Trial Outcomes & Findings for First in Patient Study for PF-06840003 in Malignant Gliomas (NCT NCT02764151)

Last Updated: 2020-01-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

Baseline to Day 28

Results posted on

2020-01-27

Participant Flow

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.

Participant milestones

Participant milestones
Measure	PF-06840003 125 MG QD PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Overall Study STARTED	2	4	3	8
Overall Study COMPLETED	2	4	3	5
Overall Study NOT COMPLETED	0	0	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-06840003 125 MG QD PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Overall Study Subject refused further follow-up	0	0	0	1
Overall Study Other	0	0	0	2

Baseline Characteristics

First in Patient Study for PF-06840003 in Malignant Gliomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.	Total n=17 Participants Total of all reporting groups
Age, Continuous	44.5 years STANDARD_DEVIATION 19.1 • n=5 Participants	51.8 years STANDARD_DEVIATION 14.5 • n=7 Participants	49.3 years STANDARD_DEVIATION 12.1 • n=5 Participants	58.1 years STANDARD_DEVIATION 14.6 • n=4 Participants	53.5 years STANDARD_DEVIATION 14.1 • n=21 Participants
Age, Customized 18-44 Years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Age, Customized 45-64 Years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants
Age, Customized >=65 Years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	5 Participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	12 Participants n=21 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants	16 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Day 28

Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline up to 1 year

Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] All-causality TEAEs	2 Participants	4 Participants	3 Participants	8 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1] Treatment-related TEAEs	1 Participants	4 Participants	2 Participants	7 Participants

PRIMARY outcome

Timeframe: Baseline up to 1 year

Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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	1 Participants	1 Participants	2 Participants
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	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 8, 16, and 24

Population: The analysis population included all the participants enrolled.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Objective Response Rate (ORR) [Part 1] Week 8	0.00 Percentage of Participants Interval 0.0 to 84.19	0.00 Percentage of Participants Interval 0.0 to 60.24	0.00 Percentage of Participants Interval 0.0 to 70.76	0.00 Percentage of Participants Interval 0.0 to 36.94
Objective Response Rate (ORR) [Part 1] Week 16	0.00 Percentage of Participants Interval 0.0 to 84.19	0.00 Percentage of Participants Interval 0.0 to 60.24	0.00 Percentage of Participants Interval 0.0 to 70.76	0.00 Percentage of Participants Interval 0.0 to 36.94
Objective Response Rate (ORR) [Part 1] Week 24	0.00 Percentage of Participants Interval 0.0 to 84.19	0.00 Percentage of Participants Interval 0.0 to 60.24	0.00 Percentage of Participants Interval 0.0 to 70.76	0.00 Percentage of Participants Interval 0.0 to 36.94

SECONDARY outcome

Timeframe: Weeks 8, 16, and 24

Population: The analysis population included all the participants enrolled.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] Week 8	50.0 percentage of participants Interval 1.26 to 98.74	50.0 percentage of participants Interval 6.76 to 93.24	33.3 percentage of participants Interval 0.84 to 90.57	25.0 percentage of participants Interval 3.19 to 65.09
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] Week 16	50.0 percentage of participants Interval 1.26 to 98.74	0.0 percentage of participants Interval 0.0 to 60.24	66.7 percentage of participants Interval 9.43 to 99.16	25.0 percentage of participants Interval 3.19 to 65.09
Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1] Week 24	0.0 percentage of participants Interval 0.0 to 84.19	0.0 percentage of participants Interval 0.0 to 60.24	0.0 percentage of participants Interval 0.0 to 70.76	25.0 percentage of participants Interval 3.19 to 65.09

SECONDARY outcome

Timeframe: Baseline up to 1 year

Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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	4 Participants	3 Participants	8 Participants
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	1 Participants	1 Participants	0 Participants
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	0 Participants	1 Participants	2 Participants
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	2 Participants	1 Participants	5 Participants
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	3 Participants	2 Participants	7 Participants
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	1 Participants	0 Participants	1 Participants
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	0 Participants	1 Participants	0 Participants
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	1 Participants	0 Participants	1 Participants
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	2 Participants	3 Participants	5 Participants
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	1 Participants	1 Participants	1 Participants
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	0 Participants	1 Participants	1 Participants
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	2 Participants	0 Participants	3 Participants
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	3 Participants	1 Participants	6 Participants
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	2 Participants	3 Participants	6 Participants
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	0 Participants	0 Participants	0 Participants
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	4 Participants	3 Participants	8 Participants
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	2 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to 1 year

Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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	2 Participants	3 Participants	7 Participants
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	1 Participants	0 Participants	0 Participants
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	1 Participants	0 Participants	0 Participants
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	0 Participants	0 Participants	1 Participants
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	0 Participants	1 Participants	0 Participants
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	3 Participants	3 Participants	6 Participants
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	1 Participants	0 Participants	2 Participants
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	3 Participants	3 Participants	7 Participants
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	1 Participants	0 Participants	0 Participants
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	0 Participants	0 Participants	1 Participants
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	4 Participants	3 Participants	8 Participants
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	4 Participants	2 Participants	7 Participants
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	0 Participants	0 Participants	1 Participants
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	4 Participants	3 Participants	8 Participants
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	0 Participants	0 Participants	0 Participants
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	0 Participants	3 Participants	1 Participants
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	4 Participants	0 Participants	4 Participants
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	0 Participants	0 Participants	2 Participants
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	0 Participants	0 Participants	1 Participants
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	4 Participants	3 Participants	7 Participants
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	0 Participants	0 Participants	1 Participants
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	4 Participants	3 Participants	7 Participants
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	0 Participants	0 Participants	1 Participants
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	4 Participants	3 Participants	7 Participants
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	0 Participants	0 Participants	1 Participants
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	3 Participants	3 Participants	5 Participants
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	1 Participants	0 Participants	2 Participants
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	0 Participants	0 Participants	1 Participants
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	3 Participants	0 Participants	6 Participants
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	1 Participants	3 Participants	1 Participants
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	0 Participants	0 Participants	1 Participants
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	3 Participants	3 Participants	8 Participants
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	1 Participants	0 Participants	0 Participants
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	4 Participants	1 Participants	4 Participants
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	0 Participants	2 Participants	4 Participants
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	4 Participants	2 Participants	8 Participants
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	0 Participants	1 Participants	0 Participants
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	4 Participants	1 Participants	7 Participants
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	0 Participants	1 Participants	1 Participants
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	0 Participants	1 Participants	0 Participants
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	4 Participants	3 Participants	6 Participants
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	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to 1 year

Population: All Part 1 enrolled participants who received at least 1 dose of study treatment.

Vital signs included measurements of blood pressure and temperature (oral, tympanic, temporal or axillary). The investigator judged any clinically significant vital signs findings.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Number of Participants With Clinically Significant Findings in Vital Signs [Part 1]	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 580.5 (468-693).	775.0 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 37	1135 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 6	1407 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23
Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 991.0 (792-1190).	1309 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 28	1763 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 8	2286 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 20

SECONDARY outcome

Timeframe: 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.

Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	1.58 hour (hr) Interval 1.0 to 2.15	1.51 hour (hr) Interval 1.0 to 2.08	1.95 hour (hr) Interval 1.0 to 2.05	3.02 hour (hr) Interval 1.0 to 4.05
Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	2.50 hour (hr) Interval 1.0 to 4.0	2.05 hour (hr) Interval 1.0 to 2.13	2.05 hour (hr) Interval 1.95 to 4.0	3.98 hour (hr) Interval 1.0 to 4.05

SECONDARY outcome

Timeframe: 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.

AUClast of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 6250 (5790-6710).	7626 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 66	21670 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 24	28250 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 71
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 3155 (2450-3860).	4517 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 80	13340 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 21	17720 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 78

SECONDARY outcome

Timeframe: 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.

AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 3380 (2900-3860).	5356 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 60	7606 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 11	8653 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 57
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 6250 (5790-6710).	8999 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 49	12280 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 15	13910 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 52

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA Milliliter per minute (mL/min) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The CL/F of this 1 participant is 527.0 mL/min.	751.6 Milliliter per minute (mL/min) Geometric Coefficient of Variation 85	—	1561 Milliliter per minute (mL/min) Geometric Coefficient of Variation 40
Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA Milliliter per minute (mL/min) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The CL/F of this 1 participant is 358.0 mL/min.	454.6 Milliliter per minute (mL/min) Geometric Coefficient of Variation 69	—	965.4 Milliliter per minute (mL/min) Geometric Coefficient of Variation 39

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA Liter Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The Vz/F of this 1 participant is 186.0L.	228.4 Liter Geometric Coefficient of Variation 27	—	277.2 Liter Geometric Coefficient of Variation 20
Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA Liter Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The Vz/F of this 1 participant is 97.70L.	129.3 Liter Geometric Coefficient of Variation 12	—	159.6 Liter Geometric Coefficient of Variation 25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA hr Standard Deviation NA It is not possible to calculate mean (standard deviation) for insufficient number of participants (n=1), so NA is listed. The t1/2 of this 1 participant is 4.080 hr.	3.773 hr Standard Deviation 1.5931	—	2.090 hr Standard Deviation 0.45033
Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA hr Standard Deviation NA It is not possible to calculate mean (standard deviation) for insufficient number of participants (n=1), so NA is listed. The t1/2 of this 1 participant is 3.150 hr.	3.580 hr Standard Deviation 1.5943	—	1.943 hr Standard Deviation 0.39273

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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 nghr/mL Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The AUCinf of this 1 participant is 3960 ng\hr/mL.	5549 ng*hr/mL Geometric Coefficient of Variation 85	—	5343 ng*hr/mL Geometric Coefficient of Variation 40
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 nghr/mL Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The AUCinf of this 1 participant is 5820 ng\hr/mL.	9174 ng*hr/mL Geometric Coefficient of Variation 69	—	8645 ng*hr/mL Geometric Coefficient of Variation 39

SECONDARY outcome

Timeframe: 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.

Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA ng/mL Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 623.0 (463-783).	779.3 ng/mL Geometric Coefficient of Variation 9	1763 ng/mL Geometric Coefficient of Variation 25	2474 ng/mL Geometric Coefficient of Variation 66
Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA ng/mL Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 580.5 (468-693).	1334 ng/mL Geometric Coefficient of Variation 5	2810 ng/mL Geometric Coefficient of Variation 24	3978 ng/mL Geometric Coefficient of Variation 58

SECONDARY outcome

Timeframe: 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.

Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	3.00 hr Interval 2.0 to 4.0	3.03 hr Interval 2.08 to 4.07	2.00 hr Interval 2.0 to 2.1	3.02 hr Interval 1.0 to 4.0
Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	3.00 hr Interval 2.0 to 4.0	3.03 hr Interval 2.08 to 4.07	2.00 hr Interval 2.0 to 2.1	3.95 hr Interval 2.08 to 8.0

SECONDARY outcome

Timeframe: 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.

AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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 Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 6115 (3320-8910).	6680 ng*hr/mL Geometric Coefficient of Variation 75	12730 ng*hr/mL Geometric Coefficient of Variation 50	20410 ng*hr/mL Geometric Coefficient of Variation 96
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 Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 10780 (5950-15600).	10440 ng*hr/mL Geometric Coefficient of Variation 64	21020 ng*hr/mL Geometric Coefficient of Variation 50	32080 ng*hr/mL Geometric Coefficient of Variation 89

SECONDARY outcome

Timeframe: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	5.58 hr Interval 4.22 to 6.94	2.90 hr Interval 2.16 to 3.64	2.68 hr Interval 2.68 to 2.68	2.885 hr Interval 1.97 to 3.8
Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	5.505 hr Interval 4.16 to 6.85	2.61 hr Interval 1.92 to 3.63	2.50 hr Interval 2.5 to 2.5	2.685 hr Interval 1.91 to 3.46

SECONDARY outcome

Timeframe: 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.

Cmin of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA ng/mL Standard Deviation NA It is not possible and meaningful to calculate mean (standard deviation) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 63.95 (11.9-116).	15.85 ng/mL Standard Deviation 21.622	687.3 ng/mL Standard Deviation 409.76	1611 ng/mL Standard Deviation 1749.7
Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA ng/mL Standard Deviation NA It is not possible and meaningful to calculate mean (standard deviation) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 109.5 (20.9-198).	21.75 ng/mL Standard Deviation 27.298	1079 ng/mL Standard Deviation 587.86	2308 ng/mL Standard Deviation 2161.3

SECONDARY outcome

Timeframe: 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.

Cav of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA ng/mL Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 254.5 (138-371).	278 ng/mL Geometric Coefficient of Variation 75	1060 ng/mL Geometric Coefficient of Variation 50	1702 ng/mL Geometric Coefficient of Variation 96
Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA ng/mL Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 449.5 (248-651).	435.1 ng/mL Geometric Coefficient of Variation 64	1755 ng/mL Geometric Coefficient of Variation 49	2673 ng/mL Geometric Coefficient of Variation 89

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA mL/min Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 431.0 (234-628).	624.2 mL/min Geometric Coefficient of Variation 75	327.6 mL/min Geometric Coefficient of Variation 50	408.3 mL/min Geometric Coefficient of Variation 96
Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA mL/min Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 241.5 (133-350).	399.1 mL/min Geometric Coefficient of Variation 64	198.2 mL/min Geometric Coefficient of Variation 50	259.5 mL/min Geometric Coefficient of Variation 89

SECONDARY outcome

Timeframe: Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	184.5 Liter Interval 140.0 to 229.0	216 Liter Interval 202.0 to 230.0	128 Liter Interval 128.0 to 128.0	270.5 Liter Interval 269.0 to 272.0
Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	102.6 Liter Interval 79.1 to 126.0	117 Liter Interval 114.0 to 125.0	72.6 Liter Interval 72.6 to 72.6	162 Liter Interval 153.0 to 171.0

SECONDARY outcome

Timeframe: 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.

Rac of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCtau (single dose).

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA ratio Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 1.725 (1.14-2.31).	1.244 ratio Geometric Coefficient of Variation 31	1.670 ratio Geometric Coefficient of Variation 45	2.359 ratio Geometric Coefficient of Variation 45
Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA ratio Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 1.680 (1.03-2.33).	1.163 ratio Geometric Coefficient of Variation 31	1.717 ratio Geometric Coefficient of Variation 45	2.304 ratio Geometric Coefficient of Variation 41

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] PF-06840002	NA ratio Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The Rss of this 1 participant is 2.250.	1.289 ratio Geometric Coefficient of Variation 37	—	1.961 ratio Geometric Coefficient of Variation 72
Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1] PF-06840001	NA ratio Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=1), so NA is listed. The Rss of this 1 participant is 1.020.	1.266 ratio Geometric Coefficient of Variation 31	—	1.895 ratio Geometric Coefficient of Variation 61

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Steady-State Trough Level Ratio [Part 1] PF-06840002	—	—	1.00 ratio Standard Deviation 0.007	1.00 ratio Standard Deviation 0.692
Steady-State Trough Level Ratio [Part 1] PF-06840001	—	—	0.89 ratio Standard Deviation 0.105	0.88 ratio Standard Deviation 0.619

SECONDARY outcome

Timeframe: 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.

The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Plasma Kynurenine and Tryptophan [Part 1] Tryptophan	48.15 micromolar Standard Deviation 4.596	29.55 micromolar Standard Deviation 4.611	36.77 micromolar Standard Deviation 7.681	33.10 micromolar Standard Deviation 4.590
Plasma Kynurenine and Tryptophan [Part 1] Kynurenine	1.545 micromolar Standard Deviation 0.2051	2.185 micromolar Standard Deviation 1.7443	1.144 micromolar Standard Deviation 0.1479	1.523 micromolar Standard Deviation 0.4321

SECONDARY outcome

Timeframe: 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.

The Kynurenine/Tryptophan ratio was determined by 1000\*Kynurenine/Tryptophan.

Outcome measures

Outcome measures
Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1]	38.467 ratio Standard Deviation 0.6791	53.066 ratio Standard Deviation 24.9722	25.854 ratio Standard Deviation 7.6209	42.463 ratio Standard Deviation NA The number of participants in the group "PF-06840003 500 MG BID" on Cycle 1 Day 1 was 8 but the number of participants analyzed at the end of treatment was n=1. It is not possible to calculate standard deviation for n=1, therefore NA was listed.

Adverse Events

PF-06840003 125 MG QD

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

PF-06840003 250 MG QD

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

PF-06840003 250 MG BID

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PF-06840003 500 MG BID

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-06840003 125 MG QD n=2 participants at risk PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 participants at risk PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 participants at risk PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 participants at risk PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
Infections and infestations Lung infection	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.
Investigations Alanine aminotransferase increased	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.
Investigations Aspartate aminotransferase increased	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma multiforme	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.
Nervous system disorders Encephalopathy	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.
Nervous system disorders Headache	0.00% 0/2 • Baseline up to 1 year 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.	25.0% 1/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	0.00% 0/8 • Baseline up to 1 year 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.
Nervous system disorders Hemiparesis	0.00% 0/2 • Baseline up to 1 year 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.	0.00% 0/4 • Baseline up to 1 year 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.	0.00% 0/3 • Baseline up to 1 year 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.	12.5% 1/8 • Baseline up to 1 year 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.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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Restriction type: OTHER

Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 6250 (5790-6710).	7626 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 66	21670 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 24	28250 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 71
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 3155 (2450-3860).	4517 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 80	13340 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 21	17720 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 78

Measure	PF-06840003 125 MG QD n=2 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.	PF-06840003 250 MG QD n=4 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.	PF-06840003 250 MG BID n=3 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.	PF-06840003 500 MG BID n=8 Participants PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 3380 (2900-3860).	5356 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 60	7606 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 11	8653 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 57
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 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation NA It is not possible and meaningful to calculate geometric mean (geometric CV) for insufficient number of participants (n=2), so NA is listed. The median (range) was presented for n=2: 6250 (5790-6710).	8999 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 49	12280 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 15	13910 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 52