Astrocytoma, Malignant Glioma, Oligodendroglioma
Conditions
Keywords
GBM, malignant glioma, glioma, anaplastic glioma, astrocytoma, IDO, IDO1, PF-06840003
Brief summary
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.
Interventions
DRUGPF-06840003
Daily Oral PF-06840003
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of WHO Grade IV glioblastoma or WHO Grade III anaplastic gliomas * For patients with Grade IV GBM, recurrent disease at the time of the first or second recurrence or progression. For patients with Grade III anaplastic gliomas, recurrent disease at the time of at least a first recurrence but no more than a fourth recurrence or progression * Karnofsky performance score greater than or equal to 70% * Adequate bone marrow, kidney and liver function
Exclusion criteria
* History of CNS bleeding within 6 months of registration * Previous anti-angiogenics or anti-vascular endothelial growth factor within 12 months of registration * Requires treatment with high dose systemic corticosteroids defined as \>2 mg/day * Radiation therapy within 12 weeks of registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1] | Baseline to Day 28 | DLTs: Any of the following adverse events (AE) occurring in the first cycle of treatment, unless there is a clear alternative explanation. Hematologic: Grade (Gr) 4 neutropenia lasting \>=5 days; febrile neutropenia; Gr\>=3 neutropenic with infection; Gr\>=3 thrombocytopenia with bleeding; Gr 4 thrombocytopenia. Non-Hematologic: Any toxicity attributable to PF-06840003 that resulted in administration of less than 80% of the planned doses during Cycle 1; Gr 4 non-hematologic AE; Gr 3 AE lasting \>7 days despite optimal supportive care; Gr 3 central nervous system (CNS) AE regardless of duration; Gr 3 QTc prolongation (QTc \>500 milliseconds) (a DLT only if persisting after correction of any reversible causes); Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3\*upper limit of normal (ULN) and total bilirubin \>2\*ULN. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | Baseline up to 1 year | An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those with initial onset or increasing in severity after the first dose of study treatment. |
| Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Baseline up to 1 year | Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Baseline up to 1 year | Following parameters were analyzed for chemistry laboratory test: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, and phosphorous or phosphate. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here. |
| Number of Participants With Clinically Significant Findings in Vital Signs [Part 1] | Baseline up to 1 year | Vital signs included measurements of blood pressure and temperature (oral, tympanic, temporal or axillary). The investigator judged any clinically significant vital signs findings. |
| Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data. |
| Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence. |
| Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | AUClast of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method. |
| Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method. |
| Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC\*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose | AUCinf of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUClast + (Clast/kel), where AUClast is the area under the concentration-time profile from time zero to the time of the last quantifiable concentration, Clast is the predicted serum concentration at the last quantifiable time point estimated from the log linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data. |
| Objective Response Rate (ORR) [Part 1] | Weeks 8, 16, and 24 | Objective response rate (ORR), defined as the percentage of patients achieving complete response (CR) or partial response (PR) as assessed by Macdonald criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. |
| Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method. |
| Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Cmin of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data. |
| Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Cav of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data. |
| Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf). |
| Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC\*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Rac of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCtau (single dose). |
| Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Rss of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCinf (single dose). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Steady-State Trough Level Ratio [Part 1] | Baseline and Day 15 | Steady-State trough level ratio was determined by cerebrospinal fluid (CSF)/Plasma. CSF/Plasma ratio was calculated based on the unbound concentration of each analyte. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. |
| Plasma Kynurenine and Tryptophan [Part 1] | Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose | The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method. |
| Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1] | Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose | The Kynurenine/Tryptophan ratio was determined by 1000\*Kynurenine/Tryptophan. |
| Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post | Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence. |
| Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Weeks 8, 16, and 24 | Disease control rate (DCR) was defined as the percentage of patients achieving CR, PR, or stable disease (SD). Overall DCR was based on iRANO criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; SD: does not qualify for CR, PR, or progression disease, and stable clinically. |
| Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Baseline up to 1 year | Following parameters were analyzed for hematology laboratory test: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute basophils. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here. |
Countries
United States
Participant flow
Pre-assignment details
After reviewing efficacy, safety, PK and PD of all available data from enrolled patients, the Sponsor decided to prematurely terminate the study and not to pursue marketing approval for PF-06840003 in the indication of malignant glioma. Part 2 of the study was not initiated.
Participants by arm
| Arm | Count |
|---|---|
| PF-06840003 125 MG QD PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | 2 |
| PF-06840003 250 MG QD PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | 4 |
| PF-06840003 250 MG BID PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | 3 |
| PF-06840003 500 MG BID PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Other | 0 | 0 | 0 | 2 |
| Overall Study | Subject refused further follow-up | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 19.1 | 51.8 years STANDARD_DEVIATION 14.5 | 49.3 years STANDARD_DEVIATION 12.1 | 58.1 years STANDARD_DEVIATION 14.6 | 53.5 years STANDARD_DEVIATION 14.1 |
| Age, Customized 18-44 Years | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Age, Customized 45-64 Years | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 7 Participants |
| Age, Customized >=65 Years | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 4 Participants | 3 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 2 Participants | 5 Participants | 12 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 | 0 / 2 | 0 / 4 | 0 / 3 | 0 / 8 |
| other Total, other adverse events | 2 / 2 | 4 / 4 | 3 / 3 | 8 / 8 |
| serious Total, serious adverse events | 0 / 2 | 1 / 4 | 0 / 3 | 3 / 8 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]
DLTs: Any of the following adverse events (AE) occurring in the first cycle of treatment, unless there is a clear alternative explanation. Hematologic: Grade (Gr) 4 neutropenia lasting \>=5 days; febrile neutropenia; Gr\>=3 neutropenic with infection; Gr\>=3 thrombocytopenia with bleeding; Gr 4 thrombocytopenia. Non-Hematologic: Any toxicity attributable to PF-06840003 that resulted in administration of less than 80% of the planned doses during Cycle 1; Gr 4 non-hematologic AE; Gr 3 AE lasting \>7 days despite optimal supportive care; Gr 3 central nervous system (CNS) AE regardless of duration; Gr 3 QTc prolongation (QTc \>500 milliseconds) (a DLT only if persisting after correction of any reversible causes); Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3\*upper limit of normal (ULN) and total bilirubin \>2\*ULN.
Time frame: Baseline to Day 28
Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06840003 125 MG QD | Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1] | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1] | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1] | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1] | 1 Participants |
Primary
Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Time frame: Baseline up to 1 year
Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06840003 125 MG QD | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 3 or 4 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 5 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 5 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 3 or 4 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 3 or 4 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 5 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 3 or 4 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Grade 5 | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.
Time frame: Baseline up to 1 year
Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06840003 125 MG QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | Treatment-related TEAEs | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | All-causality TEAEs | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | All-causality TEAEs | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | Treatment-related TEAEs | 4 Participants |
| PF-06840003 250 MG BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | Treatment-related TEAEs | 2 Participants |
| PF-06840003 250 MG BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | All-causality TEAEs | 3 Participants |
| PF-06840003 500 MG BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | Treatment-related TEAEs | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] | All-causality TEAEs | 8 Participants |
Secondary
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]
Disease control rate (DCR) was defined as the percentage of patients achieving CR, PR, or stable disease (SD). Overall DCR was based on iRANO criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; SD: does not qualify for CR, PR, or progression disease, and stable clinically.
Time frame: Weeks 8, 16, and 24
Population: The analysis population included all the participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06840003 125 MG QD | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 24 | 0.0 percentage of participants |
| PF-06840003 125 MG QD | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 16 | 50.0 percentage of participants |
| PF-06840003 125 MG QD | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 8 | 50.0 percentage of participants |
| PF-06840003 250 MG QD | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 24 | 0.0 percentage of participants |
| PF-06840003 250 MG QD | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 8 | 50.0 percentage of participants |
| PF-06840003 250 MG QD | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 16 | 0.0 percentage of participants |
| PF-06840003 250 MG BID | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 8 | 33.3 percentage of participants |
| PF-06840003 250 MG BID | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 24 | 0.0 percentage of participants |
| PF-06840003 250 MG BID | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 16 | 66.7 percentage of participants |
| PF-06840003 500 MG BID | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 16 | 25.0 percentage of participants |
| PF-06840003 500 MG BID | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 24 | 25.0 percentage of participants |
| PF-06840003 500 MG BID | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] | Week 8 | 25.0 percentage of participants |
Secondary
Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf).
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA mL/min | — |
| PF-06840003 125 MG QD | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA mL/min | — |
| PF-06840003 250 MG QD | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 399.1 mL/min | Geometric Coefficient of Variation 64 |
| PF-06840003 250 MG QD | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 624.2 mL/min | Geometric Coefficient of Variation 75 |
| PF-06840003 250 MG BID | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 327.6 mL/min | Geometric Coefficient of Variation 50 |
| PF-06840003 250 MG BID | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 198.2 mL/min | Geometric Coefficient of Variation 50 |
| PF-06840003 500 MG BID | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 408.3 mL/min | Geometric Coefficient of Variation 96 |
| PF-06840003 500 MG BID | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 259.5 mL/min | Geometric Coefficient of Variation 89 |
Secondary
Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC\*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where Vz/F was determined.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 184.5 Liter |
| PF-06840003 125 MG QD | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 102.6 Liter |
| PF-06840003 250 MG QD | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 117 Liter |
| PF-06840003 250 MG QD | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 216 Liter |
| PF-06840003 250 MG BID | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 128 Liter |
| PF-06840003 250 MG BID | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 72.6 Liter |
| PF-06840003 500 MG BID | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 270.5 Liter |
| PF-06840003 500 MG BID | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 162 Liter |
Secondary
Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ng*hr/mL | — |
| PF-06840003 125 MG QD | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ng*hr/mL | — |
| PF-06840003 250 MG QD | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 10440 ng*hr/mL | Geometric Coefficient of Variation 64 |
| PF-06840003 250 MG QD | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 6680 ng*hr/mL | Geometric Coefficient of Variation 75 |
| PF-06840003 250 MG BID | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 21020 ng*hr/mL | Geometric Coefficient of Variation 50 |
| PF-06840003 250 MG BID | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 12730 ng*hr/mL | Geometric Coefficient of Variation 50 |
| PF-06840003 500 MG BID | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 20410 ng*hr/mL | Geometric Coefficient of Variation 96 |
| PF-06840003 500 MG BID | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 32080 ng*hr/mL | Geometric Coefficient of Variation 89 |
Secondary
Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1]
Cav of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ng/mL | — |
| PF-06840003 125 MG QD | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ng/mL | — |
| PF-06840003 250 MG QD | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 435.1 ng/mL | Geometric Coefficient of Variation 64 |
| PF-06840003 250 MG QD | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 278 ng/mL | Geometric Coefficient of Variation 75 |
| PF-06840003 250 MG BID | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1060 ng/mL | Geometric Coefficient of Variation 50 |
| PF-06840003 250 MG BID | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1755 ng/mL | Geometric Coefficient of Variation 49 |
| PF-06840003 500 MG BID | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1702 ng/mL | Geometric Coefficient of Variation 96 |
| PF-06840003 500 MG BID | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2673 ng/mL | Geometric Coefficient of Variation 89 |
Secondary
Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1]
Cmin of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ng/mL | — |
| PF-06840003 125 MG QD | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ng/mL | — |
| PF-06840003 250 MG QD | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 21.75 ng/mL | Standard Deviation 27.298 |
| PF-06840003 250 MG QD | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 15.85 ng/mL | Standard Deviation 21.622 |
| PF-06840003 250 MG BID | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 687.3 ng/mL | Standard Deviation 409.76 |
| PF-06840003 250 MG BID | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1079 ng/mL | Standard Deviation 587.86 |
| PF-06840003 500 MG BID | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1611 ng/mL | Standard Deviation 1749.7 |
| PF-06840003 500 MG BID | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2308 ng/mL | Standard Deviation 2161.3 |
Secondary
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ng/mL | — |
| PF-06840003 125 MG QD | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ng/mL | — |
| PF-06840003 250 MG QD | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1334 ng/mL | Geometric Coefficient of Variation 5 |
| PF-06840003 250 MG QD | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 779.3 ng/mL | Geometric Coefficient of Variation 9 |
| PF-06840003 250 MG BID | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1763 ng/mL | Geometric Coefficient of Variation 25 |
| PF-06840003 250 MG BID | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2810 ng/mL | Geometric Coefficient of Variation 24 |
| PF-06840003 500 MG BID | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2474 ng/mL | Geometric Coefficient of Variation 66 |
| PF-06840003 500 MG BID | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 3978 ng/mL | Geometric Coefficient of Variation 58 |
Secondary
Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1]
Rac of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCtau (single dose).
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ratio | — |
| PF-06840003 125 MG QD | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ratio | — |
| PF-06840003 250 MG QD | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1.163 ratio | Geometric Coefficient of Variation 31 |
| PF-06840003 250 MG QD | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.244 ratio | Geometric Coefficient of Variation 31 |
| PF-06840003 250 MG BID | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.670 ratio | Geometric Coefficient of Variation 45 |
| PF-06840003 250 MG BID | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1.717 ratio | Geometric Coefficient of Variation 45 |
| PF-06840003 500 MG BID | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2.359 ratio | Geometric Coefficient of Variation 45 |
| PF-06840003 500 MG BID | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.304 ratio | Geometric Coefficient of Variation 41 |
Secondary
Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1]
Rss of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCinf (single dose). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where Rss was determined.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ratio | — |
| PF-06840003 125 MG QD | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ratio | — |
| PF-06840003 250 MG QD | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.289 ratio | Geometric Coefficient of Variation 37 |
| PF-06840003 250 MG QD | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1.266 ratio | Geometric Coefficient of Variation 31 |
| PF-06840003 500 MG BID | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.961 ratio | Geometric Coefficient of Variation 72 |
| PF-06840003 500 MG BID | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1.895 ratio | Geometric Coefficient of Variation 61 |
Secondary
Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where t1/2 was determined.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 5.58 hr |
| PF-06840003 125 MG QD | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 5.505 hr |
| PF-06840003 250 MG QD | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.61 hr |
| PF-06840003 250 MG QD | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2.90 hr |
| PF-06840003 250 MG BID | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2.68 hr |
| PF-06840003 250 MG BID | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.50 hr |
| PF-06840003 500 MG BID | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2.885 hr |
| PF-06840003 500 MG BID | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.685 hr |
Secondary
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.
Time frame: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-06840003 125 MG QD | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 3.00 hr |
| PF-06840003 125 MG QD | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 3.00 hr |
| PF-06840003 250 MG QD | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 3.03 hr |
| PF-06840003 250 MG QD | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 3.03 hr |
| PF-06840003 250 MG BID | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2.00 hr |
| PF-06840003 250 MG BID | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.00 hr |
| PF-06840003 500 MG BID | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 3.02 hr |
| PF-06840003 500 MG BID | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 3.95 hr |
Secondary
Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Following parameters were analyzed for chemistry laboratory test: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, and phosphorous or phosphate. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.
Time frame: Baseline up to 1 year
Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 0 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 1 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 4 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 1 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 4 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 3 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Bilirubin (total), Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 0 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 0 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 3 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 3 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 1 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 3 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 4 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 1 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 3 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 0 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 3 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 4 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 2 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Bilirubin (total), Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 0 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 1 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 0 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 3 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 1 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 1 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 3 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 3 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 1 | 2 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 3 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 0 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 4 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 1 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 0 | 2 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 0 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 1 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 1 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 4 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 3 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Bilirubin (total), Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 0 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 1 | 2 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 0 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 3 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 3 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 4 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 0 | 6 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 2 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 4 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 0 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 0 | 6 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 0 | 6 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 1 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 1 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperkalemia, Grade 3 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 0 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 1 | 4 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypocalcemia, Grade 2 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 2 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 1 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypermagnesemia, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | ALT, Grade 1 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoglycemia, Grade 0 | 8 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypernatremia, Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 3 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | AST, Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 1 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Alkaline phosphatase, Grade 1 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypomagnesemia, Grade 0 | 8 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyperglycemia, Grade 1 | 4 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 0 | 5 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 3 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypophosphatemia, Grade 2 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 1 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypercalcemia, Grade 0 | 8 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hyponatremia, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Bilirubin (total), Grade 0 | 8 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypoalbuminemia, Grade 2 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Creatinine, Grade 2 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hypokalemia, Grade 0 | 4 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]
Vital signs included measurements of blood pressure and temperature (oral, tympanic, temporal or axillary). The investigator judged any clinically significant vital signs findings.
Time frame: Baseline up to 1 year
Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06840003 125 MG QD | Number of Participants With Clinically Significant Findings in Vital Signs [Part 1] | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Clinically Significant Findings in Vital Signs [Part 1] | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Clinically Significant Findings in Vital Signs [Part 1] | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Clinically Significant Findings in Vital Signs [Part 1] | 0 Participants |
Secondary
Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
Following parameters were analyzed for hematology laboratory test: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute basophils. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.
Time frame: Baseline up to 1 year
Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 0 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 0 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 3 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 1 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 2 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 2 | 0 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 1 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hemoglobin increased, Grade 0 | 2 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 0 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 1 | 1 Participants |
| PF-06840003 125 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphocyte count increased, Grade 0 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphocyte count increased, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 0 | 3 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 0 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 3 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 2 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 1 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 0 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 0 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 1 | 2 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 1 | 1 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hemoglobin increased, Grade 0 | 4 Participants |
| PF-06840003 250 MG QD | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 1 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 2 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 3 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 0 | 2 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 2 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 0 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 1 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 2 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hemoglobin increased, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphocyte count increased, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 0 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 2 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 0 | 3 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 1 | 0 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 0 | 1 Participants |
| PF-06840003 250 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 0 | 7 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 2 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 1 | 6 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Anemia, Grade 0 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 2 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 0 | 5 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | WBC, Grade 0 | 6 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 1 | 1 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Platelets, Grade 1 | 3 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Neutrophils (absolute), Grade 2 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 2 | 0 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 0 | 5 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphopenia, Grade 3 | 2 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Lymphocyte count increased, Grade 0 | 8 Participants |
| PF-06840003 500 MG BID | Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1] | Hemoglobin increased, Grade 0 | 8 Participants |
Secondary
Objective Response Rate (ORR) [Part 1]
Objective response rate (ORR), defined as the percentage of patients achieving complete response (CR) or partial response (PR) as assessed by Macdonald criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks.
Time frame: Weeks 8, 16, and 24
Population: The analysis population included all the participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06840003 125 MG QD | Objective Response Rate (ORR) [Part 1] | Week 24 | 0.00 Percentage of Participants |
| PF-06840003 125 MG QD | Objective Response Rate (ORR) [Part 1] | Week 8 | 0.00 Percentage of Participants |
| PF-06840003 125 MG QD | Objective Response Rate (ORR) [Part 1] | Week 16 | 0.00 Percentage of Participants |
| PF-06840003 250 MG QD | Objective Response Rate (ORR) [Part 1] | Week 16 | 0.00 Percentage of Participants |
| PF-06840003 250 MG QD | Objective Response Rate (ORR) [Part 1] | Week 8 | 0.00 Percentage of Participants |
| PF-06840003 250 MG QD | Objective Response Rate (ORR) [Part 1] | Week 24 | 0.00 Percentage of Participants |
| PF-06840003 250 MG BID | Objective Response Rate (ORR) [Part 1] | Week 24 | 0.00 Percentage of Participants |
| PF-06840003 250 MG BID | Objective Response Rate (ORR) [Part 1] | Week 8 | 0.00 Percentage of Participants |
| PF-06840003 250 MG BID | Objective Response Rate (ORR) [Part 1] | Week 16 | 0.00 Percentage of Participants |
| PF-06840003 500 MG BID | Objective Response Rate (ORR) [Part 1] | Week 16 | 0.00 Percentage of Participants |
| PF-06840003 500 MG BID | Objective Response Rate (ORR) [Part 1] | Week 8 | 0.00 Percentage of Participants |
| PF-06840003 500 MG BID | Objective Response Rate (ORR) [Part 1] | Week 24 | 0.00 Percentage of Participants |
Secondary
Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]
The Kynurenine/Tryptophan ratio was determined by 1000\*Kynurenine/Tryptophan.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose
Population: The Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population on Cycle 1 Day. The Number Analyzed represents the number of participants contributing to the summary statistics at the end of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-06840003 125 MG QD | Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1] | 38.467 ratio | Standard Deviation 0.6791 |
| PF-06840003 250 MG QD | Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1] | 53.066 ratio | Standard Deviation 24.9722 |
| PF-06840003 250 MG BID | Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1] | 25.854 ratio | Standard Deviation 7.6209 |
| PF-06840003 500 MG BID | Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1] | 42.463 ratio | — |
Secondary
Plasma Kynurenine and Tryptophan [Part 1]
The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method.
Time frame: Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose
Population: The analysis population was the total number of participants in the treatment group in the indicated population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Plasma Kynurenine and Tryptophan [Part 1] | Kynurenine | 1.545 micromolar | Standard Deviation 0.2051 |
| PF-06840003 125 MG QD | Plasma Kynurenine and Tryptophan [Part 1] | Tryptophan | 48.15 micromolar | Standard Deviation 4.596 |
| PF-06840003 250 MG QD | Plasma Kynurenine and Tryptophan [Part 1] | Tryptophan | 29.55 micromolar | Standard Deviation 4.611 |
| PF-06840003 250 MG QD | Plasma Kynurenine and Tryptophan [Part 1] | Kynurenine | 2.185 micromolar | Standard Deviation 1.7443 |
| PF-06840003 250 MG BID | Plasma Kynurenine and Tryptophan [Part 1] | Kynurenine | 1.144 micromolar | Standard Deviation 0.1479 |
| PF-06840003 250 MG BID | Plasma Kynurenine and Tryptophan [Part 1] | Tryptophan | 36.77 micromolar | Standard Deviation 7.681 |
| PF-06840003 500 MG BID | Plasma Kynurenine and Tryptophan [Part 1] | Kynurenine | 1.523 micromolar | Standard Deviation 0.4321 |
| PF-06840003 500 MG BID | Plasma Kynurenine and Tryptophan [Part 1] | Tryptophan | 33.10 micromolar | Standard Deviation 4.59 |
Secondary
Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1]
CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where CL/F was determined.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA Milliliter per minute (mL/min) | — |
| PF-06840003 125 MG QD | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA Milliliter per minute (mL/min) | — |
| PF-06840003 250 MG QD | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 751.6 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 85 |
| PF-06840003 250 MG QD | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 454.6 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 69 |
| PF-06840003 500 MG BID | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1561 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 40 |
| PF-06840003 500 MG BID | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 965.4 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 39 |
Secondary
Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1]
Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC\*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where Vz/F was determined.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA Liter | — |
| PF-06840003 125 MG QD | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA Liter | — |
| PF-06840003 250 MG QD | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 228.4 Liter | Geometric Coefficient of Variation 27 |
| PF-06840003 250 MG QD | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 129.3 Liter | Geometric Coefficient of Variation 12 |
| PF-06840003 500 MG BID | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 277.2 Liter | Geometric Coefficient of Variation 20 |
| PF-06840003 500 MG BID | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 159.6 Liter | Geometric Coefficient of Variation 25 |
Secondary
Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1]
AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA nanogram*hour per milliliter (ng*hr/mL) | — |
| PF-06840003 125 MG QD | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA nanogram*hour per milliliter (ng*hr/mL) | — |
| PF-06840003 250 MG QD | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 8999 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
| PF-06840003 250 MG QD | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 5356 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 60 |
| PF-06840003 250 MG BID | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 7606 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 11 |
| PF-06840003 250 MG BID | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 12280 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| PF-06840003 500 MG BID | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 13910 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
| PF-06840003 500 MG BID | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 8653 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 57 |
Secondary
Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1]
AUCinf of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUClast + (Clast/kel), where AUClast is the area under the concentration-time profile from time zero to the time of the last quantifiable concentration, Clast is the predicted serum concentration at the last quantifiable time point estimated from the log linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where AUCinf was determined.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA ng*hr/mL | — |
| PF-06840003 125 MG QD | Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA ng*hr/mL | — |
| PF-06840003 250 MG QD | Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 5549 ng*hr/mL | Geometric Coefficient of Variation 85 |
| PF-06840003 250 MG QD | Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 9174 ng*hr/mL | Geometric Coefficient of Variation 69 |
| PF-06840003 500 MG BID | Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 5343 ng*hr/mL | Geometric Coefficient of Variation 40 |
| PF-06840003 500 MG BID | Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 8645 ng*hr/mL | Geometric Coefficient of Variation 39 |
Secondary
Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1]
AUClast of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA nanogram*hour per milliliter (ng*hr/mL) | — |
| PF-06840003 125 MG QD | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA nanogram*hour per milliliter (ng*hr/mL) | — |
| PF-06840003 250 MG QD | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 7626 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| PF-06840003 250 MG QD | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 4517 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 80 |
| PF-06840003 250 MG BID | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 13340 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| PF-06840003 250 MG BID | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 21670 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| PF-06840003 500 MG BID | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 17720 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 78 |
| PF-06840003 500 MG BID | Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 28250 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 71 |
Secondary
Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1]
Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA nanograms per milliliter (ng/mL) | — |
| PF-06840003 125 MG QD | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA nanograms per milliliter (ng/mL) | — |
| PF-06840003 250 MG QD | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1309 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| PF-06840003 250 MG QD | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 775.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| PF-06840003 250 MG BID | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1135 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 6 |
| PF-06840003 250 MG BID | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1763 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 8 |
| PF-06840003 500 MG BID | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1407 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| PF-06840003 500 MG BID | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2286 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
Secondary
Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1]
t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where t1/2 was determined.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | NA hr | — |
| PF-06840003 125 MG QD | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | NA hr | — |
| PF-06840003 250 MG QD | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 3.773 hr | Standard Deviation 1.5931 |
| PF-06840003 250 MG QD | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 3.580 hr | Standard Deviation 1.5943 |
| PF-06840003 500 MG BID | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 2.090 hr | Standard Deviation 0.45033 |
| PF-06840003 500 MG BID | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 1.943 hr | Standard Deviation 0.39273 |
Secondary
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1]
Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.
Time frame: Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose
Population: The analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-06840003 125 MG QD | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.58 hour (hr) |
| PF-06840003 125 MG QD | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.50 hour (hr) |
| PF-06840003 250 MG QD | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.05 hour (hr) |
| PF-06840003 250 MG QD | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.51 hour (hr) |
| PF-06840003 250 MG BID | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 1.95 hour (hr) |
| PF-06840003 250 MG BID | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 2.05 hour (hr) |
| PF-06840003 500 MG BID | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840002 | 3.02 hour (hr) |
| PF-06840003 500 MG BID | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] | PF-06840001 | 3.98 hour (hr) |
Secondary
Steady-State Trough Level Ratio [Part 1]
Steady-State trough level ratio was determined by cerebrospinal fluid (CSF)/Plasma. CSF/Plasma ratio was calculated based on the unbound concentration of each analyte. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.
Time frame: Baseline and Day 15
Population: The Overall Number of Participants Analyzed represents the total number of participants in the treatment group in the indicated population. The Number Analyzed represents the number of participants contributing to the summary statistics, i.e. number of participants where CSF/Plasma ratio was determined.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06840003 250 MG BID | Steady-State Trough Level Ratio [Part 1] | PF-06840002 | 1.00 ratio | Standard Deviation 0.007 |
| PF-06840003 250 MG BID | Steady-State Trough Level Ratio [Part 1] | PF-06840001 | 0.89 ratio | Standard Deviation 0.105 |
| PF-06840003 500 MG BID | Steady-State Trough Level Ratio [Part 1] | PF-06840002 | 1.00 ratio | Standard Deviation 0.692 |
| PF-06840003 500 MG BID | Steady-State Trough Level Ratio [Part 1] | PF-06840001 | 0.88 ratio | Standard Deviation 0.619 |