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

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

时间窗: 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.

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

时间窗: 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.

Number of Participants With Abnormal Neurological Examinations Findings

时间窗: 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.

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

时间窗: 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.

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

时间窗: 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.

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: 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.

Number of Participants With Abnormal Physical Examinations Findings

时间窗: 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.

Number of Participants With Laboratory Abnormalities

时间窗: 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)

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

时间窗: 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.

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

时间窗: 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.

Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry

时间窗: 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.