Trial Outcomes & Findings for First-In-Human Study Of Single And Multiple Ascending Doses Of PF-06751979 (NCT NCT02509117)

Results Overview

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 47 days in Part A, 29 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

55 participants

Primary outcome timeframe

Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days

Results posted on

2018-11-01

Participant Flow

Study conducted in 3 parts: Part A (4-period cross-over design), Part B and C (single period, parallel design).

Participant milestones

Participant milestones
Measure	Part A- PF-06751979: 3 mg, 12 mg, 40 mg, Placebo Participants received 3 milligram (mg) oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by placebo matched to PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by placebo matched to PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part A- PF-06751979: 3 mg, Placebo, PF-06751979: 40 mg, 160 mg Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by placebo matched to PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part A: Placebo, PF-06751979: 12 mg, 40 mg, 160 mg Participants received placebo matched to PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part B- Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Period 1-Part A:4 Days; Part B,C:19 Days STARTED	2	2	2	2	8	8	8	8	4	10
Period 1-Part A:4 Days; Part B,C:19 Days Treated	2	1	2	2	8	8	8	8	4	10
Period 1-Part A:4 Days; Part B,C:19 Days COMPLETED	2	1	2	2	8	8	8	8	4	8
Period 1-Part A:4 Days; Part B,C:19 Days NOT COMPLETED	0	1	0	0	0	0	0	0	0	2
Washout Period 1 (Part A: 7 Days) STARTED	2	1	2	2	0	0	0	0	0	0
Washout Period 1 (Part A: 7 Days) COMPLETED	2	1	2	2	0	0	0	0	0	0
Washout Period 1 (Part A: 7 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period 2 -Part A: 4 Days STARTED	2	2	2	2	0	0	0	0	0	0
Period 2 -Part A: 4 Days Treated	2	2	2	2	0	0	0	0	0	0
Period 2 -Part A: 4 Days COMPLETED	2	2	2	2	0	0	0	0	0	0
Period 2 -Part A: 4 Days NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Washout Period 2 (Part A: 7 Days) STARTED	2	2	2	2	0	0	0	0	0	0
Washout Period 2 (Part A: 7 Days) COMPLETED	2	2	2	2	0	0	0	0	0	0
Washout Period 2 (Part A: 7 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period 3 -Part A: 4 Days STARTED	2	2	2	2	0	0	0	0	0	0
Period 3 -Part A: 4 Days COMPLETED	2	2	2	2	0	0	0	0	0	0
Period 3 -Part A: 4 Days NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Washout Period 3 (Part A: 7 Days) STARTED	2	2	2	2	0	0	0	0	0	0
Washout Period 3 (Part A: 7 Days) COMPLETED	2	2	2	2	0	0	0	0	0	0
Washout Period 3 (Part A: 7 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period 4 -Part A: 4 Days STARTED	2	2	2	2	0	0	0	0	0	0
Period 4 -Part A: 4 Days COMPLETED	2	2	2	2	0	0	0	0	0	0
Period 4 -Part A: 4 Days NOT COMPLETED	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by placebo matched to PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Period 1-Part A:4 Days; Part B,C:19 Days Randomized, not treated	1	0
Period 1-Part A:4 Days; Part B,C:19 Days Investigator's Discretion	0	1
Period 1-Part A:4 Days; Part B,C:19 Days Withdrawal by Subject	0	1

Baseline Characteristics

First-In-Human Study Of Single And Multiple Ascending Doses Of PF-06751979

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A- PF-06751979: 3 mg, 12 mg, 40 mg, Placebo n=2 Participants Participants received 3 milligram (mg) oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by placebo matched to PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg n=3 Participants Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by placebo matched to PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part A- PF-06751979: 3 mg, Placebo, PF-06751979: 40 mg, 160 mg n=2 Participants Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by placebo matched to PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part A: Placebo, PF-06751979: 12 mg, 40 mg, 160 mg n=2 Participants Participants received placebo matched to PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period.	Part B- Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Total n=55 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	8 Participants n=21 Participants	8 Participants n=8 Participants	8 Participants n=8 Participants	8 Participants n=24 Participants	1 Participants n=42 Participants	1 Participants n=42 Participants	43 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	3 Participants n=42 Participants	9 Participants n=42 Participants	12 Participants n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	3 Participants n=42 Participants	6 Participants n=42 Participants	9 Participants n=42 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	8 Participants n=21 Participants	8 Participants n=8 Participants	8 Participants n=8 Participants	8 Participants n=24 Participants	1 Participants n=42 Participants	4 Participants n=42 Participants	46 Participants n=42 Participants

PRIMARY outcome

Timeframe: Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 47 days in Part A, 29 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=5 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=6 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=6 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=6 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	0 participants	1 participants	0 participants	0 participants	0 participants	1 participants	1 participants	2 participants	1 participants	3 participants	7 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Abnormality in physical examinations was based on investigator's discretion.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=5 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=6 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=6 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=6 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Number of Participants With Abnormal Physical Examinations Findings	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	3 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

The neurological examination included the assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait. Abnormality in neurological examinations was based on investigator's discretion.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=5 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=6 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=6 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=6 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Number of Participants With Abnormal Neurological Examinations Findings	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	0 participants	0 participants	0 participants	0 participants	2 participants

PRIMARY outcome

Timeframe: Baseline

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at baseline were reported.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=8 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=8 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=8 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=4 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=10 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 7

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at day 7 were reported.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=8 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=8 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=8 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=4 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=10 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 14

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 14 were reported.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=8 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=8 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=8 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=4 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=10 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 19

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 19 were reported.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=8 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=8 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=8 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=4 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=10 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Criteria for clinically significant ECG abnormalities: maximum PR interval \>=300 milliseconds (msec) and maximum PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 msec and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, maximum QRS interval \>=140 msec and a maximum IFB: Pctchg\>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to \<480 msec, 480 msec to \<500 msec or \>=500 msec and a maximum change of \<=30 change \<60 or \>=60 msec from baseline.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=5 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=6 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=6 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=6 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Abnormalities criteria:hematology(hemoglobin; hematocrit; RBC\<0.8\*lower limit of normal \[LLN\]; platelets\<0.5\*LLN,\>1.75\*upper limit of normal \[ULN\]; WBC\<0.6\*LLN,\>1.5\*ULN; lymphocytes; neutrophils; basophils; eosinophils; monocytes\<0.8\*LLN,\>1.2\*ULN; coagulation(prothrombin (PT); PT ratio\>1.1\*ULN), liver(bilirubin\>1.5\*ULN; aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; gamma GT\>0.3\*ULN; protein; albumin\<0.8\*LLN,\>1.2\*ULN); renal(blood urea nitrogen, creatinine\>1.3\*ULN; uric acid\>1.2\*ULN); electrolytes(sodium\<0.95\*LLN,\>1.05\*ULN; potassium; chloride; calcium; bicarbonate\<0.9\*LLN,\>1.1\*ULN), chemistry(glucose\<0.6\*LLN,\>1.5\* ULN); urinalysis(pH \<4.5,\>8; glucose, ketones, protein, blood, urobilinogen, nitrite, bilirubin, leukocyte, esterase\>1; WBC; bacteria\>=20, epithelial cells\>=6; granular casts, hyaline casts, red cell casts, white cell casts\>1; lipids(cholesterol\[C\], LDL-C\>1.3\*ULN; HDL-C\<0.8\*LLN, triglycerides\>1.3\*ULN); hormones(T4, T3, T4, TSH\<0.8\*LLN,\>1.2\*ULN)

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=5 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=6 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=6 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=6 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Number of Participants With Laboratory Abnormalities	0 participants	0 participants	0 participants	1 participants	1 participants	6 participants	6 participants	4 participants	3 participants	3 participants	6 participants

PRIMARY outcome

Timeframe: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Following parameters were analyzed for examination of vital signs: supine systolic and diastolic blood pressure, pulse rate and body temperature.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants Participants received placebo matched to PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 3 mg n=5 Participants Participants received 3 mg oral solution of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 12 mg n=6 Participants Participants received 12 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 40 mg n=6 Participants Participants received 40 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part A: PF-06751979 160 mg n=6 Participants Participants received 160 mg oral suspension of PF-06751979 in either 1 of the 4 intervention periods in Part A. A washout period of at least 7 days was maintained between each intervention period.	Part B: Placebo n=8 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 5 mg n=8 Participants Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B- PF-06751979 15 mg n=8 Participants Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part B: PF-06751979 50 mg n=8 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: Placebo n=4 Participants Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.	Part C: PF-06751979 50 mg n=10 Participants Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.

Continuous cardiac telemetry was conducted in participants. All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern. In this outcome measure, number of participants who had cardiac rhythms of potential clinical concern (based on physician's discretion) were reported.