Healthy Subjects
Conditions
Keywords
Safety, Tolerability, Pharmacokinetics, Alzheimer's disease
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.
Interventions
DRUGPF-06751979 single dose
PF-06751979 administered as a single dose suspension in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF 06751979). The planned dose levels are 200 mg, 400 mg, 700 mg, 200 mg fed (these doses are subject to change based on emerging data).
Matched Placebo suspension administered as single dose
PF-06751979 suspension administered daily for 14 consecutive days to parallel cohorts. The planned dose levels are mg, 100 mg, 200 mg, 340 mg (these are subject to change based on emerging data).
Matched placebo suspension administered daily for 14 consecutive days.
PF-06751979 suspension administered daily for 14 consecutive days. The planned dose level is 340 mg (this is subject to change based on emerging data).
DRUGPlacebo multiple elderly dose
Multiple dose administration to Healthy Elderly Subjects (Placebo)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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: 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: 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: 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 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: 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 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 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 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 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. |
| 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 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: 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 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 | — |
Countries
Belgium
Participant flow
Pre-assignment details
Study was conducted in 3 parts: Part A (4-period cross-over design), Part B and C (single period, parallel design).
Participants by arm
| Arm | Count |
|---|---|
| Part A- Placebo, PF-06751979: 400 mg, 540 mg, 200 mg Fed Participants received oral dose of placebo matched to PF-06751979 on Day 1 of intervention period 1 followed by oral dose of PF-06751979 400 milligram (mg) suspension on Day 1 of intervention period 2 followed by oral dose of PF-06751979 540 mg suspension on Day 1 of intervention period 3 followed by an oral dose of PF-06751979 200 mg suspension under fed condition on Day 1 of intervention period 4. A washout period of at least 10 days was maintained between each intervention period. All doses were administered in fasted state except PF-06751979 200 mg Fed. After completion of period 4, participants were followed for 10 days. | 2 |
| Part A-PF-06751979 200mg,Placebo,PF-06751979 540 mg,200 mg Fed Participants received oral dose of PF-06751979 200 mg suspension on Day 1 of intervention period 1 followed by oral dose of placebo matched to PF-06751979 on Day 1 of intervention period 2 followed by oral dose of PF-06751979 540 mg suspension on Day 1 of intervention period 3 followed by an oral dose of PF-06751979 200 mg suspension under fed condition on Day 1 of intervention period 4. A washout period of at least 10 days was maintained between each intervention period. All doses were administered in fasted state except PF-06751979 200 mg Fed. After completion of period 4, participants were followed for 10 days. | 2 |
| Part A-PF-06751979: 200mg, 400mg,Placebo,PF-06751979 200mg Fed Participants received oral dose of PF-06751979 200 mg suspension on Day 1 of intervention period 1 followed by oral dose of PF-06751979 400 mg suspension on Day 1 of intervention period 2 followed by oral dose of placebo matched to PF-06751979 on Day 1 of intervention period 3 followed by an oral dose of PF-06751979 200 mg suspension under fed condition on Day 1 of intervention period 4. A washout period of at least 10 days was maintained between each intervention period. All doses were administered in fasted state except PF-06751979 200 mg Fed. After completion of period 4, participants were followed for 10 days. | 2 |
| Part A- PF-06751979: 200 mg, 400 mg, 540 mg, Placebo Participants received oral dose of PF-06751979 200 mg suspension on Day 1 of intervention period 1 followed by oral dose of PF-06751979 400 mg suspension on Day 1 of intervention period 2 followed by oral dose of PF-06751979 540 mg suspension on Day 1 of intervention period 3 followed by oral dose of placebo matched to PF-06751979 on Day 1 of intervention period 4. A washout period of at least 10 days was maintained between each intervention period. All doses were administered in fasted state. After completion of period 4, participants were followed for 10 days. | 2 |
| Part B: Placebo Participants received oral dose of placebo matched to PF-06751979 suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to 15 days (up to Day 29) after last dose of study medication. | 7 |
| Part B: PF-06751979 125 mg Participants received oral dose of PF-06751979 125 mg suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to 15 days (up to Day 29) after last dose of study medication. | 12 |
| Part B: PF-06751979 275 mg Participants received oral dose of PF-06751979 275 mg suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to 15 days (up to Day 29) after last dose of study medication. | 9 |
| Part C: Placebo Participants received oral dose of placebo matched to PF-06751979 suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to 15 days (up to Day 29) after last dose of study medication. | 2 |
| Part C: PF-06751979 125 mg Participants received oral dose of PF-06751979 125 mg suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to 15 days (up to Day 29) after last dose of study medication. | 8 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Period 1-Part A:5 Days; Part B,C:19 Days | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A- Placebo, PF-06751979: 400 mg, 540 mg, 200 mg Fed | Part A-PF-06751979 200mg,Placebo,PF-06751979 540 mg,200 mg Fed | Part A-PF-06751979: 200mg, 400mg,Placebo,PF-06751979 200mg Fed | Part A- PF-06751979: 200 mg, 400 mg, 540 mg, Placebo | Part B: Placebo | Part B: PF-06751979 125 mg | Part B: PF-06751979 275 mg | Part C: Placebo | Part C: PF-06751979 125 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 12 Participants | 9 Participants | 0 Participants | 2 Participants | 38 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 12 Participants | 9 Participants | 1 Participants | 5 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 12 | 0 / 9 | 0 / 2 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 3 / 6 | 2 / 6 | 6 / 6 | 4 / 6 | 6 / 7 | 10 / 12 | 8 / 9 | 2 / 2 | 6 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 12 | 0 / 9 | 0 / 2 | 0 / 8 |
Outcome results
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
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.
Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part A: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 1 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part B: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part B: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 1 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 1 participants |
| Part C: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 0 participants |
| Part C: Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval: 450 to <480 msec | 1 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <=30 to <60 msec | 0 participants |
Primary
Number of Participants With Abnormal Neurological Examinations Findings
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 36 days; Part B and C: Baseline up to 49 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part B: Placebo | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part C: Placebo | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
Primary
Number of Participants With Abnormal Physical Examinations Findings
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.
Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Number of Participants With Abnormal Physical Examinations Findings | 1 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Abnormal Physical Examinations Findings | 5 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part B: Placebo | Number of Participants With Abnormal Physical Examinations Findings | 6 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Abnormal Physical Examinations Findings | 8 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Abnormal Physical Examinations Findings | 5 participants |
| Part C: Placebo | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Abnormal Physical Examinations Findings | 4 participants |
Primary
Number of Participants With Laboratory Abnormalities
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).
Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Number of Participants With Laboratory Abnormalities | 6 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Laboratory Abnormalities | 5 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Laboratory Abnormalities | 2 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Laboratory Abnormalities | 3 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Laboratory Abnormalities | 5 participants |
| Part B: Placebo | Number of Participants With Laboratory Abnormalities | 5 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Laboratory Abnormalities | 11 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Laboratory Abnormalities | 8 participants |
| Part C: Placebo | Number of Participants With Laboratory Abnormalities | 1 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Laboratory Abnormalities | 7 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 participants |
| Part A: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 4 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 10 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 8 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part C: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 participants |
| Part C: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
Number of Participants With Vital Sign Abnormalities
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.
Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part A: Placebo | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part A: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part A: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part A: PF-06751979 200 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part A: PF-06751979 400 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 1 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 540 mg | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part A: PF-06751979 200 mg Fed | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part B: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part B: Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part B: Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part B: Placebo | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part B: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part B: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part B: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 1 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 1 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 1 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 1 participants |
| Part B: PF-06751979 275 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part C: Placebo | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part C: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 0 participants |
| Part C: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 1 participants |
| Part C: Placebo | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 0 participants |
| Part C: Placebo | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 0 participants |
| Part C: Placebo | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 0 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Supine SBP: <90 mmHg | 1 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine DBP: >=20 mmHg | 1 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Maximum DFB in Supine SBP: >=30 mmHg | 2 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Supine DBP: <50 mmHg | 1 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Supine PR: <40 bpm | 0 participants |
| Part C: PF-06751979 125 mg | Number of Participants With Vital Sign Abnormalities | Maximum IFB in Supine SBP: >=30 mmHg | 0 participants |
Primary
Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry
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.
Time frame: Day 1
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 200 mg | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 400 mg | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 540 mg | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 200 mg Fed | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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.
Time frame: Baseline
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 200 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 400 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 540 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 200 mg Fed | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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.
Time frame: Day 14
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 | 0 participants |
| Part A: PF-06751979 200 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 | 0 participants |
| Part A: PF-06751979 400 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 | 0 participants |
| Part A: PF-06751979 540 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 | 0 participants |
| Part A: PF-06751979 200 mg Fed | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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.
Time frame: Day 19
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19 | 0 participants |
| Part A: PF-06751979 200 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19 | 0 participants |
| Part A: PF-06751979 400 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19 | 0 participants |
| Part A: PF-06751979 540 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19 | 0 participants |
| Part A: PF-06751979 200 mg Fed | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 19 | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at 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.
Time frame: Day 7
Population: Safety analysis set included all participants who received at least 1 dose of study medication. Data for this outcome measure was not planned to be analyzed for Part A, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7 | 0 participants |
| Part A: PF-06751979 200 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7 | 0 participants |
| Part A: PF-06751979 400 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7 | 0 participants |
| Part A: PF-06751979 540 mg | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7 | 0 participants |
| Part A: PF-06751979 200 mg Fed | Part B and C: Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS) at Day 7 | 0 participants |
Secondary
Part A: Apparent Clearance (CL/F) of PF-06751979
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Apparent Clearance (CL/F) of PF-06751979 | 145.8 milliliter per minute | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 200 mg | Part A: Apparent Clearance (CL/F) of PF-06751979 | 148.3 milliliter per minute | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 400 mg | Part A: Apparent Clearance (CL/F) of PF-06751979 | 142.0 milliliter per minute | Geometric Coefficient of Variation 9 |
| Part A: PF-06751979 540 mg | Part A: Apparent Clearance (CL/F) of PF-06751979 | 143.3 milliliter per minute | Geometric Coefficient of Variation 15 |
Secondary
Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 433.7 Liter | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 200 mg | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 433.0 Liter | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 400 mg | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 431.1 Liter | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 540 mg | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 408.1 Liter | Geometric Coefficient of Variation 16 |
Secondary
Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979
Area under the plasma concentration-time profile from time zero to the time of last measured concentration (AUClast).
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 20500 nanogram*hour per milliliter | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 200 mg | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 41710 nanogram*hour per milliliter | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 400 mg | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 58190 nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 540 mg | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 20170 nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
Secondary
Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 22850 nanogram*hour per milliliter | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 200 mg | Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 44980 nanogram*hour per milliliter | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 400 mg | Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 63420 nanogram*hour per milliliter | Geometric Coefficient of Variation 9 |
| Part A: PF-06751979 540 mg | Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 23260 nanogram*hour per milliliter | Geometric Coefficient of Variation 15 |
Secondary
Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979 | 102.6 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 200 mg | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979 | 104.2 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 400 mg | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979 | 107.9 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 540 mg | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of PF-06751979 | 100.9 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 13 |
Secondary
Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979
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).
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979 | 114.1 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 200 mg | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979 | 112.4 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 400 mg | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979 | 117.6 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 9 |
| Part A: PF-06751979 540 mg | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf [dn]) of PF-06751979 | 116.4 (nanogram*hour/milliliter) per milligram | Geometric Coefficient of Variation 15 |
Secondary
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979
Cmax(dn) was obtained calculated by dividing Cmax by the exact dose of PF-06751979 (in milligram) administered to a participant.
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | 3.218 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 200 mg | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | 3.592 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 10 |
| Part A: PF-06751979 400 mg | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | 3.387 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 540 mg | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | 3.154 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 9 |
Secondary
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: Pharmacokinetic (PK) parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 643.2 nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 200 mg | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 1436 nanogram per milliliter | Geometric Coefficient of Variation 10 |
| Part A: PF-06751979 400 mg | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 1829 nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 540 mg | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 630.2 nanogram per milliliter | Geometric Coefficient of Variation 9 |
Secondary
Part A: Plasma Decay Half-Life (t1/2) of PF-06751979
Plasma decay half-life is the time duration for the plasma concentration of PF-06751979 to decrease by one-half of its original concentration.
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 35.20 hours | Standard Deviation 8.9731 |
| Part A: PF-06751979 200 mg | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 34.70 hours | Standard Deviation 8.9749 |
| Part A: PF-06751979 400 mg | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 35.85 hours | Standard Deviation 8.1028 |
| Part A: PF-06751979 540 mg | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 33.38 hours | Standard Deviation 6.2474 |
Secondary
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 72 and 96 hours post dose on Day 1
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 4.00 hours | Full Range 17 |
| Part A: PF-06751979 200 mg | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 3.02 hours | Full Range 17 |
| Part A: PF-06751979 400 mg | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 3.01 hours | Full Range 9 |
| Part A: PF-06751979 540 mg | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 6.00 hours | Full Range 15 |
Secondary
Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Aetau was the amount of drug excreted unchanged in urine during the dosing interval tau, where tau was 24 hours.
Time frame: 0-24 hours on Day 14
Population: PK parameter analysis set =all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.Here, number of participants analyzed =participants who were evaluable for this outcome measure.Data for this outcome measure was not planned to be analyzed for Part A and C,as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 12.93 milligram | Geometric Coefficient of Variation 38 |
| Part A: PF-06751979 200 mg | Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 25.93 milligram | Geometric Coefficient of Variation 28 |
Secondary
Part B: Apparent Clearance (CL/F) of PF-06751979
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time point for each arm.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Apparent Clearance (CL/F) of PF-06751979 | Day 7 | 151.0 milliliter per minute | Geometric Coefficient of Variation 16 |
| Part A: Placebo | Part B: Apparent Clearance (CL/F) of PF-06751979 | Day 14 | 149.0 milliliter per minute | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Apparent Clearance (CL/F) of PF-06751979 | Day 7 | 146.9 milliliter per minute | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Apparent Clearance (CL/F) of PF-06751979 | Day 14 | 155.3 milliliter per minute | Geometric Coefficient of Variation 13 |
Secondary
Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 390.5 Liter | Geometric Coefficient of Variation 23 |
| Part A: PF-06751979 200 mg | Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 498.3 Liter | Geometric Coefficient of Variation 27 |
Secondary
Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time frame: 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
Population: Analysis was performed on PK parameter analysis set. Number analyzed= participants evaluable at specified time points for each arm. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 1 | 6380 nanogram*hour per milliliter | Geometric Coefficient of Variation 15 |
| Part A: Placebo | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 7 | 13810 nanogram*hour per milliliter | Geometric Coefficient of Variation 16 |
| Part A: Placebo | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 13990 nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 1 | 13260 nanogram*hour per milliliter | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 200 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 7 | 31210 nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 29470 nanogram*hour per milliliter | Geometric Coefficient of Variation 12 |
Secondary
Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979
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.
Time frame: 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
Population: Analysis was performed on PK parameter analysis set. Number analyzed= participants evaluable at specified time points for each arm. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 1 | 51.04 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 15 |
| Part A: Placebo | Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 7 | 110.4 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 16 |
| Part A: Placebo | Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 14 | 111.8 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 1 | 48.21 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 200 mg | Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 7 | 113.5 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 15 |
| Part A: PF-06751979 200 mg | Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 14 | 107.1 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 12 |
Secondary
Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979
Cmax(dn) was obtained calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered to a participant.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time point for each arm.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 1 | 3.541 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 20 |
| Part A: Placebo | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 7 | 6.549 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 19 |
| Part A: Placebo | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 14 | 6.702 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 16 |
| Part A: PF-06751979 200 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 7 | 7.272 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 1 | 3.576 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 200 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 14 | 6.794 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 14 |
Secondary
Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time points for each arm.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 442.7 nanogram per milliliter | Geometric Coefficient of Variation 20 |
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 7 | 818.7 nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 837.6 nanogram per milliliter | Geometric Coefficient of Variation 16 |
| Part A: PF-06751979 200 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 983.2 nanogram per milliliter | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 200 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 7 | 2000 nanogram per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 1869 nanogram per milliliter | Geometric Coefficient of Variation 14 |
Secondary
Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979
Time frame: 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
Population: Analysis was performed on PK parameter analysis set. Number analyzed= participants evaluable at specified time points for each arm. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 7 | 388.4 nanogram per milliliter | Geometric Coefficient of Variation 17 |
| Part A: Placebo | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 14 | 390.3 nanogram per milliliter | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 200 mg | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 7 | 857.3 nanogram per milliliter | Geometric Coefficient of Variation 15 |
| Part A: PF-06751979 200 mg | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 14 | 868.5 nanogram per milliliter | Geometric Coefficient of Variation 15 |
Secondary
Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979
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.
Time frame: 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
Population: Analysis was performed on PK parameter analysis set. Number analyzed= participants evaluable at specified time points for each arm. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 | Day 7 | 1.849 ratio | Geometric Coefficient of Variation 16 |
| Part A: Placebo | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 | Day 14 | 1.892 ratio | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 200 mg | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 | Day 7 | 2.033 ratio | Geometric Coefficient of Variation 7 |
| Part A: PF-06751979 200 mg | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 | Day 14 | 1.923 ratio | Geometric Coefficient of Variation 9 |
Secondary
Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979
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: 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
Population: Analysis was performed on PK parameter analysis set. Number analyzed= participants evaluable at specified time points for each arm. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 | Day 7 | 2.165 ratio | Geometric Coefficient of Variation 9 |
| Part A: Placebo | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 | Day 14 | 2.190 ratio | Geometric Coefficient of Variation 11 |
| Part A: PF-06751979 200 mg | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 | Day 7 | 2.355 ratio | Geometric Coefficient of Variation 15 |
| Part A: PF-06751979 200 mg | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 | Day 14 | 2.265 ratio | Geometric Coefficient of Variation 11 |
Secondary
Part B: Peak-to-Trough Ratio of PF-06751979
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.
Time frame: 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
Population: Analysis was performed on PK parameter analysis set. Number analyzed= participants evaluable at specified time points for each arm. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Peak-to-Trough Ratio of PF-06751979 | Day 7 | 2.111 ratio | Geometric Coefficient of Variation 10 |
| Part A: Placebo | Part B: Peak-to-Trough Ratio of PF-06751979 | Day 14 | 2.145 ratio | Geometric Coefficient of Variation 11 |
| Part A: PF-06751979 200 mg | Part B: Peak-to-Trough Ratio of PF-06751979 | Day 7 | 2.332 ratio | Geometric Coefficient of Variation 8 |
| Part A: PF-06751979 200 mg | Part B: Peak-to-Trough Ratio of PF-06751979 | Day 14 | 2.151 ratio | Geometric Coefficient of Variation 9 |
Secondary
Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
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.
Time frame: 0-24 hours on Day 14
Population: PK parameter analysis set =all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.Here, number of participants analyzed =participants who were evaluable for this outcome measure.Data for this outcome measure was not planned to be analyzed for Part A and C,as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 10.36 percentage of dose excreated | Geometric Coefficient of Variation 38 |
| Part A: PF-06751979 200 mg | Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 9.429 percentage of dose excreated | Geometric Coefficient of Variation 28 |
Secondary
Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments
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.
Time frame: Baseline, Day 14
Population: Pharmacodynamic CSF concentration population: all enrolled and treated participants who had at least 1 measureable CSF ABeta concentration. Number of participants analyzed= participants who were evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-38 | -12.362 percent change | Standard Error 0.0708 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta total | -7.911 percent change | Standard Error 0.0492 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-42 | -10.874 percent change | Standard Error 0.0539 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-40 | -9.785 percent change | Standard Error 0.0673 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-38 | -4.223 percent change | Standard Error 0.0669 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | sAPP-beta | -5.553 percent change | Standard Error 0.0545 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-42 | -10.335 percent change | Standard Error 0.0789 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-40 | -10.031 percent change | Standard Error 0.0746 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | sAPP-alpha | -8.237 percent change | Standard Error 0.0655 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-40 | -80.998 percent change | Standard Error 0.0478 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-38 | -80.324 percent change | Standard Error 0.0472 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-40 | -85.452 percent change | Standard Error 0.0536 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-42 | -86.383 percent change | Standard Error 0.0587 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-38 | -82.003 percent change | Standard Error 0.0513 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-42 | -81.861 percent change | Standard Error 0.0385 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | sAPP-alpha | 58.653 percent change | Standard Error 0.048 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | sAPP-beta | -81.266 percent change | Standard Error 0.039 |
| Part A: PF-06751979 200 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta total | -80.116 percent change | Standard Error 0.0348 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-42 | -93.607 percent change | Standard Error 0.0758 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-38 | -87.935 percent change | Standard Error 0.0579 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | sAPP-alpha | 81.737 percent change | Standard Error 0.0604 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta 1-40 | -92.927 percent change | Standard Error 0.0689 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta total | -86.523 percent change | Standard Error 0.0428 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-40 | -87.622 percent change | Standard Error 0.0591 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-38 | -90.106 percent change | Standard Error 0.0643 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | sAPP-beta | -84.304 percent change | Standard Error 0.0485 |
| Part A: PF-06751979 400 mg | Part B: Percent Change From Baseline in Cerebrospinal Spinal Fluid (CSF) Amyloid Beta (ABeta) Fragments | ABeta x-42 | -86.618 percent change | Standard Error 0.0472 |
Comparison: ABeta 1-38: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-81.56, -77.11]Mixed Models Analysis
Comparison: ABeta 1-38: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-88.8, -85.84]Mixed Models Analysis
Comparison: ABeta 1-40: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-85.65, -81.78]Mixed Models Analysis
Comparison: ABeta 1-40: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-93.15, -90.98]Mixed Models Analysis
Comparison: ABeta 1-42: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-86.64, -82.74]Mixed Models Analysis
Comparison: ABeta 1-42: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-93.85, -91.74]Mixed Models Analysis
Comparison: ABeta x-38: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-81.69, -76.96]Mixed Models Analysis
Comparison: ABeta x-38: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-90.06, -87.18]Mixed Models Analysis
Comparison: ABeta x-40: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-81.11, -76.52]Mixed Models Analysis
Comparison: ABeta x-40: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-87.82, -84.55]Mixed Models Analysis
Comparison: ABeta x-42: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-81.36, -77.78]Mixed Models Analysis
Comparison: ABeta x-42: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-86.34, -83.5]Mixed Models Analysis
Comparison: sAPP-alpha: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [55.37, 92.4]Mixed Models Analysis
Comparison: sAPP-alpha: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [75.92, 122.96]Mixed Models Analysis
Comparison: sAPP-beta: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-81.84, -78.33]Mixed Models Analysis
Comparison: sAPP-beta: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-84.92, -81.69]Mixed Models Analysis
Comparison: Abeta total: General linear model with treatment, as the fixed effect and loge(baseline) as covariatep-value: <0.000180% CI: [-80.06, -76.62]Mixed Models Analysis
Comparison: Abeta total: General linear model with treatment, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-86.57, -84.05]Mixed Models Analysis
Secondary
Part B: Plasma Decay Half-Life (t1/2) of PF-06751979
Plasma decay half-life is the time duration for the plasma concentration of PF-06751979 to decrease by one-half of its original concentration.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured. Here, number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 | 30.73 hour | Standard Deviation 5.7464 |
| Part A: PF-06751979 200 mg | Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 | 37.79 hour | Standard Deviation 7.7261 |
Secondary
Part B: Renal Clearance of PF-06751979
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.
Time frame: 0-24 hours on Day 14
Population: PK parameter analysis set =all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.Here, number of participants analyzed =participants who were evaluable for this outcome measure.Data for this outcome measure was not planned to be analyzed for Part A and C,as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Renal Clearance of PF-06751979 | 15.54 milliliter per minute | Geometric Coefficient of Variation 37 |
| Part A: PF-06751979 200 mg | Part B: Renal Clearance of PF-06751979 | 14.68 milliliter per minute | Geometric Coefficient of Variation 34 |
Secondary
Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time point for each arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 4.00 hours |
| Part A: Placebo | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 7 | 3.00 hours |
| Part A: Placebo | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 4.00 hours |
| Part A: PF-06751979 200 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 4.00 hours |
| Part A: PF-06751979 200 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 7 | 2.00 hours |
| Part A: PF-06751979 200 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 4.00 hours |
Secondary
Part C: Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Apparent Oral Clearance (CL/F) | 141.4 milliliter per minute | Geometric Coefficient of Variation 23 |
Secondary
Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 496.1 Liter | Geometric Coefficient of Variation 30 |
Secondary
Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979
Area under the plasma concentration versus time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 1 | 5238 nanogram*hour per milliliter | Geometric Coefficient of Variation 24 |
| Part A: Placebo | Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 14750 nanogram*hour per milliliter | Geometric Coefficient of Variation 23 |
Secondary
Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979
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.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 1 | 41.93 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 24 |
| Part A: Placebo | Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau[dn]) of PF-06751979 | Day 14 | 118.0 (nanogram*hour/milliliter)/milligram | Geometric Coefficient of Variation 23 |
Secondary
Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979
Cmax(dn) was obtained calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered to a participant.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 1 | 3.019 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 30 |
| Part A: Placebo | Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of PF-06751979 | Day 14 | 7.035 (nanogram per milliliter) per milligram | Geometric Coefficient of Variation 28 |
Secondary
Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 377.1 nanogram per milliliter | Geometric Coefficient of Variation 30 |
| Part A: Placebo | Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 879.4 nanogram per milliliter | Geometric Coefficient of Variation 28 |
Secondary
Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979
Minimum observed concentration during the dosing interval.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | 429.9 nanogram per milliliter | Geometric Coefficient of Variation 23 |
Secondary
Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979
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.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 | 2.332 ratio | Geometric Coefficient of Variation 7 |
Secondary
Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979
Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1.
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 | 2.814 ratio | Geometric Coefficient of Variation 3 |
Secondary
Part C: Peak-to-Trough Ratio of PF-06751979
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.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Peak-to-Trough Ratio of PF-06751979 | 2.045 ratio | Geometric Coefficient of Variation 10 |
Secondary
Part C: Plasma Decay Half-Life (t1/2) of PF-06751979
Plasma decay half-life was the time duration for the plasma concentration to decrease by one-half of its original concentration.
Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 | 40.76 hours | Standard Deviation 3.9042 |
Secondary
Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time frame: 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
Population: PK parameter analysis set included all enrolled participants who had at least 1 dose of PF-06751979 and at least of the PK parameters of interest measured.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 4.00 hours | Full Range 24 |
| Part A: Placebo | Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 4.00 hours | — |