Clinical Trial In Healthy Volunteers And Health Elderly Volunteers To Evaluate The Safety, Tolerability And Blood Concentration After Single And Multiple Escalating Oral Doses Of PF-06751979.

Phase 1

Completed

Conditions: Healthy Subjects

Interventions: Drug: PF-06751979 multiple ascending dose
Drug: PF-06751979 single dose
Drug: PF-06751979 multiple dose
Drug: Placebo multiple ascending dose
Drug: Placebo single dose
Drug: Placebo multiple elderly dose

Registration Number: NCT02793232

Lead Sponsor: Pfizer

Brief Summary: This study will test the safety, tolerability and blood concentrations of single and multiple oral doses of PF-06751979 in health subjects and healthy elderly subjects. PF-06751979 is being developed for the treatment of Alzheimer's disease.

Detailed Description: The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of PF-06751979 following oral doses in healthy adult and healthy elderly subjects at higher doses than previously administered. Such characteristics will enable the design of future clinical trials in patient population, in the effort to optimize the efficacy of PF-06751979, as well as to establish safety margins in humans. Inclusion of healthy elderly subjects will be optional, but can provide additional safety and tolerability information in the age range of the target population while confirming the PK of PF-06751979 in these subjects for future clinical trials in the Alzheimer's disease patient population.

The Primary Objective is to evaluate the safety and tolerability of single and multiple ascending oral doses of PF-06751979 in healthy adult subjects. Secondary Objectives are to characterize the pharmacokinetics of PF-06751979 in: plasma following single and multiple ascending oral dose administration in healthy adult subjects and urine following multiple ascending oral dose administration in healthy adult subjects. An additional secondary objective is to evaluate the effect of multiple oral doses of PF 06751979 on CSF A-beta fragments in healthy adult subjects.

This study is divided into three parts: Part A - Single ascending doses (SAD) healthy adult subjects (18-55 years); Part B - Multiple ascending doses (MAD) in healthy adult subjects (18-55 years); Part C - Multiple doses (MD) in healthy elderly subjects (60-85 years). Study Parts may be run in a staggered fashion; Part C of the study may commence after satisfactory review of relevant data from Parts A and B.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

Healthy female subjects of non childbearing potential and male subjects.
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 (32 kg/m2 for healthy elderly); 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.
Additional criterion for subjects of Japanese descent who may be enrolled in Part B (multiple ascending dose cohorts in healthy subjects): Japanese subjects who have four Japanese grandparents born in Japan.

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 the 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 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Multiple Ascending Dose	PF-06751979 multiple ascending dose	Multiple dose administration to Healthy Subjects in parallel cohorts (PF-06751979).
Multiple Ascending Dose	Placebo multiple ascending dose	Multiple dose administration to Healthy Subjects in parallel cohorts (PF-06751979).
Single Ascending Dose Crossover	PF-06751979 single dose	Single Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).
Single Ascending Dose Crossover	Placebo single dose	Single Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).
Multiple Dose Elderly	PF-06751979 multiple dose	Multiple dose administration to Healthy Elderly Subjects (PF-06751979). This cohort is optional.
Multiple Dose Elderly	Placebo multiple elderly dose	Multiple dose administration to Healthy Elderly Subjects (PF-06751979). This cohort is optional.

Primary Outcome Measures

Name	Time	Method
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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 measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at Day 14 were reported.
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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 measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at Day 19 were reported.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days	Criteria for abnormal values of ECG parameters: maximum pulse rate (PR) interval greater than or equal to (\>=)300 milliseconds (msec); maximum PR interval increase from baseline (IFB): \>=25 percent (%) when baseline was greater than (\>)200 msec; or \>=50 % when baseline was greater than (\>)200 msec, maximum QRS interval \>=140 msec and QRS interval IFB: \>=50%. QT interval using Fridericia's correction (QTcF) ranges from 450 msec to maximum less than (\<)480 msec, less than or equal to (\<=) 480 msec to maximum \<500 msec and maximum \>=500 msec, maximum QTcF interval IFB range from \<=30 to \<60 msec and maximum \>=60 msec. Only categories which included at least 1 participant with abnormality are reported in this outcome measure.
Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry	Day 1	In all Periods of Part A, continuous cardiac monitoring was maintained for 8 hours (or longer if considered clinically necessary by the investigator) following dose administration on Day 1. All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern.
Number of Participants With Vital Sign Abnormalities	Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days	Criteria for vital signs abnormalities: systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), diastolic blood pressure (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm). Maximum IFB in Supine SBP \>=30 mmHg, Maximum decrease from baseline (DFB) in Supine SBP \>=30 mmHg, maximum DFB in Supine DBP \>=20 mmHg.
Number of Participants With Laboratory Abnormalities	Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 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 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).
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 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 and up to the follow up visit (up to 36 days in Part A, 49 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	Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days	Full physical examination included head, ears, eyes, nose, mouth, skin, heart, lung, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Abnormality in physical examinations was based on investigator's discretion.
Number of Participants With Abnormal Neurological Examinations Findings	Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 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 the 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.
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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 measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at Day 7 were reported.

Secondary Outcome Measures

Name	Time	Method
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	Area under the plasma concentration-time profile from time zero to the time of last measured concentration (AUClast).
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	Cmax(dn) was obtained calculated by dividing Cmax by the exact dose of PF-06751979 (in milligram) administered to a participant.
Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 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 blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 14	Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	AUClast(dn) was calculated by dividing AUClast by the exact dose of PF-06751979 (in mg) administered to a participant. AUClast was area under the plasma concentration-time profile from time zero to the time of last measured concentration.
Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	AUCinf (dn) was calculated by dividing AUCinf by the exact dose of PF-06751979 (in mg) administered to a participant. AUCinf was area under the plasma concentration-time profile from time zero extrapolated to infinite time (0-inf).
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Part A: Plasma Decay Half-Life (t1/2) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	Plasma decay half-life is the time duration for the plasma concentration of PF-06751979 to decrease by one-half of its original concentration.
Part A: Apparent Clearance (CL/F) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 14	Area under the concentration curve from time zero to end of dosing interval (AUCtau), 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.
Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 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.
Part B: Plasma Decay Half-Life (t1/2) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Plasma decay half-life is the time duration for the plasma concentration of PF-06751979 to decrease by one-half of its original concentration.
Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Cmax(dn) was obtained calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered to a participant.
Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Part B: Apparent Clearance (CL/F) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Part B: Peak-to-Trough Ratio of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Peak-to-trough ratio was calculated by dividing Cmax with Cmin of PF-06751979. Cmax was maximum plasma concentration during the dosing interval and Cmin was minimum observed plasma concentration during the dosing interval.
Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 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 blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 7; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Rac for Cmax on Day 7 was calculated as: Cmax on Day 7 divided by Cmax on Day 1 and Rac for Cmax on Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 14	Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Cmax(dn) was obtained calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered to a participant.
Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 14	Area under the concentration curve from time zero to end of dosing interval (AUCtau), 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.
Part C: Apparent Oral Clearance (CL/F)	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Minimum observed concentration during the dosing interval.
Part C: Peak-to-Trough Ratio of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Peak-to-trough ratio was calculated by dividing Cmax with Cmin of PF-06751979. Cmax was maximum plasma concentration during the dosing interval and Cmin was minimum observed plasma concentration during the dosing interval.
Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 14	Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1.
Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose on Day 1; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Rac for Cmax on Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
Part C: Plasma Decay Half-Life (t1/2) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14	Plasma decay half-life was the time duration for the plasma concentration to decrease by one-half of its original concentration.
Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979	pre-dose, 0.5, 1, 2, 4, 6, 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 blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)	0-24 hours on Day 14	Aetau was the amount of drug excreted unchanged in urine during the dosing interval tau, where tau was 24 hours.
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 was the amount of drug excreted unchanged in urine during the dosing interval tau, where tau was 24 hours.
Part B: Renal Clearance of PF-06751979	0-24 hours on Day 14	Renal clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated in urine. It 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.
Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments	Baseline, Day 14	ABeta is the peptide fragment of the amyloid precursor protein. Percent change from baseline in CSF concentration of ABeta fragments (ABeta 1-38, ABeta 1-40, ABeta 1-42, ABeta total, ABeta x-38, ABeta x-40, ABeta x-42, soluble amyloid precursor protein alpha (sAPP-alpha), soluble amyloid precursor protein beta (sAPP-beta) at Day 14 was reported in this outcome measure.