Cancer
Conditions
Brief summary
A phase 1 dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of PF-04691502 in adult cancer patients with solid tumors.
Interventions
DRUGPF-04691502
Once daily continuous dosing. Dose escalation to Maximally tolerated dose (MTD) until progression or discontinuation.
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
* Patients with a histologically or cytologically confirmed malignant solid tumor for which there is no currently approved treatment or which is unresponsive to currently approved therapies. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 * Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours of the first dose of PF-04961502, These patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate * Adequate Bone Marrow Function, including: 1. Absolute neutrophil count (ANC) ≥1500 cells/mm3 2. Platelets ≥75,000 cells/mm3 3. Hemoglobin ≥9 mg/dL * Adequate Renal Function, including: SrCr \<1.5 x ULN (upper limit of normal). OR Estimated creatinine clearance ≥60 mL/min, as calculated using method standard for the institution * Adequate Liver Function, including: Bilirubin ≤1.5 x ULN AST (SGOT) ≤2.5 x ULN ALT (SGPT) ≤2.5 x ULN * Adequate glucose control, including no previous diagnosis of diabetes mellitus and HbA1c \<7%. * Adequate Cardiac Function, including: 12-Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention. QTc interval ≤470 msec and no history of Torsades des Pointes or other symptomatic QTc abnormality
Exclusion criteria
* Patients with known active brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable * Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 2 weeks of Baseline disease assessments * Any surgery (not including minor procedures such as lymph node biopsy) within 4 weeks of Baseline disease assessments; or not fully recovered from any side effects of previous procedures * Prior therapy with an agent that is known or proposed to be active by action on PI3K and/or mTOR * Prior high-dose chemotherapy requiring hematopoetic stem cell transplantation within 12 months of study treatment start * Uncontrolled or significant cardiovascular disease: A myocardial infarction within 12 months Uncontrolled angina within 6 months Congestive heart failure within 6 months. Diagnosed or suspected congenital long QT syndrome. Any history of ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). Any history of second or third degree heart block (may be eligible if currently have a pacemaker) Heart rate \<50/minute on pre-entry electrocardiogram Uncontrolled hypertension. * Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors or inducers * Current use or anticipated need for food or drugs that are known potent CYP1A2 inhibitors or inducers * Concurrent administration of herbal preparations * Breast feeding: No studies have been conducted in humans to assess the impact of PF-04691502 on milk production, its presence in breast milk and its effects on the breast-fed child. Because drugs are commonly excreted in human milk and because of the potential for serious adverse reactions in nursing infants, lactating female patients are excluded from this study. * Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication in tablet form and malabsorption syndrome. * Any mental disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to 28 days after the last dose | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Baseline up to Cycle 1 Day 21 | DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 and defined as any of the following events occurring after first dose of study medication and considered at least possibly-related to study medication. Hematological: grade 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells per cubic millimeter \[cells/mm\^3\]) for 1 week or greater, febrile neutropenia (fever \>=38.5 degree celsius with ANC \<1000/mm\^3), grade 3 (50,000 cells/mm\^3) and grade 4 (\<25,000 cells/mm\^3) thrombocytopenia; Non-Hematologic: grade 3 or 4 nausea, vomiting, or diarrhea and any clinically significant grade 3 or greater non-hematologic toxicity, despite the use of adequate/maximal medical intervention and/or prophylaxis, and any persistent, intolerable PF-04691502 related toxicity which delayed retreatment for \>14 days. |
| Recommended Phase-2 Dose (RP2D) | Baseline up to Cycle 1 Day 21 | RP2D was determined based on the safety profile and pharmacodynamic findings, as per investigator's discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Decay Half-Life (t1/2) | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours (hrs) post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half-life of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeat oral dose administration for 21 days in Cycle 1 (multiple dose PK). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period | AUC (0-∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21 | AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where tau is the dosing interval of 24 hours. It was evaluated following repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK) only. |
| Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8. |
| Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8. |
| Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT | Serum glucose level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8. |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 21 (C1D21) | The pharmacokinetics (PK) of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK). |
| Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT | Serum C-peptide level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8. |
| Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Baseline; 4 hours post-dose on C1D21 | Fresh tumor biopsy samples analysis included assessment of status of proteins indicative of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) related pathways signaling status and cell cycle status. The biomarkers included phosphorylated activated kinase (AKT) S473, AKT T308, signal transducer and activator of transcription 3 (STAT3) and forkhead transcription factor Foxo1 (FKHR) T24/forkhead in rhabdomysacoma-like 1 (FKHRL1) T32. The method of analysis was reverse phase microarray (RPMA). The signal (normalized fluorescence unit \[NFU\]) for each pathway biomarker was normalized against the signal (NFU) for cytokeratin. The final concentration for each pathway biomarker was reported as a cytokeratin normalized fluorescence unit (NFC) value. |
| Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Baseline; pre-dose, 2, 4, 24 hours post-dose on C1D21 | Hair follicle biopsy samples analysis included assessment of status of proteins indicative of PI3K/mTOR related pathways signaling status and cell cycle status. The analytes measured were phosphorylated AKT S473, AKT T308, KI67, STAT3 (Y705) and proline-rich Akt substrate of 40 kilodaltons at Thr246 (PRAS40 T246). The method of analysis was reverse phase microarray (RPMA). The signal for each biomarker expressed as normalized fluorescence intensity (NFI) was normalized by their respective total protein concentration. This normalization was performed by dividing the biomarker NFI by total protein concentration (mg/mL) of the sample printed to give total protein normalized fluorescence unit (NFU). All clinical sample test results are reported in NFU. |
| Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | Baseline; 4 hours post-dose on C1D21 | Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) gene mutation, PIK3CA gene amplification, and phosphatase and tensin homolog (PTEN) protein deficiency status by immunohistochemistry. |
| Number of Participants With Objective Response | Baseline, prior to Day 1 of Cycle every odd-numbered cycle or when progressive disease was suspected | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT | Serum insulin level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on C1D21 | The PK of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants received either PF-04691502 2 mg, 4 mg, 8 mg or 11 mg tablet as a single oral dose in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by same PF-04691502 dose orally once daily continuously in 21 day cycles up to 1 year unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Continuous Dosing Period | Death | 0 | 0 | 6 | 0 |
| Continuous Dosing Period | Lost to Follow-up | 1 | 1 | 9 | 0 |
| Continuous Dosing Period | Other | 1 | 2 | 9 | 3 |
| Continuous Dosing Period | Withdrawal by Subject | 1 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 24 / 26 | 5 / 5 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 15 / 26 | 3 / 5 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 and defined as any of the following events occurring after first dose of study medication and considered at least possibly-related to study medication. Hematological: grade 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells per cubic millimeter \[cells/mm\^3\]) for 1 week or greater, febrile neutropenia (fever \>=38.5 degree celsius with ANC \<1000/mm\^3), grade 3 (50,000 cells/mm\^3) and grade 4 (\<25,000 cells/mm\^3) thrombocytopenia; Non-Hematologic: grade 3 or 4 nausea, vomiting, or diarrhea and any clinically significant grade 3 or greater non-hematologic toxicity, despite the use of adequate/maximal medical intervention and/or prophylaxis, and any persistent, intolerable PF-04691502 related toxicity which delayed retreatment for \>14 days.
Time frame: Baseline up to Cycle 1 Day 21
Population: Safety analysis set included all enrolled participants who started the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04691502 2 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| PF-04691502 4 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| PF-04691502 8 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 participants |
| PF-04691502 11 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to 28 days after the last dose
Population: Safety analysis set included all enrolled participants who started the treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04691502 2 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| PF-04691502 2 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 2 participants |
| PF-04691502 4 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 3 participants |
| PF-04691502 4 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 1 participants |
| PF-04691502 8 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 25 participants |
| PF-04691502 8 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 15 participants |
| PF-04691502 11 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 3 participants |
| PF-04691502 11 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 5 participants |
Primary
Recommended Phase-2 Dose (RP2D)
RP2D was determined based on the safety profile and pharmacodynamic findings, as per investigator's discretion.
Time frame: Baseline up to Cycle 1 Day 21
Population: Safety analysis set included all enrolled participants who started the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04691502 2 mg | Recommended Phase-2 Dose (RP2D) | 8 milligram |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where tau is the dosing interval of 24 hours. It was evaluated following repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK) only.
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21
Population: PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04691502 2 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 371.7 ng*hr/mL | Geometric Coefficient of Variation 5 |
| PF-04691502 4 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 966.4 ng*hr/mL | Geometric Coefficient of Variation 25 |
| PF-04691502 8 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 1287 ng*hr/mL | Geometric Coefficient of Variation 46 |
| PF-04691502 11 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 1020 ng*hr/mL | — |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0-∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only.
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period
Population: PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04691502 2 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 340.4 ng*hr/mL | Geometric Coefficient of Variation 18 |
| PF-04691502 4 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 741.6 ng*hr/mL | Geometric Coefficient of Variation 17 |
| PF-04691502 8 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 1150 ng*hr/mL | Geometric Coefficient of Variation 42 |
| PF-04691502 11 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 1328 ng*hr/mL | Geometric Coefficient of Variation 32 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). It was evaluated following a single oral dose in lead-in-dose period (single dose PK) only.
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period
Population: PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04691502 2 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 330.3 ng*hr/mL | Geometric Coefficient of Variation 20 |
| PF-04691502 4 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 734.4 ng*hr/mL | Geometric Coefficient of Variation 18 |
| PF-04691502 8 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1130 ng*hr/mL | Geometric Coefficient of Variation 41 |
| PF-04691502 11 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1320 ng*hr/mL | Geometric Coefficient of Variation 32 |
Secondary
Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21
Fresh tumor biopsy samples analysis included assessment of status of proteins indicative of phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) related pathways signaling status and cell cycle status. The biomarkers included phosphorylated activated kinase (AKT) S473, AKT T308, signal transducer and activator of transcription 3 (STAT3) and forkhead transcription factor Foxo1 (FKHR) T24/forkhead in rhabdomysacoma-like 1 (FKHRL1) T32. The method of analysis was reverse phase microarray (RPMA). The signal (normalized fluorescence unit \[NFU\]) for each pathway biomarker was normalized against the signal (NFU) for cytokeratin. The final concentration for each pathway biomarker was reported as a cytokeratin normalized fluorescence unit (NFC) value.
Time frame: Baseline; 4 hours post-dose on C1D21
Population: Fresh tumor biopsy analysis set included all enrolled participants in the tumor biopsy cohort who started treatment and had baseline and on-treatment fresh tumor tissue successfully analyzed for at least 1 of the biomarkers. n=participants evaluable at specified time point. Only PF-04691502 8 mg treatment arm was evaluable for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: AKT T308 (n=4) | 102.9 NFC | Standard Deviation 61.87 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: AKT S473 (n=5) | 98.5 NFC | Standard Deviation 100.19 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: FKHR T24 FKHRL1 T32 (n=5) | 193.4 NFC | Standard Deviation 120.5 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: STAT3 (n=5) | 260.9 NFC | Standard Deviation 192.49 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Change at C1D21: AKT S473 (n=5) | -72.6 NFC | Standard Deviation 82.26 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Change at C1D21: AKT T308 (n=4) | -48.6 NFC | Standard Deviation 40.37 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Change at C1D21: FKHR T24 FKHRL1 T32 (n=5) | -81.5 NFC | Standard Deviation 47.7 |
| PF-04691502 2 mg | Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 21 | Change at C1D21: STAT3 (n=5) | -112.2 NFC | Standard Deviation 78.14 |
Secondary
Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21
Hair follicle biopsy samples analysis included assessment of status of proteins indicative of PI3K/mTOR related pathways signaling status and cell cycle status. The analytes measured were phosphorylated AKT S473, AKT T308, KI67, STAT3 (Y705) and proline-rich Akt substrate of 40 kilodaltons at Thr246 (PRAS40 T246). The method of analysis was reverse phase microarray (RPMA). The signal for each biomarker expressed as normalized fluorescence intensity (NFI) was normalized by their respective total protein concentration. This normalization was performed by dividing the biomarker NFI by total protein concentration (mg/mL) of the sample printed to give total protein normalized fluorescence unit (NFU). All clinical sample test results are reported in NFU.
Time frame: Baseline; pre-dose, 2, 4, 24 hours post-dose on C1D21
Population: Hair follicle analysis set included participants with hair follicles collected and analyzed for biomarkers at screening and on treatment. n=participants evaluable at specified time point. Only PF-04691502 8 mg treatment arm was evaluable for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 4 hours: AKT S473 (n=7) | -2.9 NFU | Standard Deviation 6.15 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 24 hours: AKT S473 (n=7) | 3.2 NFU | Standard Deviation 9.46 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 24 hours: PRAS40 (T246) (n=6) | 10.4 NFU | Standard Deviation 45.68 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: AKT S473 (n=10) | 21.7 NFU | Standard Deviation 10.47 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: AKT T308 (n=7) | 50.3 NFU | Standard Deviation 14.33 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: KI67 (n=6) | 117.9 NFU | Standard Deviation 41.19 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: PRAS40 (T246) (n=7) | 136.7 NFU | Standard Deviation 37.37 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Baseline: STAT3 (Y705) (n=7) | 189.8 NFU | Standard Deviation 46.52 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 0 hour: AKT S473 (n=6) | -3.0 NFU | Standard Deviation 8.63 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 0 hour: AKT T308 (n=5) | -5.9 NFU | Standard Deviation 12.21 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 0 hour: KI67 (n=4) | 2.0 NFU | Standard Deviation 36.24 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 0 hour: PRAS40 (T246) (n=6) | -3.7 NFU | Standard Deviation 39.12 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 0 hour: STAT3 (Y705) (n=4) | 2.5 NFU | Standard Deviation 39.98 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 2 hours: AKT S473 (n=9) | -2.5 NFU | Standard Deviation 5.47 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 2 hours: AKT T308 (n=6) | -10.9 NFU | Standard Deviation 13 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 2 hours: KI67 (n=5) | -8.6 NFU | Standard Deviation 32.67 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 2 hours: PRAS40 (T246) (n=5) | -21.2 NFU | Standard Deviation 28.91 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 2 hours: STAT3 (Y705) (n=5) | 21.4 NFU | Standard Deviation 62.76 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 4 hours: AKT T308 (n=5) | 13.6 NFU | Standard Deviation 29.98 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 4 hours: KI67 (n=3) | 27.0 NFU | Standard Deviation 18.39 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 4 hours: PRAS40 (T246) (n=5) | -15.7 NFU | Standard Deviation 23.74 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 4 hours: STAT3 (Y705) (n=5) | -9.3 NFU | Standard Deviation 48.67 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 24 hours: AKT T308 (n=3) | 7.1 NFU | Standard Deviation 14.89 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 24 hours: KI67 (n=4) | -12.2 NFU | Standard Deviation 31.68 |
| PF-04691502 2 mg | Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 21 | Change at 24 hours: STAT3 (Y705) (n=5) | -10.8 NFU | Standard Deviation 65.89 |
Secondary
Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT)
Serum C-peptide level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8.
Time frame: Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT
Population: Serum biomarker analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable at specified time point for each arm, respectively. Results of PF-04691502 2 mg and 4 mg arm not reported because none of the participants were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=13, 1) | 5.2 nanogram per milliliter (ng/mL) | Standard Deviation 3.36 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=1, 0) | 4.9 nanogram per milliliter (ng/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=10, 0) | 6.2 nanogram per milliliter (ng/mL) | Standard Deviation 3.33 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=1, 0) | 4.8 nanogram per milliliter (ng/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=13, 1) | 3.1 nanogram per milliliter (ng/mL) | Standard Deviation 1.79 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=1, 0) | 0.7 nanogram per milliliter (ng/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=8, 0) | 4.5 nanogram per milliliter (ng/mL) | Standard Deviation 3.62 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=12, 0) | 4.4 nanogram per milliliter (ng/mL) | Standard Deviation 3.58 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=1, 0) | 1.5 nanogram per milliliter (ng/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=3, 0) | 2.0 nanogram per milliliter (ng/mL) | Standard Deviation 1.35 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=6, 1) | 3.4 nanogram per milliliter (ng/mL) | Standard Deviation 2.21 |
| PF-04691502 2 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=1, 0) | 5.8 nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=6, 1) | 0.9 nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=13, 1) | 3.7 nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=13, 1) | 2.0 nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=12, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=10, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=8, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=3, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=1, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=1, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=1, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=1, 0) | NA nanogram per milliliter (ng/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum C-peptide at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=1, 0) | NA nanogram per milliliter (ng/mL) | — |
Secondary
Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT)
Serum glucose level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8.
Time frame: Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT
Population: Serum biomarker analysis set included all enrolled participants who started treatment and had baseline and on-treatment serum biomarker samples (insulin, glucose, and c-peptide) successfully analyzed for at least 1 of the biomarkers. n=participants evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=1, 0, 2, 0) | 19.0 milligram per deciliter (mg/dL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=2, 0, 4, 0) | 10.5 milligram per deciliter (mg/dL) | Standard Deviation 2.12 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 7, 0) | 39.0 milligram per deciliter (mg/dL) | Standard Deviation 26.87 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | 21.5 milligram per deciliter (mg/dL) | Standard Deviation 6.36 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 25, 5) | 87.7 milligram per deciliter (mg/dL) | Standard Deviation 3.51 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=2, 0, 4, 0) | 19.0 milligram per deciliter (mg/dL) | Standard Deviation 4.24 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 17, 3) | 33.0 milligram per deciliter (mg/dL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 21, 3) | 16.7 milligram per deciliter (mg/dL) | Standard Deviation 3.79 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=3, 3, 18, 1) | 8.0 milligram per deciliter (mg/dL) | Standard Deviation 13.53 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=1, 0, 1, 0) | 30.0 milligram per deciliter (mg/dL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 14, 1) | 12.0 milligram per deciliter (mg/dL) | Standard Deviation 10.15 |
| PF-04691502 2 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 23, 5) | 14.0 milligram per deciliter (mg/dL) | Standard Deviation 7.55 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 21, 3) | 11.7 milligram per deciliter (mg/dL) | Standard Deviation 19.66 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 25, 5) | 84.3 milligram per deciliter (mg/dL) | Standard Deviation 0.58 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=2, 0, 4, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 23, 5) | 16.7 milligram per deciliter (mg/dL) | Standard Deviation 27.59 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=1, 0, 1, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 14, 1) | 11.7 milligram per deciliter (mg/dL) | Standard Deviation 16.77 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=3, 3, 18, 1) | 4.7 milligram per deciliter (mg/dL) | Standard Deviation 14.57 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=2, 0, 4, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 7, 0) | 15.0 milligram per deciliter (mg/dL) | Standard Deviation 28.28 |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 17, 3) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=1, 0, 2, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=2, 0, 4, 0) | 7.0 milligram per deciliter (mg/dL) | Standard Deviation 41.75 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=1, 0, 1, 0) | 8.0 milligram per deciliter (mg/dL) | — |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 25, 5) | 87.3 milligram per deciliter (mg/dL) | Standard Deviation 16.7 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 23, 5) | 20.0 milligram per deciliter (mg/dL) | Standard Deviation 25.77 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 21, 3) | 17.0 milligram per deciliter (mg/dL) | Standard Deviation 27.23 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=3, 3, 18, 1) | 36.8 milligram per deciliter (mg/dL) | Standard Deviation 37.6 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 14, 1) | 22.6 milligram per deciliter (mg/dL) | Standard Deviation 28.68 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 7, 0) | 36.0 milligram per deciliter (mg/dL) | Standard Deviation 26.34 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=2, 0, 4, 0) | 35.0 milligram per deciliter (mg/dL) | Standard Deviation 32.38 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | 71.3 milligram per deciliter (mg/dL) | Standard Deviation 57.66 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=1, 0, 2, 0) | 50.5 milligram per deciliter (mg/dL) | Standard Deviation 105.36 |
| PF-04691502 8 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 17, 3) | 43.1 milligram per deciliter (mg/dL) | Standard Deviation 94.07 |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=2, 0, 4, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 7, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 14, 1) | 32.0 milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 17, 3) | 13.7 milligram per deciliter (mg/dL) | Standard Deviation 12.22 |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=1, 0, 2, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=3, 3, 18, 1) | 0.0 milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 21, 3) | 99.3 milligram per deciliter (mg/dL) | Standard Deviation 116.43 |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=1, 0, 1, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 23, 5) | 18.8 milligram per deciliter (mg/dL) | Standard Deviation 5.26 |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 25, 5) | 91.8 milligram per deciliter (mg/dL) | Standard Deviation 12.44 |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | NA milligram per deciliter (mg/dL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Glucose at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=2, 0, 4, 0) | NA milligram per deciliter (mg/dL) | — |
Secondary
Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT)
Serum insulin level was measured following 4 hours fasting. EOT data included values from participants who came off-treatment before cycle 8.
Time frame: Baseline, C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and EOT
Population: Serum biomarker analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. n=participants evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | 5.7 micro International Unit/mL (mc IU/mL) | Standard Deviation 1.91 |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=1, 0, 4, 0) | 1.0 micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=2, 3, 13, 0) | 1.4 micro International Unit/mL (mc IU/mL) | Standard Deviation 1.08 |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=1, 0, 4, 0) | 9.1 micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 18, 4) | 6.2 micro International Unit/mL (mc IU/mL) | Standard Deviation 2.67 |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=0, 0, 1, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 10, 1) | -0.1 micro International Unit/mL (mc IU/mL) | Standard Deviation 8.15 |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 10, 2) | 9.0 micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 16, 3) | 5.6 micro International Unit/mL (mc IU/mL) | Standard Deviation 2.32 |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=0, 0, 2, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 4, 0) | 36.0 micro International Unit/mL (mc IU/mL) | Standard Deviation 45.21 |
| PF-04691502 2 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 17, 2) | 7.2 micro International Unit/mL (mc IU/mL) | Standard Deviation 4.17 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 4, 0) | 14.8 micro International Unit/mL (mc IU/mL) | Standard Deviation 16.33 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=1, 0, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 17, 2) | 38.2 micro International Unit/mL (mc IU/mL) | Standard Deviation 56.39 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=1, 0, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 16, 3) | 8.6 micro International Unit/mL (mc IU/mL) | Standard Deviation 6.17 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 10, 2) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=0, 0, 1, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=2, 3, 13, 0) | 11.4 micro International Unit/mL (mc IU/mL) | Standard Deviation 8.17 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 10, 1) | 12.0 micro International Unit/mL (mc IU/mL) | Standard Deviation 6.64 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 18, 4) | 5.8 micro International Unit/mL (mc IU/mL) | Standard Deviation 3.72 |
| PF-04691502 4 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=0, 0, 2, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 16, 3) | 25.2 micro International Unit/mL (mc IU/mL) | Standard Deviation 33.35 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | 21.2 micro International Unit/mL (mc IU/mL) | Standard Deviation 14.38 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 17, 2) | 28.2 micro International Unit/mL (mc IU/mL) | Standard Deviation 27.34 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 18, 4) | 8.0 micro International Unit/mL (mc IU/mL) | Standard Deviation 5.62 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=2, 3, 13, 0) | 26.1 micro International Unit/mL (mc IU/mL) | Standard Deviation 17.25 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 10, 1) | 12.3 micro International Unit/mL (mc IU/mL) | Standard Deviation 10.95 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 4, 0) | -1.0 micro International Unit/mL (mc IU/mL) | Standard Deviation 5.92 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=1, 0, 4, 0) | 20.3 micro International Unit/mL (mc IU/mL) | Standard Deviation 15.72 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=1, 0, 4, 0) | 13.7 micro International Unit/mL (mc IU/mL) | Standard Deviation 10.53 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=0, 0, 2, 0) | 10.4 micro International Unit/mL (mc IU/mL) | Standard Deviation 14.71 |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=0, 0, 1, 0) | 8.4 micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 8 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 10, 2) | 7.8 micro International Unit/mL (mc IU/mL) | Standard Deviation 14.05 |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C3D1 (n=2, 2, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D15 (n=3, 3, 10, 1) | 29.2 micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Baseline (n=3, 3, 18, 4) | 21.4 micro International Unit/mL (mc IU/mL) | Standard Deviation 25.7 |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C7D1 (n=0, 0, 2, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C2D1 (n=2, 3, 13, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D15 (n=3, 3, 16, 3) | 60.5 micro International Unit/mL (mc IU/mL) | Standard Deviation 30.75 |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at End of Treatment (n=1, 0, 10, 2) | 13.1 micro International Unit/mL (mc IU/mL) | Standard Deviation 3.89 |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C8D1 (n=0, 0, 1, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C5D1 (n=2, 0, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C4D1 (n=1, 0, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C1D8 (n=3, 3, 17, 2) | 15.4 micro International Unit/mL (mc IU/mL) | Standard Deviation 15.13 |
| PF-04691502 11 mg | Change From Baseline in Serum Insulin at Cycle 1 Day 8 (C1D8), C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1 and End of Treatment (EOT) | Change at C6D1 (n=1, 0, 4, 0) | NA micro International Unit/mL (mc IU/mL) | — |
Secondary
Maximum Observed Plasma Concentration (Cmax)
The pharmacokinetics (PK) of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK).
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 21 (C1D21)
Population: PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. n=participants evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Maximum Observed Plasma Concentration (Cmax) | Single Dose: Cmax (n=3, 3, 26, 5) | 18.07 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| PF-04691502 2 mg | Maximum Observed Plasma Concentration (Cmax) | Multiple Dose: Cmax (n=3, 3, 20, 1) | 26.30 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| PF-04691502 4 mg | Maximum Observed Plasma Concentration (Cmax) | Multiple Dose: Cmax (n=3, 3, 20, 1) | 78.91 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| PF-04691502 4 mg | Maximum Observed Plasma Concentration (Cmax) | Single Dose: Cmax (n=3, 3, 26, 5) | 58.29 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-04691502 8 mg | Maximum Observed Plasma Concentration (Cmax) | Single Dose: Cmax (n=3, 3, 26, 5) | 66.40 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| PF-04691502 8 mg | Maximum Observed Plasma Concentration (Cmax) | Multiple Dose: Cmax (n=3, 3, 20, 1) | 102.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| PF-04691502 11 mg | Maximum Observed Plasma Concentration (Cmax) | Single Dose: Cmax (n=3, 3, 26, 5) | 82.51 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| PF-04691502 11 mg | Maximum Observed Plasma Concentration (Cmax) | Multiple Dose: Cmax (n=3, 3, 20, 1) | 89.8 nanogram per milliliter (ng/mL) | — |
Secondary
Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF)
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8.
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT
Population: QTc analysis set included all enrolled participants who had at least 1 ECG assessment after receiving PF-04691502.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04691502 2 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change >=60 sec) | 0 participants |
| PF-04691502 2 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | MaximumQTcF Interval Increase(Change>=30to<60msec) | 1 participants |
| PF-04691502 2 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change <30 msec) | 2 participants |
| PF-04691502 4 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change >=60 sec) | 0 participants |
| PF-04691502 4 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change <30 msec) | 3 participants |
| PF-04691502 4 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | MaximumQTcF Interval Increase(Change>=30to<60msec) | 0 participants |
| PF-04691502 8 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change <30 msec) | 19 participants |
| PF-04691502 8 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change >=60 sec) | 0 participants |
| PF-04691502 8 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | MaximumQTcF Interval Increase(Change>=30to<60msec) | 7 participants |
| PF-04691502 11 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | MaximumQTcF Interval Increase(Change>=30to<60msec) | 0 participants |
| PF-04691502 11 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change >=60 sec) | 0 participants |
| PF-04691502 11 mg | Number of Participants With Increase From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval Increase (Change <30 msec) | 5 participants |
Secondary
Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF)
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2-4 minutes) were performed and average calculated. QT interval is the time between the start of the Q wave and the end of the T wave in the cardiac electrical cycle. QTcF is the QT interval corrected for heart rate. Corrected QT interval using Fridericia's heart rate correction formula: QTcF = QT/RR\^1/3, where RR=RR interval in seconds. End of treatment (EOT) data included values from participants who came off-treatment before cycle 8.
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 8, 24, 48, hrs post-dose in Lead-in period; 1 hour post-dose on C1D8, C1D15; 1, 2, 4, 8 hours post-dose on C1D21; 1 hour post-dose C2D1, C2D15, D1 of subsequent cycles up to C8; EOT
Population: QTc analysis set included all enrolled participants had at least 1 ECG assessment after receiving PF-04691502.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04691502 2 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (<450 msec) | 2 participants |
| PF-04691502 2 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (450 to <480 msec) | 1 participants |
| PF-04691502 2 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (480 to <500 msec) | 0 participants |
| PF-04691502 2 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (>=500 msec) | 0 participants |
| PF-04691502 4 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (>=500 msec) | 0 participants |
| PF-04691502 4 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (480 to <500 msec) | 0 participants |
| PF-04691502 4 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (450 to <480 msec) | 0 participants |
| PF-04691502 4 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (<450 msec) | 3 participants |
| PF-04691502 8 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (480 to <500 msec) | 3 participants |
| PF-04691502 8 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (>=500 msec) | 0 participants |
| PF-04691502 8 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (450 to <480 msec) | 5 participants |
| PF-04691502 8 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (<450 msec) | 18 participants |
| PF-04691502 11 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (450 to <480 msec) | 3 participants |
| PF-04691502 11 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (<450 msec) | 2 participants |
| PF-04691502 11 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (>=500 msec) | 0 participants |
| PF-04691502 11 mg | Number of Participants With Maximum Post-dose QT Interval Corrected Using Fridericia's Formula (QTcF) | Maximum QTcF Interval (480 to <500 msec) | 0 participants |
Secondary
Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue
Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) gene mutation, PIK3CA gene amplification, and phosphatase and tensin homolog (PTEN) protein deficiency status by immunohistochemistry.
Time frame: Baseline; 4 hours post-dose on C1D21
Population: Baseline tumor tissue biomarker analysis set: all enrolled participants who started treatment, had baseline tumor tissues (archived paraffin block/unstained slides/fresh tumor tissue) analyzed for at least 1 of biomarkers. N (number of participants analyzed)=participants evaluable for this measure. n=participants evaluable at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04691502 2 mg | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | PTEN status: Absent (n=18) | 9 participants |
| PF-04691502 2 mg | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | PIK3CA amplification: Positive (n=17) | 2 participants |
| PF-04691502 2 mg | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | PTEN status: Present (n=18) | 9 participants |
| PF-04691502 2 mg | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | PIK3CA amplification: Negative (n=17) | 15 participants |
| PF-04691502 2 mg | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | PIK3CA mutation status: Detectable (n=17) | 3 participants |
| PF-04691502 2 mg | Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue | PIK3CA mutation status: Undetectable (n=17) | 14 participants |
Secondary
Number of Participants With Objective Response
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline, prior to Day 1 of Cycle every odd-numbered cycle or when progressive disease was suspected
Population: Response analysis set included all participants who started treatment and had an adequate baseline tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04691502 2 mg | Number of Participants With Objective Response | 0 participants |
| PF-04691502 4 mg | Number of Participants With Objective Response | 0 participants |
| PF-04691502 8 mg | Number of Participants With Objective Response | 0 participants |
| PF-04691502 11 mg | Number of Participants With Objective Response | 0 participants |
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half-life of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeat oral dose administration for 21 days in Cycle 1 (multiple dose PK).
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours (hrs) post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hrs post-dose on C1D21
Population: PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. n=participants evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04691502 2 mg | Plasma Decay Half-Life (t1/2) | Single Dose: t1/2 (n=3, 3, 26, 5) | 13.23 hours | Standard Deviation 2.8746 |
| PF-04691502 2 mg | Plasma Decay Half-Life (t1/2) | Multiple Dose: t1/2 (n=1, 0, 5, 1) | 9.19 hours | — |
| PF-04691502 4 mg | Plasma Decay Half-Life (t1/2) | Multiple Dose: t1/2 (n=1, 0, 5, 1) | NA hours | — |
| PF-04691502 4 mg | Plasma Decay Half-Life (t1/2) | Single Dose: t1/2 (n=3, 3, 26, 5) | 10.87 hours | Standard Deviation 0.90738 |
| PF-04691502 8 mg | Plasma Decay Half-Life (t1/2) | Single Dose: t1/2 (n=3, 3, 26, 5) | 13.77 hours | Standard Deviation 5.215 |
| PF-04691502 8 mg | Plasma Decay Half-Life (t1/2) | Multiple Dose: t1/2 (n=1, 0, 5, 1) | 8.984 hours | Standard Deviation 0.7084 |
| PF-04691502 11 mg | Plasma Decay Half-Life (t1/2) | Single Dose: t1/2 (n=3, 3, 26, 5) | 11.66 hours | Standard Deviation 1.7315 |
| PF-04691502 11 mg | Plasma Decay Half-Life (t1/2) | Multiple Dose: t1/2 (n=1, 0, 5, 1) | 7.83 hours | — |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
The PK of PF-04691502 was assessed following a single oral dose administration in lead-in-dose period (single dose PK) and repeated oral dose administration for 21 days in Cycle 1 (multiple dose PK).
Time frame: Pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72, 96 hours post-dose in Lead-in period; pre-dose, 30 minutes, 1, 2, 4, 6, 8, 24 hours post-dose on C1D21
Population: PK population included all randomized participants who received treatment and had at least 1 of the PK parameters of interest estimated. n=participants evaluable at specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-04691502 2 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Single Dose: Tmax (n=3, 3, 26, 5) | 4.00 hours |
| PF-04691502 2 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Multiple Dose: Tmax (n=3, 3, 20, 1) | 2.00 hours |
| PF-04691502 4 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Multiple Dose: Tmax (n=3, 3, 20, 1) | 2.00 hours |
| PF-04691502 4 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Single Dose: Tmax (n=3, 3, 26, 5) | 0.683 hours |
| PF-04691502 8 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Single Dose: Tmax (n=3, 3, 26, 5) | 2.03 hours |
| PF-04691502 8 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Multiple Dose: Tmax (n=3, 3, 20, 1) | 2.01 hours |
| PF-04691502 11 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Single Dose: Tmax (n=3, 3, 26, 5) | 4.07 hours |
| PF-04691502 11 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Multiple Dose: Tmax (n=3, 3, 20, 1) | 2.15 hours |