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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02509117
• Collaborator: (none)
• Enrollment: 55
• Locations: 2
• Arms: 5
• Actual Duration (Months): 12
• Patients Per Site: 27.5
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, PK and PD of PF-06751979 following oral doses in healthy adult and healthy elderly subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: PF-06751979 single ascending dose; Drug: Placebo single dose; Drug: PF-06751979 multiple ascending dose; Drug: Placebo multiple dose; Drug: PF-06751979 multiple dose; Drug: PF-06751979 multiple dose	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Randomized, Double-blind, Sponsor-open, Placebo Controlled First-in-human Trial To Evaluate The Safety,Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06751979 After Oral Administration Of Single And Multiple Ascending Doses To Healthy Adult And Elderly Subjects
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Ascending Dose Cross-over Single Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).	Drug: PF-06751979 single ascending dose; PF-06751979 administered as a single dose (solution/suspension) in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF-06751979). The dose levels are 3 mg, 12 mg, 40 mg, 160 mg.; Drug: Placebo single dose; Matched Placebo solution/suspension administered as single dose.
Experimental: Multiple Ascending Dose PF-06751979 Multiple dose administration to Healthy Subjects in parallel cohorts(PF-06751979)	Drug: PF-06751979 multiple ascending dose; PF-06751979 (solution/suspension) administered daily for 14 consecutive days to parallel cohorts. The dose levels are 5 mg, 15 mg, 50 mg.
Placebo Comparator: Multiple Ascending Dose Placebo Multiple dose administration to Healthy Subjects in parallel cohorts(Placebo)	Drug: Placebo multiple dose; Matched Placebo (solution/suspension)administered daily for 14 consecutive days.; Drug: PF-06751979 multiple dose; Matched Placebo (suspension/solution) administered daily for 14 consecutive days to parallel cohorts.
Experimental: Multiple Dose Elderly PF-06751979 Multiple dose administration to Healthy Elderly Subjects (PF-06751979)	Drug: PF-06751979 multiple dose; PF-06751979 (solution/suspension) administered daily for 14 consecutive days. The dose level is 50 mg.
Placebo Comparator: Multiple Dose Elderly Placebo Multiple dose administration to Healthy Elderly Subjects (Placebo)	Drug: Placebo multiple dose; Matched Placebo (solution/suspension)administered daily for 14 consecutive days.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days]

   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.

2. Number of Participants With Abnormal Physical Examinations Findings [Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days]

   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.

3. Number of Participants With Abnormal Neurological Examinations Findings [Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days]

   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.

4. Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline [Baseline]

   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.

5. Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 [Day 7]

   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.

6. Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 [Day 14]

   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.

7. Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 [Day 19]

   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.

8. Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days]

   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.

9. Number of Participants With Laboratory Abnormalities [Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days]

   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)

10. Number of Participants With Clinically Significant Changes From Baseline in Vital Signs [Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days]

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

11. Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry [Day 1]

    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.

Secondary Outcome Measures

1. Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

2. Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

   AUClast is the area under the plasma concentration time-curve from time zero to the time of last quantifiable concentration.

3. Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

4. Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

   Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.

5. Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

   AUClast(dn) was calculated by dividing AUClast by the exact dose of PF-06751979 (in mg) administered.

6. Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

   AUCinf(dn) was calculated by dividing AUCinf by the exact dose of PF-06751979 (in mg) administered.

7. Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

8. Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

   Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.

9. Part A: Apparent Oral Clearance (CL/F) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

   Drug clearance is the quantitative measure of the rate at which a drug substance is removed from the blood.

10. Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1]

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

11. Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

12. Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

13. Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14]

    Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.

14. Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

15. Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.

16. Part B: Apparent Oral Clearance (CL/F) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood.

17. Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

18. Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14]

    Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.

19. Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.

20. Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14]

    Rac for AUCtau for Day 7 was calculated as: AUCtau on Day 7 divided by AUCtau on Day 1. Rac for AUCtau for Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1.

21. Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    Rac for Cmax for Day 7 was calculated as: Cmax on Day 7 divided by Cmax on Day 1. Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.

22. Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14]

    Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.

23. Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) [0-24 hours on Day 14]

    Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.

24. Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) [0-24 hours on Day 14]

    Aetau% was calculated as: 100*Aetau/dose. Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.

25. Part B: Renal Clearance of PF-06751979 [0-24 hours on Day 14]

    Renal clearance was calculated as amount of drug excreted unchanged in urine during the dosing interval tau (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.

26. Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 [Baseline, Day 14]

    ABeta is the peptide fragment of the amyloid precursor protein. Percent change from baseline in CSF concentration of ABeta fragments (ABeta x-40, ABeta 1-40 and ABeta total) at Day 14 was reported in this outcome measure.

27. Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14]

28. Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14]

    Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.

29. Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

30. Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.

31. Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14]

    Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.

32. Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

33. Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

34. Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14]

    PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.

35. Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14]

    Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1, where Cmax was the maximum observed plasma concentration.

36. Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14]

    Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.

37. Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14]

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

38. Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 [predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14]

    Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years or between the ages of 60 and 85 years, inclusive.

• Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lbs) at Screening.

• Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

• Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

• Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.

• Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.

• Any severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Clinical Trials Medical Group, Inc	Glendale	California	United States	91206
2	Glendale Adventist Medical Center	Glendale	California	United States	91206

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02509117
• Other Study ID Numbers: B8271001
• First Posted: Jul 27, 2015
• Last Update Posted: Nov 1, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by Pfizer: Alzheimer's disease

Study Results

Participant Flow

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

Arm/Group Title	Part A- PF-06751979: 3 mg, 12 mg, 40 mg, Placebo	Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg	Part A- PF-06751979: 3 mg, Placebo, PF-06751979: 40 mg, 160 mg	Part A: Placebo, PF-06751979: 12 mg, 40 mg, 160 mg	Part B- Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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 Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	2	2	2	8	8	8	8	4	10
Treated	2	1	2	2	8	8	8	8	4	10
COMPLETED	2	1	2	2	8	8	8	8	4	8
NOT COMPLETED	0	1	0	0	0	0	0	0	0	2
Period Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	1	2	2	0	0	0	0	0	0
COMPLETED	2	1	2	2	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	2	2	2	0	0	0	0	0	0
Treated	2	2	2	2	0	0	0	0	0	0
COMPLETED	2	2	2	2	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	2	2	2	0	0	0	0	0	0
COMPLETED	2	2	2	2	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	2	2	2	0	0	0	0	0	0
COMPLETED	2	2	2	2	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	2	2	2	0	0	0	0	0	0
COMPLETED	2	2	2	2	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: Period 1-Part A:4 Days; Part B,C:19 Days
STARTED	2	2	2	2	0	0	0	0	0	0
COMPLETED	2	2	2	2	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A- PF-06751979: 3 mg, 12 mg, 40 mg, Placebo	Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg	Part A- PF-06751979: 3 mg, Placebo, PF-06751979: 40 mg, 160 mg	Part A: Placebo, PF-06751979: 12 mg, 40 mg, 160 mg	Part B- Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg	Total
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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 of all reporting groups
Overall Participants	2	3	2	2	8	8	8	8	4	10	55
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	3 100%	2 100%	2 100%	8 100%	8 100%	8 100%	8 100%	1 25%	1 10%	43 78.2%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	3 75%	9 90%	12 21.8%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	3 75%	6 60%	9 16.4%
Male	2 100%	3 100%	2 100%	2 100%	8 100%	8 100%	8 100%	8 100%	1 25%	4 40%	46 83.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6	8	8	8	8	4	10
AEs	0 0%	1 33.3%	0 0%	0 0%	0 0%	1 12.5%	1 12.5%	2 25%	1 25%	3 30%	7 12.7%
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Abnormal Physical Examinations Findings
Description	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.
Time Frame	Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	3 75%	0 0%	1 1.8%

3. Primary Outcome

Title	Number of Participants With Abnormal Neurological Examinations Findings
Description	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.
Time Frame	Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	2 25%	0 0%	0 0%	0 0%	0 0%	2 3.6%

4. Primary Outcome

Title	Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
Description	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.
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
Description	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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19
Description	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.
Time Frame	Day 19

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.
Measure Participants	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Description	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.
Time Frame	Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

9. Primary Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	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)
Time Frame	Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	1 50%	1 12.5%	6 75%	6 75%	4 50%	3 75%	3 30%	6 10.9%

10. Primary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Description	Following parameters were analyzed for examination of vital signs: supine systolic and diastolic blood pressure, pulse rate and body temperature.
Time Frame	Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg	Part C: Placebo	Part C: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6	8	8	8	8	4	10
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

11. Primary Outcome

Title	Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry
Description	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.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A: Placebo	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	8	5	6	6	6
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	5	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]	8.411 (14)	27.36 (36)	78.66 (30)	530.8 (41)

13. Secondary Outcome

Title	Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979
Description	AUClast is the area under the plasma concentration time-curve from time zero to the time of last quantifiable concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	5	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter]	258.6 (16)	1015 (29)	2782 (28)	16890 (18)

14. Secondary Outcome

Title	Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

PK parameter population: all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed'= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	5	5	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter]	289.7 (8)	1142 (25)	3121 (25)	17050 (18)

15. Secondary Outcome

Title	Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979
Description	Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	5	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [[nanogram/milliliter]/milligram]	2.804 (14)	2.280 (35)	1.967 (30)	3.318 (41)

16. Secondary Outcome

Title	Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979
Description	AUClast(dn) was calculated by dividing AUClast by the exact dose of PF-06751979 (in mg) administered.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

PK parameter population: all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	5	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [[nanogram*hour/milliliter]/milligram]	86.25 (16)	84.56 (29)	69.53 (28)	105.5 (18)

17. Secondary Outcome

Title	Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979
Description	AUCinf(dn) was calculated by dividing AUCinf by the exact dose of PF-06751979 (in mg) administered.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

PK parameter population: all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed'= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	5	5	6
Geometric Mean (Geometric Coefficient of Variation) [[nanogram*hour/milliliter]/milligram]	96.51 (8)	95.10 (25)	77.92 (25)	106.6 (18)

18. Secondary Outcome

Title	Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	5	6	6	6
Median (Full Range) [hours]	4.03 (8)	4.11 (25)	4.08 (25)	3.03 (18)

19. Secondary Outcome

Title	Part A: Plasma Decay Half-Life (t1/2) of PF-06751979
Description	Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	5	5	6
Mean (Standard Deviation) [hours]	29.30 (0.60000)	32.94 (4.9176)	32.12 (3.6403)	39.33 (8.1997)

20. Secondary Outcome

Title	Part A: Apparent Oral Clearance (CL/F) of PF-06751979
Description	Drug clearance is the quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	5	5	6
Geometric Mean (Geometric Coefficient of Variation) [milliliter per minute]	172.3 (8)	175.0 (25)	213.4 (25)	156.3 (18)

21. Secondary Outcome

Title	Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Part A: PF-06751979 3 mg	Part A: PF-06751979 12 mg	Part A: PF-06751979 40 mg	Part A: PF-06751979 160 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	3	5	5	6
Geometric Mean (Geometric Coefficient of Variation) [Liter]	436.8 (6)	494.8 (20)	591.4 (26)	523.3 (25)

22. Secondary Outcome

Title	Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Liter]	628.7 (18)	573.2 (12)	629.0 (27)

23. Secondary Outcome

Title	Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 1	10.12 (22)	28.90 (22)	120.6 (17)
Day 7	20.68 (22)	64.34 (12)	241.1 (20)
Day 14	22.41 (23)	64.63 (14)	245.7 (21)

24. Secondary Outcome

Title	Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
Description	Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 1	167.7 (18)	478.8 (20)	1739 (14)
Day 7	395.2 (20)	1149 (12)	4181 (20)
Day 14	422.2 (20)	1152 (13)	4236 (24)

25. Secondary Outcome

Title	Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 1	3.98 (18)	4.07 (20)	2.99 (14)
Day 7	6.02 (20)	4.02 (12)	3.83 (20)
Day 14	4.01 (20)	4.05 (13)	3.00 (24)

26. Secondary Outcome

Title	Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
Description	Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 1	2.024 (22)	1.926 (22)	2.410 (17)
Day 7	4.137 (22)	4.291 (12)	4.821 (20)
Day 14	4.482 (23)	4.307 (14)	4.915 (21)

27. Secondary Outcome

Title	Part B: Apparent Oral Clearance (CL/F) of PF-06751979
Description	Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 7	210.8 (20)	217.8 (12)	199.2 (20)
Day 14	197.1 (20)	216.9 (12)	196.9 (24)

28. Secondary Outcome

Title	Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 7	11.30 (22)	32.09 (11)	125.9 (19)
Day 14	12.55 (22)	32.75 (14)	120.4 (25)

29. Secondary Outcome

Title	Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
Description	Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 1	33.56 (18)	31.94 (20)	34.79 (13)
Day 7	79.04 (20)	76.56 (12)	83.63 (20)
Day 14	84.42 (20)	76.78 (12)	84.69 (24)

30. Secondary Outcome

Title	Part B: Peak-to-Trough Ratio (PTR) of PF-06751979
Description	PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 7	1.830 (8)	2.004 (6)	1.914 (10)
Day 14	1.787 (10)	1.973 (6)	2.043 (10)

31. Secondary Outcome

Title	Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14
Description	Rac for AUCtau for Day 7 was calculated as: AUCtau on Day 7 divided by AUCtau on Day 1. Rac for AUCtau for Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 7	2.355 (15)	2.400 (12)	2.403 (14)
Day 14	2.519 (12)	2.406 (14)	2.434 (15)

32. Secondary Outcome

Title	Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14
Description	Rac for Cmax for Day 7 was calculated as: Cmax on Day 7 divided by Cmax on Day 1. Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Day 7	2.044 (21)	2.225 (14)	2.000 (24)
Day 14	2.213 (17)	2.236 (16)	2.038 (23)

33. Secondary Outcome

Title	Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
Description	Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Mean (Standard Deviation) [hours]	37.15 (5.2041)	30.65 (3.1942)	37.36 (5.9074)

34. Secondary Outcome

Title	Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Description	Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.
Time Frame	0-24 hours on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [milligram]	0.5090 (37)	1.078 (54)	4.193 (37)

35. Secondary Outcome

Title	Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
Description	Aetau% was calculated as: 100*Aetau/dose. Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.
Time Frame	0-24 hours on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Percentage of dose excreted]	10.18 (37)	7.181 (54)	8.395 (37)

36. Secondary Outcome

Title	Part B: Renal Clearance of PF-06751979
Description	Renal clearance was calculated as amount of drug excreted unchanged in urine during the dosing interval tau (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time Frame	0-24 hours on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.

Arm/Group Title	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [milliliter per minute]	20.10 (40)	15.58 (57)	16.51 (48)

37. Secondary Outcome

Title	Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14
Description	ABeta is the peptide fragment of the amyloid precursor protein. Percent change from baseline in CSF concentration of ABeta fragments (ABeta x-40, ABeta 1-40 and ABeta total) at Day 14 was reported in this outcome measure.
Time Frame	Baseline, Day 14

Outcome Measure Data

Analysis Population Description

The pharmacodynamic CSF concentration population was defined as all enrolled and treated participants who had at least 1 measureable CSF ABeta concentration. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.

Arm/Group Title	Part B: Placebo	Part B- PF-06751979 5 mg	Part B- PF-06751979 15 mg	Part B: PF-06751979 50 mg
Arm/Group Description	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.	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.	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.	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.
Measure Participants	8	8	8	8
ABeta 1-40	-5.244 (0.0454)	-60.827 (0.0453)	-69.703 (0.0473)	-86.878 (0.0466)
ABeta x-40	-4.368 (0.0395)	-43.154 (0.0394)	-53.492 (0.0396)	-61.348 (0.0394)
ABeta Total	-0.489 (0.0708)	-37.680 (0.0720)	-45.287 (0.0708)	-61.984 (0.0722)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 3 mg
	Comments	ABeta 1-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-58.659
	Confidence Interval	(2-Sided) 80%; -61.95 to -55.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0642
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 12 mg
	Comments	ABeta 1-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-68.026
	Confidence Interval	(2-Sided) 80%; -70.66 to -65.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0665
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 40 mg
	Comments	ABeta 1-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-86.152
	Confidence Interval	(2-Sided) 80%; -87.26 to -84.95
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0643
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 3 mg
	Comments	ABeta x-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-40.558
	Confidence Interval	(2-Sided) 80%; -44.70 to -36.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0558
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 12 mg
	Comments	ABeta x-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-51.368
	Confidence Interval	(2-Sided) 80%; -54.78 to -47.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0561
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 40 mg
	Comments	ABeta x-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-59.583
	Confidence Interval	(2-Sided) 80%; -62.40 to -56.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0558
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 3 mg
	Comments	ABeta Total: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-37.373
	Confidence Interval	(2-Sided) 80%; -45.06 to -28.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1007
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 12 mg
	Comments	ABeta Total: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-45.018
	Confidence Interval	(2-Sided) 80%; -51.72 to -37.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1001
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Part A: Placebo, Part A: PF-06751979 40 mg
	Comments	ABeta Total: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-61.797
	Confidence Interval	(2-Sided) 80%; -66.51 to -56.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1014
	Estimation Comments

38. Secondary Outcome

Title	Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	10
Day 1	102.9 (25)
Day 14	256.4 (23)

39. Secondary Outcome

Title	Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
Description	Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies participants who were evaluable at specified time points. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	10
Day 1	1621 (22)
Day 14	4505 (20)

40. Secondary Outcome

Title	Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	10
Day 1	4.00
Day 14	4.00

41. Secondary Outcome

Title	Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
Description	Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	10
Day 1	2.059 (25)
Day 14	5.129 (23)

42. Secondary Outcome

Title	Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
Description	Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies participants who were evaluable at specified time points. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	10
Day 1	32.44 (22)
Day 14	90.10 (20)

43. Secondary Outcome

Title	Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14
Description	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [milliliter per minute]	184.9 (20)

44. Secondary Outcome

Title	Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter]	135.8 (18)

45. Secondary Outcome

Title	Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14
Description	PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ratio]	1.887 (9)

46. Secondary Outcome

Title	Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14
Description	Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1, where Cmax was the maximum observed plasma concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ratio]	2.821 (14)

47. Secondary Outcome

Title	Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14
Description	Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [ratio]	2.504 (12)

48. Secondary Outcome

Title	Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [Liter]	637.4 (23)

49. Secondary Outcome

Title	Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
Description	Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
Time Frame	predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14

Outcome Measure Data

Analysis Population Description

The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Part C: PF-06751979 50 mg
Arm/Group Description	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.
Measure Participants	8
Mean (Standard Deviation) [hours]	39.95 (3.1794)

Adverse Events

Time Frame	Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days
Adverse Event Reporting Description	Three non-serious adverse events in Part C (fatigue and dry mouth in 1 subject on 50 mg PF-06751979 and pinched finger in another subject on placebo) were reported after database lock and are not reflected in the results posted.
Arm/Group Title	Part A: Placebo		Part A: PF-06751979 3 mg		Part A: PF-06751979 12 mg		Part A: PF-06751979 40 mg		Part A: PF-06751979 160 mg		Part B: Placebo		Part B- PF-06751979 5 mg		Part B- PF-06751979 15 mg		Part B: PF-06751979 50 mg		Part C: Placebo		Part C: PF-06751979 50 mg
Arm/Group Description	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.		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.		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.		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.		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.		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.		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.		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.		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.		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.		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.
All Cause Mortality
	Part A: Placebo		Part A: PF-06751979 3 mg		Part A: PF-06751979 12 mg		Part A: PF-06751979 40 mg		Part A: PF-06751979 160 mg		Part B: Placebo		Part B- PF-06751979 5 mg		Part B- PF-06751979 15 mg		Part B: PF-06751979 50 mg		Part C: Placebo		Part C: PF-06751979 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Placebo		Part A: PF-06751979 3 mg		Part A: PF-06751979 12 mg		Part A: PF-06751979 40 mg		Part A: PF-06751979 160 mg		Part B: Placebo		Part B- PF-06751979 5 mg		Part B- PF-06751979 15 mg		Part B: PF-06751979 50 mg		Part C: Placebo		Part C: PF-06751979 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Placebo		Part A: PF-06751979 3 mg		Part A: PF-06751979 12 mg		Part A: PF-06751979 40 mg		Part A: PF-06751979 160 mg		Part B: Placebo		Part B- PF-06751979 5 mg		Part B- PF-06751979 15 mg		Part B: PF-06751979 50 mg		Part C: Placebo		Part C: PF-06751979 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		1/5 (20%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		1/8 (12.5%)		2/8 (25%)		1/8 (12.5%)		3/4 (75%)		7/10 (70%)
Gastrointestinal disorders
Abdominal pain	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/4 (25%)		0/10 (0%)
Abnormal faeces	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/4 (25%)		0/10 (0%)
General disorders
Oedema peripheral	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		0/10 (0%)
Fatigue	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Vessel puncture site haematoma	0/8 (0%)		1/5 (20%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		0/10 (0%)
Infections and infestations
Upper respiratory tract infection	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Investigations
Liver function test abnormal	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/4 (0%)		0/10 (0%)
Urine analysis abnormal	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Musculoskeletal stiffness	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Pain in extremity	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Nervous system disorders
Dizziness	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Dysarthria	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Dysgeusia	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Headache	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/8 (0%)		1/4 (25%)		1/10 (10%)
Psychiatric disorders
Hallucination, auditory	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		0/10 (0%)
Abnormal dreams	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		2/10 (20%)
Insomnia	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Renal and urinary disorders
Urine flow decreased	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/4 (0%)		0/10 (0%)
Chromaturia	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/4 (25%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Rash	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/4 (0%)		1/10 (10%)
Skin odour abnormal	0/8 (0%)		0/5 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		1/4 (25%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.