 | 0.0 Units on a scale | — |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 36 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | 0.1 Units on a scale | Standard Deviation 1.17 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | -0.6 Units on a scale | Standard Deviation 2.65 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 42 Day 1 | 0.0 Units on a scale | — |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | 0.1 Units on a scale | Standard Deviation 1.45 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 31 Day 1 | 0.7 Units on a scale | Standard Deviation 0.82 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 40 Day 1 | 0.0 Units on a scale | — |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 15 Day 1 | 0.1 Units on a scale | Standard Deviation 1.36 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | -0.4 Units on a scale | Standard Deviation 2.77 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | -0.1 Units on a scale | Standard Deviation 2.67 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | -0.2 Units on a scale | Standard Deviation 2.33 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | -0.2 Units on a scale | Standard Deviation 1.99 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | 0.5 Units on a scale | Standard Deviation 2.22 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 1 Day 1 | 0.8 Units on a scale | Standard Deviation 1.39 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | 0.3 Units on a scale | Standard Deviation 2.1 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | 0.4 Units on a scale | Standard Deviation 0.55 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 38 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | End of treatment | -2.3 Units on a scale | Standard Deviation 5.19 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 32 Day 1 | 0.4 Units on a scale | Standard Deviation 0.55 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 33 Day 1 | 0.5 Units on a scale | Standard Deviation 0.58 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 21 Day 1 | 0.1 Units on a scale | Standard Deviation 2.09 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 0.0 Units on a scale | Standard Deviation 1.79 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | -0.9 Units on a scale | Standard Deviation 2.27 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 35 Day 1 | 0.3 Units on a scale | Standard Deviation 0.5 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | 0.0 Units on a scale | Standard Deviation 1.47 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | 0.1 Units on a scale | Standard Deviation 1.81 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | 0.3 Units on a scale | Standard Deviation 0.79 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | -0.1 Units on a scale | Standard Deviation 0.88 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 0.4 Units on a scale | Standard Deviation 0.9 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 0.3 Units on a scale | Standard Deviation 0.9 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 37 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | 0.2 Units on a scale | Standard Deviation 1.52 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 18 Day 1 | 0.0 Units on a scale | Standard Deviation 1.73 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 0.2 Units on a scale | Standard Deviation 1.34 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | 0.7 Units on a scale | Standard Deviation 0.76 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | 0.7 Units on a scale | Standard Deviation 2.12 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | 0.6 Units on a scale | Standard Deviation 0.74 |
| 100 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 34 Day 1 | 0.3 Units on a scale | Standard Deviation 0.5 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | 1.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | 6.0 Units on a scale | Standard Deviation 8.49 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | -3.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 18 Day 1 | -2.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | 0.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | 0.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | 0.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | -1.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | -2.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | -1.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 4.7 Units on a scale | Standard Deviation 8.08 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | 5.0 Units on a scale | Standard Deviation 8.49 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | 2.0 Units on a scale | Standard Deviation 6.24 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 4.7 Units on a scale | Standard Deviation 8.14 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 4.3 Units on a scale | Standard Deviation 5.86 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 4.7 Units on a scale | Standard Deviation 8.33 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 3.0 Units on a scale | Standard Deviation 7.81 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | 6.0 Units on a scale | Standard Deviation 8.49 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | 6.5 Units on a scale | Standard Deviation 9.19 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | 7.0 Units on a scale | Standard Deviation 8.49 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | 6.5 Units on a scale | Standard Deviation 9.19 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | 5.5 Units on a scale | Standard Deviation 7.78 |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | 1.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | -1.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | -2.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | 0.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | 0.0 Units on a scale | — |
| 150 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 31 Day 1 | 0.0 Units on a scale | — |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | 1.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 37 Day 1 | 3.5 Units on a scale | Standard Deviation 4.95 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | 1.5 Units on a scale | Standard Deviation 4.95 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 40 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | 3.0 Units on a scale | Standard Deviation 2.83 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 45 Day 1 | 1.0 Units on a scale | — |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 3.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 44 Day 1 | 3.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 35 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 31 Day 1 | 3.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 32 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | 2.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 15 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | 3.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 36 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | 6.0 Units on a scale | — |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 2.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 39 Day 1 | 3.5 Units on a scale | Standard Deviation 4.95 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | 1.5 Units on a scale | Standard Deviation 6.36 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 38 Day 1 | 3.0 Units on a scale | Standard Deviation 2.83 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 41 Day 1 | 1.5 Units on a scale | Standard Deviation 6.36 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 42 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | 6.0 Units on a scale | — |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 0.5 Units on a scale | Standard Deviation 6.36 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 18 Day 1 | 3.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 43 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 34 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | 2.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | 3.5 Units on a scale | Standard Deviation 4.95 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | -0.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 33 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | 3.5 Units on a scale | Standard Deviation 3.54 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | 2.5 Units on a scale | Standard Deviation 4.95 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | 3.0 Units on a scale | Standard Deviation 2.83 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 21 Day 1 | 4.0 Units on a scale | Standard Deviation 4.24 |
| 200 mg QD (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | 3.0 Units on a scale | Standard Deviation 2.83 |
| 35 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 15 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 1 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 32 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | -1.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 21 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | End of treatment | -15.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 33 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 34 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 36 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 35 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 38 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | 0.0 Units on a scale | — |
| 75 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | 0.0 Units on a scale | — |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 14 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 28 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 20 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 7 Day 1 | -0.7 Units on a scale | Standard Deviation 1.15 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 19 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 13 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 9 Day 1 | -0.3 Units on a scale | Standard Deviation 0.58 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | End of treatment | 0.0 Units on a scale | — |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 3 Day 1 | -1.0 Units on a scale | Standard Deviation 1 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 8 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 27 Day 1 | -1.0 Units on a scale | Standard Deviation 1.41 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 18 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 4 Day 1 | -0.7 Units on a scale | Standard Deviation 1.15 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 33 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 34 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 17 Day 1 | -1.3 Units on a scale | Standard Deviation 1.53 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 11 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 35 Day 1 | 0.0 Units on a scale | — |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 5 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 16 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 25 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 10 Day 1 | -1.7 Units on a scale | Standard Deviation 1.53 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 31 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 36 Day 1 | 0.0 Units on a scale | — |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 32 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 26 Day 1 | -0.3 Units on a scale | Standard Deviation 0.58 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 24 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 15 Day 1 | -0.3 Units on a scale | Standard Deviation 0.58 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 30 Day 1 | -1.0 Units on a scale | Standard Deviation 1 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 1 Day 1 | 0.0 Units on a scale | — |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 23 Day 1 | -2.3 Units on a scale | Standard Deviation 4.04 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 12 Day 1 | -0.7 Units on a scale | Standard Deviation 0.58 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 29 Day 1 | 0.0 Units on a scale | Standard Deviation 0 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 22 Day 1 | -0.3 Units on a scale | Standard Deviation 0.58 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 6 Day 1 | -1.3 Units on a scale | Standard Deviation 2.31 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 2 Day 1 | -0.3 Units on a scale | Standard Deviation 1.15 |
| 100 mg BID (Phase 1) | Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) | Cycle 21 Day 1 | -0.5 Units on a scale | Standard Deviation 0.71 |
Secondary
Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2)
The Beck Depression Inventory (BDI)-II is a 21-item self-report scale, with each item rated by participants on a 4-point scale (ranging from 0-3, where 0 indicated lowest depression and 3 indicated severe depression). The scale includes items capturing mood, (loss of pleasure, sadness, and irritability), suicidal ideation, and cognitive signs (punitive thoughts, self-criticism, self-dislike, pessimism, and poor concentration) as well as somatic signs (appetite, sleep, fatigue and libido). Scores were obtained by adding up the total points from the series of answers. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs are as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression.
Time frame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 20 Day 1 | -5.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 6 Day 1 | -3.51 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 16 Day 1 | -1.75 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 26 Day 1 | -5.50 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 10 Day 1 | -3.09 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 5 Day 1 | -4.47 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | End of treatment | -4.77 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 22 Day 1 | -2.93 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 4 Day 1 | -3.84 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 14 Day 1 | -3.81 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 18 Day 1 | -4.49 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 12 Day 1 | -3.95 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 2 Day 1 | -2.59 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 24 Day 1 | -7.31 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 3 Day 1 | -3.34 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 8 Day 1 | -4.17 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 24 Day 1 | -5.63 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 8 Day 1 | -4.86 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 6 Day 1 | -4.25 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 4 Day 1 | -4.10 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 5 Day 1 | -3.96 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 18 Day 1 | -7.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 10 Day 1 | -4.92 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 22 Day 1 | -4.63 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 16 Day 1 | -4.61 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 3 Day 1 | -3.18 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 14 Day 1 | -5.80 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | End of treatment | -0.73 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 20 Day 1 | -5.17 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 12 Day 1 | -5.60 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 2 Day 1 | -3.27 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 22 Day 1 | -2.36 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 3 Day 1 | -3.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 5 Day 1 | -2.75 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 6 Day 1 | -3.31 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 14 Day 1 | -2.58 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 16 Day 1 | -2.15 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 24 Day 1 | -2.88 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 26 Day 1 | -3.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | End of treatment | -2.55 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 2 Day 1 | -2.26 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 4 Day 1 | -2.59 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 8 Day 1 | -2.26 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 10 Day 1 | -1.94 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 12 Day 1 | -0.72 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 18 Day 1 | -1.96 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 20 Day 1 | -1.82 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 24 Day 1 | -3.89 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 2 Day 1 | -2.17 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 20 Day 1 | -3.63 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 10 Day 1 | -4.27 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 5 Day 1 | -3.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 4 Day 1 | -1.95 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 3 Day 1 | -3.10 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 12 Day 1 | -4.80 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | End of treatment | -3.22 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 26 Day 1 | -4.30 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 14 Day 1 | -4.29 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 8 Day 1 | -4.06 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 16 Day 1 | -4.65 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 6 Day 1 | -3.79 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 22 Day 1 | -5.50 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 18 Day 1 | -2.86 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 16 Day 1 | -2.22 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 8 Day 1 | -1.09 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 5 Day 1 | -1.51 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 14 Day 1 | -1.73 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 2 Day 1 | -1.52 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 10 Day 1 | -2.97 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 18 Day 1 | -1.11 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 3 Day 1 | -0.46 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 6 Day 1 | -0.42 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | End of treatment | 0.74 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 4 Day 1 | -1.19 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 12 Day 1 | -1.94 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 5 Day 1 | -1.25 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 3 Day 1 | -1.24 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 6 Day 1 | -0.29 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 2 Day 1 | -2.43 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 8 Day 1 | 0.17 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 10 Day 1 | -0.19 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | End of treatment | -2.08 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 20 Day 1 | 1.88 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 24 Day 1 | 2.27 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 16 Day 1 | 0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 22 Day 1 | -2.39 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 12 Day 1 | -1.40 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 18 Day 1 | 1.88 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 14 Day 1 | -0.08 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2) | Cycle 4 Day 1 | -1.94 Units on a scale |
Secondary
Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2)
The Detection Test is a measure of psychomotor function and uses a well validated simple reaction time paradigm with playing card stimuli. In this test, the on-screen instructions ask: Has the card turned over?. A playing card is presented face down in the center of the screen. The card flips over so it is face up. As soon as the card flips over the participant must press Yes. The participant is encouraged to work as quickly as they can and be as accurate as possible. The speed and accuracy of each response are recorded and mean of the log10 transformed reaction times for correct responses is calculated. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle.
Time frame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.09 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.04 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.07 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | 0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.04 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.04 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.00 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.00 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.00 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.01 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.01 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.01 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.00 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.05 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.00 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.06 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.00 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.04 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.09 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | -0.06 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.05 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.00 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.08 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.04 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.09 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.08 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.05 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.04 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.04 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.07 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.04 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.05 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.04 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.04 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.05 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.00 Units on a scale |
Secondary
Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2)
The Identification Test is a measure of visual attention and uses a well validated choice reaction time paradigm with playing card stimuli. In this task, the playing cards are all red or black jokers. The on-screen instructions ask: Is the card red?. A playing card is presented face down in the center of the screen. The card flips over so it is face up. As soon as it flips over the participant must decide whether the card is red or not. If it is red the participant should press Yes, and if it is not red the participant should press No. The participant is encouraged to work as quickly and accurately as possible. The speed and accuracy of each response are recorded and mean of the log10 transformed reaction times for correct responses is calculated. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle.
Time frame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | 0.08 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.04 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.09 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.07 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.05 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.04 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.04 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.04 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.04 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.00 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.05 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.01 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.06 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.04 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.04 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.01 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.05 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.04 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | -0.06 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.04 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.07 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.10 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.07 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.03 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.04 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.09 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.05 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.05 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.05 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.06 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.19 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.05 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.06 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.06 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.08 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.01 Units on a scale |
Secondary
Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2)
The International Shopping List task is a measure of verbal learning and uses a well validated list learning paradigm administered using a computer. High frequencies, high imagery, concrete nouns (items from a shopping list) were read to the participant at the rate of one word every 2 seconds. Once all 12 words had been read, the participant was asked to recall as many of the words as quickly as possible. The words recalled by the participant were marked on the computer screen. When the participant could recall no more words, the same list was read again. The words recalled by the participant were recorded. This was then repeated a third time. Total number of correct responses on 3 consecutive trials at a single assessment was recorded. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle.
Time frame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.18 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | -8.49 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.58 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -2.72 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.19 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 4.77 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 2.87 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 4.52 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 1.91 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.26 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 1.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.84 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -5.72 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 1.30 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 1.46 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.28 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -1.13 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.26 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.81 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -1.62 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -1.44 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 2.59 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.66 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.81 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.87 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.66 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.60 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.25 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.59 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.86 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 2.27 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 1.36 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 2.17 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.14 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.28 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.50 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 1.69 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.11 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.27 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.56 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.80 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.36 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.13 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.45 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.94 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.69 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.24 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.08 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | -3.35 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -1.04 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 1.20 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.52 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.27 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.94 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.15 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 1.04 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 1.30 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.82 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.44 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -4.43 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 2.29 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 1.74 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 3.46 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.35 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 1.23 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 2.37 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.08 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.96 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 1.70 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.16 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.56 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 3.13 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.74 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.87 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.56 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 3.10 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.60 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.51 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 2.67 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 3.99 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 1.97 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.97 Units on a scale |
Secondary
Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2)
This test was performed in the same way as the International Shopping List Test, with the exception that, the delayed recall condition required the participant to recall the words from the list 15 30 minutes later without having the list read again. During the recognition condition, the qualified personnel read a shopping list item that may or may not have been on the original list and the participant had to respond either affirmatively (if the item was on the original list) or negatively (if it was not). Total number of correct responses made in remembering the word list after a delay was recorded. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle.
Time frame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.56 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.44 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.38 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.90 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -3.22 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.89 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -1.22 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.48 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.10 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.33 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.29 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.35 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.87 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | -2.43 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 1.06 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -1.32 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.57 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.38 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.68 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.80 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.52 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.06 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.16 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.68 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | End of treatment | -2.31 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.84 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.13 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.91 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.24 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.14 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.52 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.38 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.12 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.22 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.12 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.24 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 1.06 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.80 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.68 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.54 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.59 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.46 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.49 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.23 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.18 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | -0.80 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.77 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.25 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.22 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.19 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.11 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.12 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.24 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.64 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.85 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -1.08 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.60 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.39 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.22 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -1.80 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.09 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.40 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.25 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.30 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.19 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.87 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.28 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.30 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.16 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.37 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.35 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.22 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.42 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.00 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | -0.25 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.11 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.33 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.70 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.17 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -1.06 Units on a scale |
Secondary
Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2)
The One Back Test is a measure of working memory and uses a well validated n back paradigm with playing cards. In this task, the on-screen instructions ask: Is the previous card the same?. A playing card is presented in the center of the screen. The participant must decide whether the card is the same as the previous card. If it is the same the participant should press Yes, and if not press No. The participant is encouraged to work as quickly and accurately as possible. The speed and accuracy of each response are recorded, mean of the log10 transformed reaction times for correct responses is used to demonstrate speed of performance, and the arcsine transformation of the square root of the proportion of correct responses is used to demonstrate accuracy. Lower values of least square mean change from baseline indicate performance decline. Upper limit of 95% confidence interval of -0.00 or lower indicate statistically significant decline of performance over baseline at that cycle.
Time frame: Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment. Here, 'Number Analyzed' signifies participants evaluable for specified row.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.06 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.01 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.02 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.05 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.06 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.03 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.04 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.00 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | 0.09 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.07 Units on a scale |
| 10 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.05 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.05 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.07 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.02 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.03 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.01 Units on a scale |
| 25 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.06 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.01 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.03 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.05 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.02 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.04 Units on a scale |
| 50 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.03 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | -0.00 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 24 Day 1 | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.02 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | -0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | 0.01 Units on a scale |
| 75 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | -0.07 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | -0.00 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | -0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | End of treatment | -0.03 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | -0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | -0.18 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | -0.00 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | -0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.02 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.01 Units on a scale |
| 100 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 2 Day 1 | 0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 10 Day 1 | 0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 12 Day 1 | 0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 14 Day 1 | 0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 8 Day 1 | 0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | End of treatment | 0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 16 Day 1 | 0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 18 Day 1 | 0.05 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 5 Day 1 | 0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 20 Day 1 | 0.02 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 4 Day 1 | -0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 22 Day 1 | 0.03 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 6 Day 1 | 0.01 Units on a scale |
| 150 mg QD (Phase 1) | Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2) | Cycle 3 Day 1 | -0.00 Units on a scale |
Secondary
Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy)
Duration of response(DOR): time from first documentation of objective tumor response (CR/PR) to first documentation of PD or to death due to any cause, whichever occurred first. DOR: calculated for subgroup of participants with confirmed objective tumor response. Intracranial DOR: calculated for participants with confirmed intracranial objective response. CR:disappearance of all non-lymph node target lesions (where all target lesions are recorded with length of 0mm on Target Lesion eCRF). Any pathological lymph node (recorded as target lesion) must have reduction in short axis to \<10mm. PR:30% or more decrease in SLD of target lesion, taking as reference baseline SLD. PD:20% or more increase in the SLD of target lesions relative to baseline or smallest SLD (nadir) recorded since first dose. In addition, also demonstrate absolute increase of at least 5mm (\>=5mm) relative to baseline or smallest SLD (nadir) recorded since first dose.
Time frame: From first dose of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: DOR analysis set included all ITT participants who had confirmed objective response; intracranial DOR analysis set included all ITT participants who had CNS metastases and achieved confirmed intracranial objective response. Here, Number Analyzed signifies participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 17.16 Months |
| 10 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | NA Months |
| 25 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 16.56 Months |
| 25 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | NA Months |
| 50 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 11.10 Months |
| 50 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | 37.12 Months |
| 75 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 15.08 Months |
| 75 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | 14.52 Months |
| 100 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 7.03 Months |
| 100 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | 10.32 Months |
| 150 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 19.61 Months |
| 150 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | 17.62 Months |
| 200 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | DOR | 5.19 Months |
| 200 mg QD (Phase 1) | Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy) | Intra-cranial DOR | NA Months |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)
Cmax of midazolam was observed directly from data. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflected the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflected the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1) | Cycle 1 Day 15 | 9.697 ng/mL | Geometric Coefficient of Variation 40 |
| 10 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1) | Day -7 | 16.06 ng/mL | Geometric Coefficient of Variation 42 |
| 25 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1) | Day -7 | 11.56 ng/mL | Geometric Coefficient of Variation 48 |
| 25 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1) | Cycle 1 Day 15 | 5.734 ng/mL | Geometric Coefficient of Variation 43 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 was observed directly from data.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 67.29 ng/mL | Geometric Coefficient of Variation 18 |
| 25 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 138.1 ng/mL | Geometric Coefficient of Variation 35 |
| 50 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 359.7 ng/mL | Geometric Coefficient of Variation 27 |
| 75 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 429.6 ng/mL | Geometric Coefficient of Variation 48 |
| 100 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 550.2 ng/mL | Geometric Coefficient of Variation 32 |
| 150 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 541.0 ng/mL | Geometric Coefficient of Variation 42 |
| 200 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA ng/mL | — |
| 35 mg BID (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA ng/mL | — |
| 75 mg BID (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 550.0 ng/mL | Geometric Coefficient of Variation 23 |
| 100 mg BID (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 600.5 ng/mL | Geometric Coefficient of Variation 27 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)
Maximum observed plasma concentration (Cmax) of PF-06463922 was observed directly from data.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 50.80 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| 25 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 149.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
| 50 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | NA Nanograms per milliliter (ng/mL) | — |
| 75 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 489.1 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| 100 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 595.5 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| 150 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 760.0 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| 200 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1201 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| 35 mg BID (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 202.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57 |
| 75 mg BID (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 594.9 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| 100 mg BID (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 507.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2)
Maximum observed plasma concentration (Cmax) of PF-06463922 was observed directly from data.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number Analyzed signifies participants analyzed for this outcome measure. Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2) | Day -7 | 695.2 ng/mL | Geometric Coefficient of Variation 40 |
| 10 mg QD (Phase 1) | Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2) | Cycle 1 Day 15 | 576.5 ng/mL | Geometric Coefficient of Variation 42 |
Secondary
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)
European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ)-C30 (version 3.0) consists of 30 questions assessing 5 functional domains (physical, role, emotional, cognitive and social), global quality of life (QoL), disease/treatment related symptoms (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea), and the perceived financial impact of disease. Each scale was transformed to a range of 0 to 100 using standard EORTC algorithm. For global QoL and functional scales, higher score indicate better performance, and improvement was defined as an increase of at least 10 points, worsening was defined as a decrease of at least 10 points. For symptom scales, higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable.
Time frame: From start of study treatment until end of treatment (maximum of 8 years approximately)
Population: Patient reported outcome (PRO) evaluable analysis set included all enrolled participants who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline PRO assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in social functioning | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in global QoL | 19 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in global QoL | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in global QoL | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in physical functioning | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in physical functioning | 29 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in physical functioning | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in role functioning | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in role functioning | 15 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in role functioning | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in emotional functioning | 15 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in emotional functioning | 21 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in emotional functioning | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in cognitive functioning | 8 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in cognitive functioning | 21 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in cognitive functioning | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in social functioning | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in social functioning | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in fatigue | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in fatigue | 19 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in fatigue | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in nausea and vomiting | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in nausea and vomiting | 32 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | worsened in nausea and vomiting | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in pain | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in pain | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in pain | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in dyspnea | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in dyspnea | 19 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in dyspnea | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in insomnia | 19 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in insomnia | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in insomnia | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in appetite loss | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in appetite loss | 27 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in appetite loss | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in constipation | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in constipation | 28 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in constipation | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in diarrhea | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in diarrhea | 28 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in diarrhea | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Improved in financial difficulties | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Stable in financial difficulties | 20 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1) | Worsened in financial difficulties | 16 Participants |
Secondary
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study)
European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ)-C30 (version 3.0) consists of 30 questions assessing 5 functional domains (physical, role, emotional, cognitive and social), global quality of life (QoL), disease/treatment related symptoms (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation and diarrhea), and the perceived financial impact of disease. Each scale was transformed to a range of 0 to 100 using standard EORTC algorithm. For global QoL and functional scales, higher score indicate better performance, and improvement was defined as an increase of at least 10 points, worsening was defined as a decrease of at least 10 points. For symptom scales, higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable.
Time frame: From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: Patient reported outcome (PRO) evaluable analysis set included all enrolled participants who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline PRO assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 18 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 13 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 12 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 18 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 8 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 8 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 12 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 20 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 22 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 9 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 16 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 14 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 4 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 12 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 14 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 13 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 19 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 8 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 14 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 21 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 10 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 8 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 6 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 14 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 19 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 10 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 22 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 21 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 11 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 12 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 17 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 4 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 11 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 8 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 14 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 16 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 7 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 7 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 18 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 5 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 13 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 6 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 24 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 18 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 33 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 13 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 18 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 8 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 16 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 28 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 9 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 25 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 33 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 9 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 33 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 13 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 25 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 36 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 11 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 32 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 5 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 20 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 34 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 36 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 38 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 40 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 14 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 12 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 33 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 7 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 22 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 13 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 44 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 15 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 24 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 11 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 28 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 23 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 16 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 33 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 11 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 39 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 11 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 13 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 38 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 9 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 25 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 22 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 13 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 24 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 12 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 25 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 18 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 17 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 20 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 34 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 6 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 12 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 34 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 14 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 20 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 29 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 23 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 9 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 16 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 39 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 23 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 28 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 9 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 22 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 15 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 30 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 22 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 8 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 29 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 26 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 10 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 27 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 16 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 13 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 13 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 21 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 17 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 18 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 22 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 28 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 19 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 11 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 10 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 10 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 11 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 19 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 22 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 11 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 19 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 16 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 29 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 12 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 25 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 14 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 21 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 26 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 18 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 8 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 12 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 17 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 11 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 11 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 10 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 8 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 20 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 21 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 12 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 20 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 8 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 17 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 17 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 13 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 18 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 9 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 23 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 11 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 16 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 20 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 4 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 15 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 19 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 10 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 28 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 20 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 4 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 26 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 21 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 10 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 19 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 12 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 7 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 4 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 28 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 8 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 17 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 9 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 5 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 22 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 13 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 14 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 18 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 22 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 16 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 12 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 5 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 20 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in diarrhea | 6 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in role functioning | 15 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for insomnia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in global QoL | 18 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in role functioning | 7 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 15 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for constipation | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in social functioning | 13 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in fatigue | 6 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in global QoL | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in cognitive functioning | 11 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 8 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in fatigue | 9 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in constipation | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for emotional functioning | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for global QoL | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in fatigue | 17 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in appetite loss | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for dyspnea | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in physical functioning | 5 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in constipation | 12 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for role functioning | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in appetite loss | 20 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for social functioning | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in insomnia | 12 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in physical functioning | 23 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in constipation | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in cognitive functioning | 12 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in role functioning | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in social functioning | 6 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for nausea and vomiting | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for cognitive functioning | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in appetite loss | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in financial difficulties | 9 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in insomnia | 15 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in financial difficulties | 16 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in physical functioning | 4 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in pain | 14 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in emotional functioning | 20 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in nausea and vomiting | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for diarrhea | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in insomnia | 5 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in financial difficulties | 7 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for appetite loss | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in pain | 13 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in social functioning | 13 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in nausea and vomiting | 24 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in diarrhea | 5 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for financial difficulties | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in nausea and vomiting | 6 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in cognitive functioning | 9 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in pain | 5 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Worsened in emotional functioning | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for pain | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Stable in diarrhea | 21 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in global QoL | 12 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for physical functioning | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in emotional functioning | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Missing for fatigue | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 9 Participants |
Secondary
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable.
Time frame: From start of study treatment until end of treatment (maximum of 8 years approximately)
Population: PRO evaluable analysis set included all enrolled participants who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline PRO assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in dyspnea | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in dyspnea | 23 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in dyspnea | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in coughing | 23 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in coughing | 12 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in coughing | 8 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in hemoptysis | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in hemoptysis | 42 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in hemoptysis | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in sore mouth | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in sore mouth | 40 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in sore mouth | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in dysphagia | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in dysphagia | 37 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in dysphagia | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in peripheral neuropathy | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in peripheral neuropathy | 21 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in peripheral neuropathy | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in alopecia | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in alopecia | 29 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in alopecia | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in chest pain | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in chest pain | 22 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in chest pain | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in arm or shoulder pain | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in arm or shoulder pain | 27 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in arm or shoulder pain | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Improved in pain in other parts | 20 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Stable in pain in other parts | 12 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1) | Worsened in pain in other parts | 11 Participants |
Secondary
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study)
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable.
Time frame: From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: Patient reported outcome (PRO) evaluable analysis set included all enrolled participants who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline PRO assessment. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 14 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 17 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 18 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 9 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 15 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 18 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 5 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 25 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 24 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 11 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 16 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 10 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 23 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 7 Participants |
| 10 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 9 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 13 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 17 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 22 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 19 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 20 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 6 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 15 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 8 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 4 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 5 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 18 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 9 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 24 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 13 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 7 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 4 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 25 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 10 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 47 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 7 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 17 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 27 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 44 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 9 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 6 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 26 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 41 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 14 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 7 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 4 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 12 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 6 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 7 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 30 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 9 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 13 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 23 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 22 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 11 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 15 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 36 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 19 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 46 Participants |
| 50 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 35 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 33 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 6 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 20 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 24 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 41 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 22 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 16 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 33 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 52 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 28 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 21 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 25 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 14 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 9 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 48 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 14 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 9 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 36 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 40 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 18 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 26 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 7 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 12 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 7 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 4 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 25 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 12 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 21 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 15 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 17 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 21 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 18 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 15 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 34 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 33 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 33 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 22 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 14 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 10 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 24 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 8 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 14 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 7 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 22 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 18 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 9 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 12 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 24 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 14 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 27 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 5 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 9 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 18 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 4 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 5 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 23 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 18 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 30 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 14 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 17 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 5 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 12 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 28 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 17 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 36 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 8 Participants |
| 150 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in sore mouth | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in coughing | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-sore mouth | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in hemoptysis | 31 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in hemoptysis | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in coughing | 15 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in coughing | 16 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dyspnea | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dyspnea | 8 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dyspnea | 18 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-alopecia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dyspnea | 6 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-coughing | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in dysphagia | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in peripheral neuropathy | 9 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-Pain in other parts | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in pain in other parts | 12 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in peripheral neuropathy | 16 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in pain in other parts | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in hemoptysis | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in peripheral neuropathy | 7 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in pain in other parts | 9 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-peripheral neuropathy | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing- arm or shoulder pain | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in arm or shoulder pain | 4 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in alopecia | 4 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in arm or shoulder pain | 9 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in chest pain | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in alopecia | 21 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-dysphagia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in chest pain | 13 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in alopecia | 7 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Worsened in dysphagia | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in dysphagia | 27 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-chest pain | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in arm or shoulder pain | 19 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Improved in sore mouth | 4 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in chest pain | 17 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Stable in sore mouth | 26 Participants |
| 200 mg QD (Phase 1) | Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study) | Missing-hemoptysis | 0 Participants |
Secondary
Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy)
PR Interval was determined by ECG measurement. PR interval had following categories: change from baseline\>=25 percent, 40 to \<60 milliseconds (msec), 60 to \<80 msec and \>=80 msec. Baseline was defined as the average of the triplicate measurements prior to the first dose of study drug.
Time frame: From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: Safety analysis set: all enrolled participants who received at least 1 dose of PF-06463922. Here, Overall Number of Participants Analyzed: participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 4 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 8 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 7 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 10 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Change from baseline: >25% | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: >=80 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 60-<80 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy) | Absolute value: 40-<60 msec | 2 Participants |
Secondary
Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
Triplicate 12-lead electrocardiograms (ECGs) were performed approximately 2 minutes apart to determine mean QTc interval (QT interval corrected for heart rate). QT interval was corrected for heart rate using Fridericia's formula to provide QTcF. Absolute values and changes from baseline were summarized according to pre-defined criteria. Baseline was defined as the last evaluation on or prior to the first dose of study treatment.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of PF-06463922.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 2 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 10 Participants |
| EXP-1 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 5 Participants |
| EXP-2 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 8 Participants |
| EXP-2 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 8 Participants |
| EXP-2 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| EXP-3 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 11 Participants |
| EXP-3 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 18 Participants |
| EXP-3 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 1 Participants |
| EXP-3 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 3 Participants |
| EXP-3 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 9 Participants |
| EXP-4 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 0 Participants |
| EXP-4 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 20 Participants |
| EXP-4 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 1 Participants |
| EXP-5 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| EXP-5 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 13 Participants |
| EXP-5 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 1 Participants |
| EXP-5 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 7 Participants |
| EXP-5 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 3 Participants |
| EXP-6 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 12 Participants |
| EXP-6 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 1 Participants |
| EXP-6 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 9 Participants |
| EXP-6 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| EXP-6 (Phase 2) | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 0 Participants |
| DDI Sub-study | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 480 to <500 msec | 1 Participants |
| DDI Sub-study | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF Increase: 30 to <60 msec | 7 Participants |
| DDI Sub-study | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=60 msec | 1 Participants |
| DDI Sub-study | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: 450 to <480 msec | 7 Participants |
| DDI Sub-study | Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | QTcF: >=500 msec | 1 Participants |
Secondary
Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 1)
Plasma circulating nucleic acid (CNA) samples were analyzed for ALK kinase domain mutations by digital polymerase chain reaction (PCR) BEAMing technology. Number of participants with one or more ALK mutations is presented.
Time frame: Screening (up to 28 days)
Population: CNA peripheral blood analysis set included all participants of the ITT analysis set who had at least 1 molecular biomarker assayed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 1) | 14 Participants |
Secondary
Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2)
Plasma CNA samples were analyzed for ALK kinase domain mutations by Next Generation Sequencing (NGS). Number of participants with one or more ALK mutations is presented.
Time frame: Screening (up to 28 days)
Population: CNA peripheral blood analysis set included all participants of the ITT analysis set who had at least 1 molecular biomarker assayed. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2) | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2) | 6 Participants |
| 50 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2) | 8 Participants |
| 75 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2) | 17 Participants |
| 100 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2) | 14 Participants |
Secondary
Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 1)
Tumor tissues from archived tissue specimens and/or a de novo biopsy were analyzed for ALK kinase domain mutations. Number of participants with one or more ALK mutations is presented.
Time frame: Screening (up to 28 days)
Population: Tumor Tissue analysis set included all participants of the ITT analysis set who had at least 1 molecular tumor biomarker assayed from either the screening archival or screening de novo tumor biopsy sample (or both).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 1) | 7 Participants |
Secondary
Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2)
Tumor tissues from archived tissue specimens and/or a de novo biopsy were analyzed for ALK kinase domain mutations. Number of participants with one or more ALK mutations is presented.
Time frame: Screening (up to 28 days)
Population: Tumor Tissue analysis set included all participants of the ITT analysis set who had at least 1 molecular tumor biomarker assayed from either the screening archival or screening de novo tumor biopsy sample (or both).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2) | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2) | 7 Participants |
| 50 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2) | 8 Participants |
| 75 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2) | 12 Participants |
| 100 mg QD (Phase 1) | Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2) | 13 Participants |
Secondary
Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1)
Duration of response(DOR): time from first documentation of objective tumor response (CR/PR) to first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. DOR: calculated for subgroup of participants with confirmed objective tumor response. Intracranial DOR: calculated for participants with confirmed intracranial objective response. CR:disappearance of all non-lymph node target lesions (where all target lesions are recorded with length of 0mm on Target Lesion eCRF). Any pathological lymph node (recorded as target lesion) must have reduction in short axis to \<10mm. PR:30% or more decrease in SLD of target lesion, taking as reference baseline SLD. PD:20% or more increase in the SLD of target lesions relative to baseline or smallest SLD (nadir) recorded since first dose. In addition, also demonstrate absolute increase of at least 5mm (\>=5mm) relative to baseline or smallest SLD (nadir) recorded since first dose.
Time frame: From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Population: DOR analysis set included all ITT participants who had confirmed objective response; intracranial DOR analysis set included all ITT participants who had CNS metastases and achieved confirmed intracranial objective response. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data foe every row. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | <3 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 15 Months to <18 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 3 Months to <6 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 3 Months to <6 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 6 Months to <9 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 9 Months to <12 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 9 Months to <12 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 6 Months to <9 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 12 Months to <15 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 18 Months to <21 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 15 Months to <18 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 9 Months to <12 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 18 Months to <21 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 6 Months to <9 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 21 Months to <24 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 12 Months to <15 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | >=24 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 21 Months to <24 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | <3 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 15 Months to <18 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 3 Months to <6 Months | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 12 Months to <15 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 6 Months to <9 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 18 Months to <21 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 9 Months to <12 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | >=24 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 12 Months to <15 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 21 Months to <24 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 15 Months to <18 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 3 Months to <6 Months | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 18 Months to <21 Months | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | >=24 Months | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 21 Months to <24 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | <3 Months | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | >=24 Months | 6 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | <3 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | >=24 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | <3 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 3 Months to <6 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 6 Months to <9 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 9 Months to <12 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 12 Months to <15 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 15 Months to <18 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 18 Months to <21 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | 21 Months to <24 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with DOR | >=24 Months | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | <3 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 3 Months to <6 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 6 Months to <9 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 9 Months to <12 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 12 Months to <15 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 15 Months to <18 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 18 Months to <21 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | 21 Months to <24 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored-DOR | >=24 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | <3 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 3 Months to <6 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 6 Months to <9 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 9 Months to <12 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 12 Months to <15 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 15 Months to <18 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 18 Months to <21 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | 21 Months to <24 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants with intracranial DOR | >=24 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | <3 Months | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 3 Months to <6 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 6 Months to <9 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 9 Months to <12 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 12 Months to <15 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 15 Months to <18 Months | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 18 Months to <21 Months | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1) | Participants censored- intracranial DOR | 21 Months to <24 Months | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry
Chemistry evaluation included alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), blood bilirubin, creatine phosphokinase (CPK), creatinine, gamma-glutamyl transferase (GGT), calcium, sodium, potassium, magnesium, albumin, glucose (non-fasted), albumin, phosphorus or phosphate, serum amylase and lipase.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: Safety analysis set: all enrolled participants who received at least 1 dose of PF-06463922. Overall Number of Participants Analyzed: participants evaluable for this outcome measure. 'Number Analyzed': participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 7 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 6 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 8 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 6 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 4 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 9 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 4 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 8 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 4 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 8 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 4 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 7 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 13 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 10 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 2 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 3 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 6 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 10 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 8 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 11 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 8 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 10 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 13 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 17 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 16 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 11 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 28 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 3 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 19 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 5 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 6 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 7 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 13 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 20 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 3 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 9 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 9 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 13 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 4 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 9 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 22 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 1 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 13 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 4 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 15 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 15 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 6 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 6 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 7 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 18 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 5 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 10 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 3 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 21 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 23 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 14 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 10 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 23 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 2 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 15 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 29 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 18 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 37 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 9 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 7 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 36 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 16 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 40 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 2 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 25 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 37 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 3 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 33 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 48 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 20 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 13 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 27 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 48 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 2 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 16 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 5 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 19 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 23 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 43 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 20 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 12 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 9 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 9 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 25 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 8 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 12 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 34 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 11 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 32 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 7 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 8 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 4 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 16 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 4 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 34 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 15 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 6 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 1 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 21 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 2 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 16 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 25 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 8 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 6 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 18 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 12 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 5 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 4 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 15 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 3 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 6 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 14 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 31 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 15 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 15 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 2 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 18 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 14 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 1 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 37 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 15 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 29 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 2 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 12 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Lipase increased | 7 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | GGT increased | 0 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypocalcemia | 6 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoalbuminemia | 18 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | ALT increased | 10 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypermagnesemia | 0 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Alkaline phosphatase increased | 9 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypophosphatemia | 9 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Creatinine increased | 20 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypernatremia | 3 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Blood bilirubin increased | 1 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperglycemia | 23 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | AST increased | 11 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypomagnesemia | 15 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Serum amylase increased | 4 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypercalcemia | 5 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | CPK increased | 1 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypokalemia | 7 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyperkalemia | 5 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hypoglycemia | 6 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry | Hyponatremia | 10 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis
Coagulation evaluation included activated partial thromboplastin time, international normalized ratio (INR), and prothrombin time. Lipid evaluation included Cholesterol and triglycerides.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: Safety analysis set: all enrolled participants who received at least 1 dose of PF-06463922. Overall Number of Participants Analyzed: participants evaluable for this outcome measure. 'Number Analyzed': participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 11 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 16 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 16 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 3 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 30 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 30 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 3 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 26 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 26 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 1 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 56 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 3 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 58 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 3 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 6 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 61 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 6 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 64 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 6 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 3 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 45 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 3 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 2 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 45 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 4 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 6 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 7 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 43 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 44 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Prothrombin time | 6 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Activated partial thromboplastin time prolonged | 2 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Hypertriglyceridemia | 31 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | INR increased | 3 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis | Cholesterol high | 31 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology
Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. Hematology parameters with any abnormalities were reported in this outcome measure.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of PF-06463922. Here 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 7 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 10 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 4 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 4 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 16 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 3 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 4 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 8 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 7 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 9 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 24 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 12 Participants |
| EXP-1 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 4 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 22 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 10 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 14 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 3 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 3 Participants |
| EXP-2 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 5 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 6 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 18 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 8 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 9 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 1 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 51 Participants |
| EXP-3 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 30 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 3 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 52 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 12 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 13 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 10 Participants |
| EXP-4 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 31 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 1 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 21 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 2 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 13 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 35 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 2 Participants |
| EXP-5 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 8 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 26 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 7 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 0 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 10 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 13 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 1 Participants |
| EXP-6 (Phase 2) | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 34 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Anemia | 25 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count increased | 2 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Hemoglobin increased | 1 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Lymphocyte count decreased | 15 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | White blood cell decreased | 4 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Neutrophil count decreased | 3 Participants |
| DDI Sub-study | Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology | Platelet count decreased | 8 Participants |
Secondary
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study)
Left Ventricular Ejection Fraction (LVEF) was determined by echocardiogram. Baseline was defined as the measurement prior to the first dose of study treatment.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of PF-06463922.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 5 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 4 Participants |
| EXP-2 (Phase 2) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 2 Participants |
| EXP-3 (Phase 2) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 13 Participants |
| EXP-4 (Phase 2) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 14 Participants |
| EXP-5 (Phase 2) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 3 Participants |
| EXP-6 (Phase 2) | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 5 Participants |
| DDI Sub-study | Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study) | 2 Participants |
Secondary
Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2)
The Columbia Suicide Severity Rating Scale (C-SSRS) was used to analyze participants' suicidal ideation and behavior, and it is a unique, simple and short method of assessing both behavior and ideation that tracks all suicidal events and provides a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation and deterrents), all of which are significantly predictive of completed suicide. Maximum score of 4 or 5 indicates maximum suicidal ideation and minimum score of 0 indicates no suicidal ideation.
Time frame: From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2)
Population: PRO evaluable analysis set included all enrolled participants who received study treatment, had a baseline test assessment and at least 1 on-study test assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal behavior | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal ideation | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal behavior | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal ideation | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal ideation | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal behavior | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal ideation | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal behavior | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal behavior | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal ideation | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal ideation | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2) | Suicidal behavior | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study)
AE: any untoward medical occurrence in clinical investigation participant administered a product or medical device, regardless of causal relationship to study treatment. Treatment-emergent AEs (TEAEs): AEs which occurred for first time during effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs): any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of ability to conduction normal life function). AEs included SAEs and non-serious AEs. Severity was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.Grade1: mild, Grade2: moderate, Grade3: severe, Grade4: Life threatening consequences; urgent intervention indicated, Grade 5: death related to AE.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: The safety analysis set included all enrolled participants who received at least 1 dose of PF-06463922.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 3 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 2 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 12 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 11 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 6 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 6 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 6 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 17 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 16 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 1 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 12 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 10 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 4 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 2 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 2 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 3 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 3 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 2 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 3 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 4 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 4 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 4 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 3 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 30 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 30 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 15 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 3 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 22 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 13 Participants |
| EXP-1 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 3 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 27 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 27 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 11 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 22 Participants |
| EXP-2 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 15 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 10 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 31 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 56 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 59 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 8 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 43 Participants |
| EXP-3 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 34 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 11 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 50 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 31 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 31 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 65 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 6 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 61 Participants |
| EXP-4 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 23 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 46 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 36 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 22 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 43 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 6 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 9 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 45 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 25 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 7 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 4 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 21 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 36 Participants |
| EXP-6 (Phase 2) | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 47 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (treatment-related) | 16 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (treatment-related) | 0 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (all causality) | 13 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (all causality) | 32 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | SAEs (treatment-related) | 1 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | AEs (treatment-related) | 31 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 5 (all causality) | 5 Participants |
| DDI Sub-study | Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study) | Grade 3 or 4 (all causality) | 24 Participants |
Secondary
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position. Body weight was also measured.
Time frame: From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: Safety analysis set: all enrolled participants who received at least 1 dose of PF-06463922. Overall Number of Participants Analyzed: participants evaluable for this outcome measure. 'Number Analyzed': participants evaluable for specified row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 2 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 1 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 10 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 2 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 1 Participants |
| 25 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 1 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 50 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 3 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 1 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 5 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 2 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 8 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 75 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 7 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 5 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 7 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 2 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 3 Participants |
| 100 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 6 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 3 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 2 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 1 Participants |
| 150 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 1 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 2 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 200 mg QD (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 1 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 0 Participants |
| 35 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 1 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 75 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 2 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 1 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 0 Participants |
| 100 mg BID (Phase 1) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 1 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 12 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 9 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 11 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 11 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 9 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 2 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 9 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| EXP-1 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 1 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 5 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 1 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 14 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 3 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 7 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 12 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 1 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 2 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| EXP-2 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 7 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 17 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 1 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 8 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 5 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 3 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 10 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 5 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 14 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 5 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 15 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 10 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 21 Participants |
| EXP-3 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 19 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 10 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 2 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 2 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 7 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 15 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 10 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 1 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 9 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 15 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 16 Participants |
| EXP-4 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 4 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 2 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 10 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 9 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 5 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 15 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 3 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 2 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 11 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 17 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 4 Participants |
| EXP-5 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 4 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 2 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 2 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 14 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 1 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 9 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 2 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 12 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 2 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 9 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 3 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 17 Participants |
| EXP-6 (Phase 2) | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 5 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=20 mmHg | 8 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=60 mmHg | 0 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in weight >=10% | 1 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: 10% to <20% | 9 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting DBP >=40 mmHg | 0 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=40 mmHg | 1 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting pulse rate >=30 bpm | 8 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate <50 bpm | 2 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=20 mmHg | 7 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting SBP >=60 mmHg | 0 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting SBP >=40 mmHg | 4 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Decrease in sitting pulse rate >=30 bpm | 4 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in sitting DBP >=40 mmHg | 0 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Sitting pulse rate >120 bpm | 3 Participants |
| DDI Sub-study | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study) | Increase in weight: >=20% | 3 Participants |
Secondary
Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Rac was calculated as Day 15 AUCtau/Day -7 AUCtau or Day 1 AUCtau, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (12 and 24 hours for BID and QD dosing regimen, respectively).
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.543 Ratio | Standard Deviation 0.075056 |
| 25 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.237 Ratio | Standard Deviation 0.20817 |
| 50 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.105 Ratio | — |
| 75 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.121 Ratio | Standard Deviation 0.44575 |
| 100 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.071 Ratio | Standard Deviation 0.31138 |
| 150 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.000 Ratio | Standard Deviation 0.79137 |
| 200 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.6500 Ratio | — |
| 35 mg BID (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA Ratio | — |
| 75 mg BID (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.231 Ratio | Standard Deviation 0.35228 |
| 100 mg BID (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.523 Ratio | Standard Deviation 0.29569 |
Secondary
Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2)
Rac was calculated as Day 15 AUCtau/Day -7 AUCtau, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen which was adopted in Phase 2).
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2) | 1.082 Ratio | Standard Deviation 0.42701 |
Secondary
Overall Survival (OS) (Phase 1)
OS was defined as the time from first dose to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.
Time frame: 3 years
Population: The intent-to-treat (ITT) analysis set included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922. Here, Number Analyzed signifies participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mg QD (Phase 1) | Overall Survival (OS) (Phase 1) | 22.3 Months |
| 25 mg QD (Phase 1) | Overall Survival (OS) (Phase 1) | NA Months |
Secondary
Overall Survival (Phase 2 and DDI Substudy)
OS was defined as the time from first dose to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.
Time frame: From first dose of study treatment until date of death (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: ITT analysis set included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | NA Months |
| 25 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | 52.5 Months |
| 50 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | NA Months |
| 75 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | 18.7 Months |
| 100 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | 20.4 Months |
| 150 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | 49.7 Months |
| 200 mg QD (Phase 1) | Overall Survival (Phase 2 and DDI Substudy) | 19.8 Months |
Secondary
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1)
Tumor response was evaluated according to RECIST version 1.1, and disease control: confirmed CR, confirmed PR, or stable disease (SD). Intracranial assessment was only performed for participants CNS metastases. CR was defined as disappearance of all non-lymph node target lesions (where all target lesions are recorded with length of 0mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as 30% or more decrease in SLD of target lesions, taking as reference baseline SLD. Progressive disease: 20% or more increase in SLD of target lesions relative to baseline or smallest SLD (nadir) recorded since first dose. In addition to relative increase of 20%, SLD must also demonstrate absolute increase of at least 5mm (\>=5mm) relative to baseline or smallest SLD (nadir) recorded since first dose. Results presented here were based on independent central review.
Time frame: 12 and 24 weeks
Population: The intent-to-treat (ITT) analysis set was used for overall response assessment, and included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; participants with CNS metastases in the ITT analysis set was used for intracranial response assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | DCR at Week 12 | 53.7 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | DCR at Week 24 | 39.0 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | Intracranial DCR at Week 12 | 50.0 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | Intracranial DCR at Week 24 | 41.2 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | Intracranial DCR at Week 24 | 37.5 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | DCR at Week 12 | 58.3 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | Intracranial DCR at Week 12 | 37.5 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1) | DCR at Week 24 | 50.0 Percentage of participants |
Secondary
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy)
Tumor response was evaluated according to RECIST version 1.1, and disease control was defined as confirmed CR, confirmed PR, or stable disease (SD). CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. SD= when neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD is observed, taking as reference the smallest sum diameters while on study. Intracranial assessment was only performed for participants CNS metastases. Results presented here were based on independent central review.
Time frame: Weeks 12 and 24
Population: The intent-to-treat (ITT) analysis set was used for overall response assessment, and included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; participants with CNS metastases in the ITT analysis set was used for intracranial response assessment. Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 87.5 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 75.0 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 93.3 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 83.3 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 85.2 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 94.1 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 70.6 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 63.0 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 68.3 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 75.8 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 51.7 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 60.6 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 75.6 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 49.2 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 64.6 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 62.2 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 48.6 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 32.6 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 67.6 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 50.0 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 66.0 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 48.9 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 52.0 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 72.0 Percentage of participants |
| 200 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 24 | 34.4 Percentage of participants |
| 200 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Disease control rate at Week 12 | 56.3 Percentage of participants |
| 200 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 24 | 43.8 Percentage of participants |
| 200 mg QD (Phase 1) | Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy) | Intra-cranial disease control rate at Week 12 | 56.3 Percentage of participants |
Secondary
Percentage of Participants With Overall and Intracranial Objective Response (Phase 1)
Objective response (OR) refers to confirmed CR or PR according to RECIST version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review.
Time frame: From start of study treatment until CR or PR (maximum of 8 years approximately)
Population: The ITT analysis set was used for overall response assessment and included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; participants with CNS metastases in the ITT analysis set was used for intracranial response assessment. Here, Number Analyzed signifies participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 1) | Objective response | 39.0 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 1) | Intracranial objective response | 41.2 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 1) | Objective response | 50.0 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 1) | Intracranial objective response | 50.0 Percentage of participants |
Secondary
Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)
Dosing interval was 24 hours for QD dosing regimen. Aetau% was calculated as 100\*Ae24/dose, where Ae24 was the cumulative amount of drug recovered unchanged in urine up to 24 hours post-dose.
Time frame: 0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. As planned, this parameter was only analyzed for 100 mg QD group. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1) | 0.4017 Percentage of recovered PF-06463922 | Standard Deviation 0.11074 |
Secondary
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)
The probability of the first event being a CNS progression, a non-CNS progression, or death was evaluated with a competing risk approach by estimating cumulative incidence functions (range: 0-1) relative to the analysis set. The time to first event being a Competing Event (either CNS progression or non CNS progression or Death) was defined as time from first dose until the date of that specific event. Participants not known to have any of the Competing Events were censored on the date they were last assessed for disease status for PFS. Participants who presented one type of event were counted as a competing cause of failure for the analysis of other type of events. For each type of event, the cumulative incidence function corresponding to the nearest time point preceding 1 year is presented. The results are based on independent central review.
Time frame: 3 years
Population: The intent-to-treat (ITT) analysis set included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1) | Death | 0.060 Probability of events |
| 10 mg QD (Phase 1) | Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1) | CNS progression | 0.260 Probability of events |
| 10 mg QD (Phase 1) | Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1) | Non CNS progression | 0.352 Probability of events |
Secondary
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2)
Probability of first event being CNS progression, non-CNS progression, or death was evaluated with competing risk approach by estimating cumulative incidence functions (range: 0-1) relative to analysis set. Time to first event being Competing Event (either CNS progression or non CNS progression or Death) = time from first dose until date of that specific event. Participants not known to have any of Competing Events were censored on date they were last assessed for disease status for PFS. Participants who presented one type of event were counted as competing cause of failure for analysis of other type of events. For each type of event, cumulative incidence function corresponding to nearest time point preceding 1 year is presented. PD:20% or more increase in SLD of target lesion relative to baseline or smallest SLD (nadir) recorded since first dose. SLD must demonstrate absolute increase of atleast 5mm(\>=5 mm) relative to baseline or smallest SLD (nadir) recorded since first dose.
Time frame: From first dose of study treatment until first event of CNS progression (maximum of 7.5 years for Phase 2)
Population: The ITT analysis set included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2) | CNS progression | 0.179 Probability of events |
| 10 mg QD (Phase 1) | Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2) | Non CNS progression | 0.325 Probability of events |
| 10 mg QD (Phase 1) | Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2) | Death | 0.055 Probability of events |
Secondary
Progression-Free Survival (PFS) (Phase 1)
PFS was defined as the time from the first dose of study treatment to the first documentation of objective PD or to death on study due to any cause, whichever came first. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. Results presented here were based on independent central review.
Time frame: From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Population: PFS analysis set included all participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 1) | 5.4 Months |
| 25 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 1) | 10.1 Months |
Secondary
Progression-Free Survival (PFS) (Phase 2 and DDI Substudy)
PFS was defined as the time from the first dose of study treatment to the first documentation of objective PD or to death on study due to any cause, whichever came first. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. Results presented here were based on independent central review.
Time frame: From first dose of study treatment to first documentation of objective PD or death due to any cause, whichever came first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: PFS analysis set included all participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 16.6 Months |
| 25 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 20.6 Months |
| 50 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 6.9 Months |
| 75 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 7.3 Months |
| 100 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 5.5 Months |
| 150 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 9.9 Months |
| 200 mg QD (Phase 1) | Progression-Free Survival (PFS) (Phase 2 and DDI Substudy) | 5.7 Months |
Secondary
Renal Clearance (CLr) of PF-06463922 (Phase 1)
Renal clearance was calculated as Aetau/AUCtau, where Aetau was the cumulative amount of drug recovered unchanged in urine up to dosing interval tau (24 hours for QD dosing regimen), and AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen).
Time frame: 0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. As planned, this parameter was only analyzed for 100 mg QD group. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Renal Clearance (CLr) of PF-06463922 (Phase 1) | 61.31 ml/hour | Geometric Coefficient of Variation 58 |
Secondary
Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Rss was calculated as Day 15 AUCtau/Day -7 AUCinf, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (12 and 24 hours for BID and QD dosing regimen, respectively), and AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA Ratio | — |
| 25 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.5600 Ratio | — |
| 50 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.6131 Ratio | Standard Deviation 0.29021 |
| 75 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.6603 Ratio | Standard Deviation 0.18604 |
| 100 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.3935 Ratio | — |
| 150 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA Ratio | — |
| 200 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | NA Ratio | — |
| 35 mg BID (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.7687 Ratio | Standard Deviation 0.13552 |
Secondary
Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2)
Rss was calculated as Day 15 AUCtau/Day -7 AUCinf, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen which was adopted in Phase 2), and AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2) | 0.6577 Ratio | Standard Deviation 0.28627 |
Secondary
Terminal Half-Life of Midazolam (Phase 1)
Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for midazolam included all participants who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg QD (Phase 1) | Terminal Half-Life of Midazolam (Phase 1) | Day -7 | 4.620 Hours | Standard Deviation 1.9328 |
| 10 mg QD (Phase 1) | Terminal Half-Life of Midazolam (Phase 1) | Cycle 1 Day 15 | 3.343 Hours | Standard Deviation 2.0358 |
| 25 mg QD (Phase 1) | Terminal Half-Life of Midazolam (Phase 1) | Day -7 | 5.120 Hours | — |
| 25 mg QD (Phase 1) | Terminal Half-Life of Midazolam (Phase 1) | Cycle 1 Day 15 | 5.257 Hours | Standard Deviation 5.0639 |
Secondary
Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)
Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | NA Hours (hr) | — |
| 25 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | 23.70 Hours (hr) | — |
| 50 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | 27.22 Hours (hr) | Standard Deviation 8.2961 |
| 75 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | 20.89 Hours (hr) | Standard Deviation 5.0308 |
| 100 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | 19.80 Hours (hr) | Standard Deviation 3.3045 |
| 150 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | 25.55 Hours (hr) | — |
| 200 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | NA Hours (hr) | — |
| 35 mg BID (Phase 1) | Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) | 17.18 Hours (hr) | Standard Deviation 5.1874 |
Secondary
Terminal Half-Life of PF-06463922 (Phase 2)
Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg QD (Phase 1) | Terminal Half-Life of PF-06463922 (Phase 2) | 23.58 Hours | Standard Deviation 9.3743 |
Secondary
Time for Cmax (Tmax) of Midazolam (Phase 1)
Tmax of midazolam was observed directly from data as time of first occurrence. Only participants in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for midazolam included all participants who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Time for Cmax (Tmax) of Midazolam (Phase 1) | Day -7 | 0.50 Hours |
| 10 mg QD (Phase 1) | Time for Cmax (Tmax) of Midazolam (Phase 1) | Cycle 1 Day 15 | 0.50 Hours |
| 25 mg QD (Phase 1) | Time for Cmax (Tmax) of Midazolam (Phase 1) | Day -7 | 0.50 Hours |
| 25 mg QD (Phase 1) | Time for Cmax (Tmax) of Midazolam (Phase 1) | Cycle 1 Day 15 | 0.50 Hours |
Secondary
Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Tmax of PF-06463922 was observed directly from data as time of first occurrence.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.00 Hours |
| 25 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.00 Hours |
| 50 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 2.00 Hours |
| 75 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.03 Hours |
| 100 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.13 Hours |
| 150 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.30 Hours |
| 200 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 1.61 Hours |
| 35 mg BID (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.50 Hours |
| 75 mg BID (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 0.55 Hours |
| 100 mg BID (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) | 2.00 Hours |
Secondary
Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)
Tmax of PF-06463922 was observed directly from data as time of first occurrence.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.98 Hours |
| 25 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 2.00 Hours |
| 50 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.25 Hours |
| 75 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.09 Hours |
| 100 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.96 Hours |
| 150 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.05 Hours |
| 200 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 2.00 Hours |
| 35 mg BID (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.20 Hours |
| 75 mg BID (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 1.23 Hours |
| 100 mg BID (Phase 1) | Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) | 2.00 Hours |
Secondary
Time for Cmax (Tmax) of PF-06463922 (Phase 2)
Tmax of PF-06463922 was observed directly from data as time of first occurrence.
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Population: PK parameter analysis set for PF-06463922 included all enrolled participants who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. Here, Number Analyzed signifies participants analyzed for this outcome measure. Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 (Phase 2) | Day -7 | 1.15 Hours |
| 10 mg QD (Phase 1) | Time for Cmax (Tmax) of PF-06463922 (Phase 2) | Cycle 1 Day 15 | 1.96 Hours |
Secondary
Time to Progression on the Last Prior Therapy (Phase 2)
TTP on the last prior therapy was defined as time from the first dose date of the last prior treatment regimen to the date of progression. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose.
Time frame: From first dose of study treatment to the date of progression (maximum of 7.5 years for Phase 2)
Population: ITT analysis set included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922. As planned in SAP, this outcome measure was not analyzed for EXP-1 and EXP-6 groups. Here, 'Number Analyzed' signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy before PF-06463922 | 11.5 Months |
| 10 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy other than ALK+/ROS1+ TKI | 19.6 Months |
| 10 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior ALK+/ROS1+ TKI treatment | 11.5 Months |
| 25 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy before PF-06463922 | 12.8 Months |
| 25 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy other than ALK+/ROS1+ TKI | 8.5 Months |
| 25 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior ALK+/ROS1+ TKI treatment | 13.8 Months |
| 50 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior ALK+/ROS1+ TKI treatment | 12.1 Months |
| 50 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy before PF-06463922 | 10.2 Months |
| 50 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy other than ALK+/ROS1+ TKI | 5.0 Months |
| 75 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy before PF-06463922 | 3.7 Months |
| 75 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior systemic therapy other than ALK+/ROS1+ TKI | 5.6 Months |
| 75 mg QD (Phase 1) | Time to Progression on the Last Prior Therapy (Phase 2) | Prior ALK+/ROS1+ TKI treatment | 3.7 Months |
Secondary
Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy)
Time to progression (TTP) was defined as the time from the first dose of study treatment to the first documentation of objective PD. Intracranial TTP was defined as the time from the first dose of study treatment to the date of the first documentation of objective progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases. Progressive disease was defined by a 20% or more increase in the SLD of target lesions relative to baseline or the smallest SLD (nadir) recorded since first dose. In addition to the relative increase of 20%, SLD must also demonstrate an absolute increase of at least 5 mm (\>= 5 mm) relative to baseline or the smallest SLD (nadir) recorded since the first dose. Results presented here were based on independent central review.
Time frame: From first dose of study treatment to the first documentation of objective PD (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: ITT analysis set was used for TTP determination and included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; ITT participants with CNS metastases were analyzed for intracranial TTP.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | NA Months |
| 10 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 17.7 Months |
| 25 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | NA Months |
| 25 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 20.6 Months |
| 50 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 8.2 Months |
| 50 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | NA Months |
| 75 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | 22.1 Months |
| 75 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 8.4 Months |
| 100 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | 16.4 Months |
| 100 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 5.6 Months |
| 150 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 12.5 Months |
| 150 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | NA Months |
| 200 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | Intracranial TTP | NA Months |
| 200 mg QD (Phase 1) | Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy) | TTP | 5.7 Months |
Secondary
Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)
Time to tumor response (TTR) was defined as the time from the first dose of study treatment to the first documentation of objective tumor response (CR or PR). For participants whose objective response proceeded from PR to CR, the onset of PR was taken as the onset of response. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. TTR was only calculated for the subgroup of participants with a confirmed objective tumor response. Intracranial TTR was only calculated for participants with confirmed intracranial objective response. Results presented here were based on independent central review.
Time frame: From start of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 8 years approximately)
Population: TTR analysis set included all ITT participants who had confirmed objective response; intracranial TTR analysis set included all ITT participants who had CNS metastases and achieved confirmed intracranial objective response.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 1) | TTR | 1.4 Months |
| 10 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 1) | Intracranial TTR | 1.4 Months |
| 25 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 1) | TTR | 1.4 Months |
| 25 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 1) | Intracranial TTR | 1.4 Months |
Secondary
Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study)
Time to tumor response (TTR) was defined as the time from the first dose of study treatment to the first documentation of objective tumor response (CR or PR). For participants whose objective response proceeded from PR to CR, the onset of PR was taken as the onset of response. TTR was only calculated for the subgroup of participants with a confirmed objective tumor response. Intracranial TTR was only calculated for participants with confirmed intracranial objective response. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 mm on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 % or more decrease in SLD of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review.
Time frame: From first dose of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: TTR analysis set included all ITT participants who had confirmed objective response; intracranial TTR analysis set included all ITT participants who had CNS metastases and achieved confirmed intracranial objective response. Here, Number Analyzed signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 1.4 Months |
| 10 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 2.1 Months |
| 25 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 1.4 Months |
| 25 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 1.4 Months |
| 50 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 1.4 Months |
| 50 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 1.4 Months |
| 75 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 2.6 Months |
| 75 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 1.7 Months |
| 100 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 1.4 Months |
| 100 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 1.4 Months |
| 150 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 1.4 Months |
| 150 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 1.4 Months |
| 200 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | TTR | 1.4 Months |
| 200 mg QD (Phase 1) | Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study) | Intracranial TTR | 2.0 Months |
Other Pre-specified
Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study)
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. CR was defined as the disappearance of all non-lymph node target lesions (where all target lesions are recorded with a length of 0 milliliter (mm) on Target Lesions eCRF). Any pathological lymph nodes (recorded as target lesion) must have reduction in short axis to \<10 mm. PR was defined as a 30 percent (%) or more decrease in sum of lesion dimensions (SLD) of target lesions, taking as reference the baseline SLD. Results presented here were based on independent central review.
Time frame: From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Population: ITT analysis set was used for overall response assessment and included all enrolled participants with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; participants with central nervous system (CNS) metastases in the ITT analysis set were used for intracranial response assessment. Here, Number Analyzed signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 75.0 Percentage of participants |
| 10 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 90.0 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 77.8 Percentage of participants |
| 25 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 58.8 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 66.7 Percentage of participants |
| 50 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 56.7 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 40.0 Percentage of participants |
| 75 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 53.3 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 43.2 Percentage of participants |
| 100 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 37.0 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 38.3 Percentage of participants |
| 150 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 56.0 Percentage of participants |
| 200 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Objective response | 40.6 Percentage of participants |
| 200 mg QD (Phase 1) | Percentage of Participants With Overall and Intracranial Objective Response (Phase 2 and DDI Sub-study) | Intracranial objective response | 25.0 Percentage of participants |