First in Patient Study for PF-06840003 in Malignant Gliomas
Study Details
Study Description
Brief Summary
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: PF-06840003 Daily Oral PF-06840003 |
Drug: PF-06840003
Daily Oral PF-06840003
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Ronald Reagan UCLA Medical Center | Los Angeles | California | United States | 90095-6894 |
2 | UCLA Clinical & Translational Research Center | Los Angeles | California | United States | 90095 |
3 | UCLA Oncology Center | Los Angeles | California | United States | 90095 |
4 | UCLA School of Medicine | Los Angeles | California | United States | 90095 |
5 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
6 | Brigham & Women's Hospital | Boston | Massachusetts | United States | 02115 |
7 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
8 | University of New Mexico Comprehensive Cancer Center | Albuquerque | New Mexico | United States | 87102 |
9 | Columbia University Medical Center | New York | New York | United States | 10019 |
10 | Columbia University Medical Center | New York | New York | United States | 10032 |
11 | CUMC Research Pharmacy | New York | New York | United States | 10032 |
12 | Columbia Doctors Tarrytown | Tarrytown | New York | United States | 10591 |
13 | Duke Cancer Center | Durham | North Carolina | United States | 27710 |
14 | Duke University Medical Center, Duke Cancer Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- C0591001
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Period Title: Overall Study | ||||
STARTED | 2 | 4 | 3 | 8 |
COMPLETED | 2 | 4 | 3 | 5 |
NOT COMPLETED | 0 | 0 | 0 | 3 |
Baseline Characteristics
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID | Total |
---|---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. | Total of all reporting groups |
Overall Participants | 2 | 4 | 3 | 8 | 17 |
Age (years) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [years] |
44.5
(19.1)
|
51.8
(14.5)
|
49.3
(12.1)
|
58.1
(14.6)
|
53.5
(14.1)
|
Age, Customized (Count of Participants) | |||||
18-44 Years |
1
50%
|
2
50%
|
1
33.3%
|
1
12.5%
|
5
29.4%
|
45-64 Years |
1
50%
|
1
25%
|
2
66.7%
|
3
37.5%
|
7
41.2%
|
>=65 Years |
0
0%
|
1
25%
|
0
0%
|
4
50%
|
5
29.4%
|
Sex: Female, Male (Count of Participants) | |||||
Female |
1
50%
|
0
0%
|
1
33.3%
|
3
37.5%
|
5
29.4%
|
Male |
1
50%
|
4
100%
|
2
66.7%
|
5
62.5%
|
12
70.6%
|
Race/Ethnicity, Customized (Count of Participants) | |||||
White |
2
100%
|
4
100%
|
3
100%
|
7
87.5%
|
16
94.1%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
5.9%
|
Outcome Measures
Title | Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All Part 1 enrolled participants who received at least 1 dose of study treatment. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All Part 1 enrolled participants who received at least 1 dose of study treatment. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
All-causality TEAEs |
2
100%
|
4
100%
|
3
100%
|
8
100%
|
Treatment-related TEAEs |
1
50%
|
4
100%
|
2
66.7%
|
7
87.5%
|
Title | 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] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All Part 1 enrolled participants who received at least 1 dose of study treatment. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Grade 3 or 4 |
0
0%
|
1
25%
|
1
33.3%
|
2
25%
|
Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Objective Response Rate (ORR) [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population included all the participants enrolled. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Week 8 |
0.00
0%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
Week 16 |
0.00
0%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
Week 24 |
0.00
0%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
Title | Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population included all the participants enrolled. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Week 8 |
50.0
2500%
|
50.0
1250%
|
33.3
1110%
|
25.0
312.5%
|
Week 16 |
50.0
2500%
|
0.0
0%
|
66.7
2223.3%
|
25.0
312.5%
|
Week 24 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
25.0
312.5%
|
Title | 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] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All Part 1 enrolled participants who received at least 1 dose of study treatment. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Anemia, Grade 0 |
1
50%
|
2
50%
|
0
0%
|
2
25%
|
Anemia, Grade 1 |
0
0%
|
2
50%
|
3
100%
|
6
75%
|
Anemia, Grade 2 |
1
50%
|
0
0%
|
0
0%
|
0
0%
|
Hemoglobin increased, Grade 0 |
2
100%
|
4
100%
|
3
100%
|
8
100%
|
Lymphocyte count increased, Grade 0 |
2
100%
|
4
100%
|
3
100%
|
8
100%
|
Lymphopenia, Grade 0 |
1
50%
|
2
50%
|
1
33.3%
|
5
62.5%
|
Lymphopenia, Grade 1 |
1
50%
|
1
25%
|
0
0%
|
1
12.5%
|
Lymphopenia, Grade 2 |
0
0%
|
1
25%
|
1
33.3%
|
0
0%
|
Lymphopenia, Grade 3 |
0
0%
|
0
0%
|
1
33.3%
|
2
25%
|
Neutrophils (absolute), Grade 0 |
1
50%
|
3
75%
|
2
66.7%
|
7
87.5%
|
Neutrophils (absolute), Grade 1 |
1
50%
|
1
25%
|
0
0%
|
1
12.5%
|
Neutrophils (absolute), Grade 2 |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
Platelets, Grade 0 |
2
100%
|
2
50%
|
3
100%
|
5
62.5%
|
Platelets, Grade 1 |
0
0%
|
2
50%
|
0
0%
|
3
37.5%
|
WBC, Grade 0 |
2
100%
|
3
75%
|
1
33.3%
|
6
75%
|
WBC, Grade 1 |
0
0%
|
1
25%
|
1
33.3%
|
1
12.5%
|
WBC, Grade 2 |
0
0%
|
0
0%
|
1
33.3%
|
1
12.5%
|
Title | 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] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All Part 1 enrolled participants who received at least 1 dose of study treatment. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
ALT, Grade 0 |
2
100%
|
2
50%
|
3
100%
|
7
87.5%
|
ALT, Grade 1 |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
ALT, Grade 3 |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
ALT, Grade 4 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Alkaline phosphatase, Grade 0 |
2
100%
|
3
75%
|
3
100%
|
6
75%
|
Alkaline phosphatase, Grade 1 |
0
0%
|
1
25%
|
0
0%
|
2
25%
|
AST, Grade 0 |
2
100%
|
3
75%
|
3
100%
|
7
87.5%
|
AST, Grade 2 |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
AST, Grade 4 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Bilirubin (total), Grade 0 |
2
100%
|
4
100%
|
3
100%
|
8
100%
|
Creatinine, Grade 0 |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
Creatinine, Grade 1 |
2
100%
|
4
100%
|
2
66.7%
|
7
87.5%
|
Creatinine, Grade 2 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hypercalcemia, Grade 0 |
1
50%
|
4
100%
|
3
100%
|
8
100%
|
Hypercalcemia, Grade 1 |
1
50%
|
0
0%
|
0
0%
|
0
0%
|
Hyperglycemia, Grade 0 |
1
50%
|
0
0%
|
3
100%
|
1
12.5%
|
Hyperglycemia, Grade 1 |
1
50%
|
4
100%
|
0
0%
|
4
50%
|
Hyperglycemia, Grade 2 |
0
0%
|
0
0%
|
0
0%
|
2
25%
|
Hyperglycemia, Grade 3 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hyperkalemia, Grade 0 |
2
100%
|
4
100%
|
3
100%
|
7
87.5%
|
Hyperkalemia, Grade 3 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hypermagnesemia, Grade 0 |
2
100%
|
4
100%
|
3
100%
|
7
87.5%
|
Hypermagnesemia, Grade 1 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hypernatremia, Grade 0 |
2
100%
|
4
100%
|
3
100%
|
7
87.5%
|
Hypernatremia, Grade 1 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hypoalbuminemia, Grade 0 |
2
100%
|
3
75%
|
3
100%
|
5
62.5%
|
Hypoalbuminemia, Grade 1 |
0
0%
|
1
25%
|
0
0%
|
2
25%
|
Hypoalbuminemia, Grade 2 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hypocalcemia, Grade 0 |
2
100%
|
3
75%
|
0
0%
|
6
75%
|
Hypocalcemia, Grade 1 |
0
0%
|
1
25%
|
3
100%
|
1
12.5%
|
Hypocalcemia, Grade 2 |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
Hypoglycemia, Grade 0 |
2
100%
|
3
75%
|
3
100%
|
8
100%
|
Hypoglycemia, Grade 1 |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
Hypokalemia, Grade 0 |
2
100%
|
4
100%
|
1
33.3%
|
4
50%
|
Hypokalemia, Grade 1 |
0
0%
|
0
0%
|
2
66.7%
|
4
50%
|
Hypomagnesemia, Grade 0 |
2
100%
|
4
100%
|
2
66.7%
|
8
100%
|
Hypomagnesemia, Grade 1 |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
Hyponatremia, Grade 0 |
2
100%
|
4
100%
|
1
33.3%
|
7
87.5%
|
Hyponatremia, Grade 1 |
0
0%
|
0
0%
|
1
33.3%
|
1
12.5%
|
Hyponatremia, Grade 3 |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
Hypophosphatemia, Grade 0 |
2
100%
|
4
100%
|
3
100%
|
6
75%
|
Hypophosphatemia, Grade 2 |
0
0%
|
0
0%
|
0
0%
|
2
25%
|
Title | Number of Participants With Clinically Significant Findings in Vital Signs [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All Part 1 enrolled participants who received at least 1 dose of study treatment. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
775.0
(37)
|
1135
(6)
|
1407
(23)
|
PF-06840001 |
NA
(NA)
|
1309
(28)
|
1763
(8)
|
2286
(20)
|
Title | Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
1.58
|
1.51
|
1.95
|
3.02
|
PF-06840001 |
2.50
|
2.05
|
2.05
|
3.98
|
Title | 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] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
4517
(80)
|
13340
(21)
|
17720
(78)
|
PF-06840001 |
NA
(NA)
|
7626
(66)
|
21670
(24)
|
28250
(71)
|
Title | Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
5356
(60)
|
7606
(11)
|
8653
(57)
|
PF-06840001 |
NA
(NA)
|
8999
(49)
|
12280
(15)
|
13910
(52)
|
Title | Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
751.6
(85)
|
1561
(40)
|
|
PF-06840001 |
NA
(NA)
|
454.6
(69)
|
965.4
(39)
|
Title | Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
228.4
(27)
|
277.2
(20)
|
|
PF-06840001 |
NA
(NA)
|
129.3
(12)
|
159.6
(25)
|
Title | Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
3.773
(1.5931)
|
2.090
(0.45033)
|
|
PF-06840001 |
NA
(NA)
|
3.580
(1.5943)
|
1.943
(0.39273)
|
Title | 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] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
5549
(85)
|
5343
(40)
|
|
PF-06840001 |
NA
(NA)
|
9174
(69)
|
8645
(39)
|
Title | Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
779.3
(9)
|
1763
(25)
|
2474
(66)
|
PF-06840001 |
NA
(NA)
|
1334
(5)
|
2810
(24)
|
3978
(58)
|
Title | Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
3.00
|
3.03
|
2.00
|
3.02
|
PF-06840001 |
3.00
|
3.03
|
2.00
|
3.95
|
Title | Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
6680
(75)
|
12730
(50)
|
20410
(96)
|
PF-06840001 |
NA
(NA)
|
10440
(64)
|
21020
(50)
|
32080
(89)
|
Title | Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
5.58
|
2.90
|
2.68
|
2.885
|
PF-06840001 |
5.505
|
2.61
|
2.50
|
2.685
|
Title | Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
15.85
(21.622)
|
687.3
(409.76)
|
1611
(1749.7)
|
PF-06840001 |
NA
(NA)
|
21.75
(27.298)
|
1079
(587.86)
|
2308
(2161.3)
|
Title | Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
278
(75)
|
1060
(50)
|
1702
(96)
|
PF-06840001 |
NA
(NA)
|
435.1
(64)
|
1755
(49)
|
2673
(89)
|
Title | Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
624.2
(75)
|
327.6
(50)
|
408.3
(96)
|
PF-06840001 |
NA
(NA)
|
399.1
(64)
|
198.2
(50)
|
259.5
(89)
|
Title | Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
184.5
|
216
|
128
|
270.5
|
PF-06840001 |
102.6
|
117
|
72.6
|
162
|
Title | Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
1.244
(31)
|
1.670
(45)
|
2.359
(45)
|
PF-06840001 |
NA
(NA)
|
1.163
(31)
|
1.717
(45)
|
2.304
(41)
|
Title | Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
NA
(NA)
|
1.289
(37)
|
1.961
(72)
|
|
PF-06840001 |
NA
(NA)
|
1.266
(31)
|
1.895
(61)
|
Title | Steady-State Trough Level Ratio [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
PF-06840002 |
1.00
(0.007)
|
1.00
(0.692)
|
||
PF-06840001 |
0.89
(0.105)
|
0.88
(0.619)
|
Title | Plasma Kynurenine and Tryptophan [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the total number of participants in the treatment group in the indicated population. |
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Kynurenine |
1.545
(0.2051)
|
2.185
(1.7443)
|
1.144
(0.1479)
|
1.523
(0.4321)
|
Tryptophan |
48.15
(4.596)
|
29.55
(4.611)
|
36.77
(7.681)
|
33.10
(4.590)
|
Title | Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1] |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID |
---|---|---|---|---|
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. |
Measure Participants | 2 | 4 | 3 | 8 |
Mean (Standard Deviation) [ratio] |
38.467
(0.6791)
|
53.066
(24.9722)
|
25.854
(7.6209)
|
42.463
(NA)
|
Adverse Events
Time Frame | Baseline up to 1 year | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | The same event may appear as both an AE and an SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs. | |||||||
Arm/Group Title | PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID | ||||
Arm/Group Description | PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles. | PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. | ||||
All Cause Mortality |
||||||||
PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/8 (0%) | ||||
Serious Adverse Events |
||||||||
PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 3/8 (37.5%) | ||||
Infections and infestations | ||||||||
Lung infection | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Investigations | ||||||||
Alanine aminotransferase increased | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Aspartate aminotransferase increased | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Glioblastoma multiforme | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Nervous system disorders | ||||||||
Encephalopathy | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Generalised tonic-clonic seizure | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Headache | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Hemiparesis | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
PF-06840003 125 MG QD | PF-06840003 250 MG QD | PF-06840003 250 MG BID | PF-06840003 500 MG BID | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/2 (100%) | 4/4 (100%) | 3/3 (100%) | 8/8 (100%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 1/2 (50%) | 2/4 (50%) | 3/3 (100%) | 3/8 (37.5%) | ||||
Cardiac disorders | ||||||||
Bradycardia | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Left ventricular dysfunction | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Ear and labyrinth disorders | ||||||||
Ear pain | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Tinnitus | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Vertigo | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Gastrointestinal disorders | ||||||||
Anal incontinence | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Constipation | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/8 (0%) | ||||
Diarrhoea | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Gastrooesophageal reflux disease | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Nausea | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Vomiting | 1/2 (50%) | 1/4 (25%) | 1/3 (33.3%) | 1/8 (12.5%) | ||||
General disorders | ||||||||
Fatigue | 1/2 (50%) | 3/4 (75%) | 1/3 (33.3%) | 4/8 (50%) | ||||
Influenza like illness | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Non-cardiac chest pain | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Oedema | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Oedema peripheral | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Pyrexia | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Infections and infestations | ||||||||
Fungal skin infection | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Lung infection | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Upper respiratory tract infection | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Urinary tract infection | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Injury, poisoning and procedural complications | ||||||||
Fall | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 1/8 (12.5%) | ||||
Investigations | ||||||||
Alanine aminotransferase increased | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Aspartate aminotransferase increased | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Blood alkaline phosphatase increased | 0/2 (0%) | 2/4 (50%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Blood bilirubin increased | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Blood creatinine increased | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Ejection fraction decreased | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Lymphocyte count decreased | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 1/8 (12.5%) | ||||
Neutrophil count decreased | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 1/8 (12.5%) | ||||
Platelet count decreased | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Protein total increased | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Weight decreased | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
White blood cell count decreased | 0/2 (0%) | 1/4 (25%) | 2/3 (66.7%) | 1/8 (12.5%) | ||||
Metabolism and nutrition disorders | ||||||||
Decreased appetite | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Hyperglycaemia | 0/2 (0%) | 3/4 (75%) | 0/3 (0%) | 2/8 (25%) | ||||
Hypocalcaemia | 0/2 (0%) | 0/4 (0%) | 3/3 (100%) | 1/8 (12.5%) | ||||
Hypokalaemia | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 3/8 (37.5%) | ||||
Hypomagnesaemia | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Hyponatraemia | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 1/8 (12.5%) | ||||
Hypophosphataemia | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Arthralgia | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | ||||
Muscular weakness | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Myalgia | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Neck pain | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Pain in extremity | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Temporomandibular joint syndrome | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Glioblastoma multiforme | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Haemangioma of skin | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Nervous system disorders | ||||||||
Amnesia | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Aphasia | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 4/8 (50%) | ||||
Apraxia | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/8 (0%) | ||||
Ataxia | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Brain oedema | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Disturbance in attention | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Dizziness | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Dysarthria | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 2/8 (25%) | ||||
Facial paralysis | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/8 (0%) | ||||
Facial paresis | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Headache | 0/2 (0%) | 2/4 (50%) | 1/3 (33.3%) | 2/8 (25%) | ||||
Hemianopia homonymous | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Hemiparesis | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Memory impairment | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Nystagmus | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Paraesthesia | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Partial seizures | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/8 (0%) | ||||
Peripheral sensory neuropathy | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Peroneal nerve palsy | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Pyramidal tract syndrome | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 1/8 (12.5%) | ||||
Seizure | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | ||||
Somnolence | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Tremor | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | ||||
Visual field defect | 1/2 (50%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Psychiatric disorders | ||||||||
Agitation | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Confusional state | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 2/8 (25%) | ||||
Depression | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Dysphoria | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Insomnia | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Personality change | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Renal and urinary disorders | ||||||||
Chromaturia | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Micturition urgency | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Polyuria | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Proteinuria | 1/2 (50%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Urinary incontinence | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | ||||
Respiratory, thoracic and mediastinal disorders | ||||||||
Nasal congestion | 1/2 (50%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Oropharyngeal pain | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Productive cough | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/8 (0%) | ||||
Rhinitis allergic | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Sneezing | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) | ||||
Skin and subcutaneous tissue disorders | ||||||||
Acne | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Alopecia | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Dry skin | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/8 (0%) | ||||
Rash | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Vascular disorders | ||||||||
Hypertension | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/8 (12.5%) | ||||
Hypotension | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/8 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title | Pfizer ClinicalTrials.gov Call Center |
---|---|
Organization | Pfizer, Inc. |
Phone | 1-800-718-1021 |
ClinicalTrials.gov_Inquiries@pfizer.com |
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