Healthy Subjects
Conditions
Keywords
Alzheimer's disease
Brief summary
The purpose of this study is to evaluate the safety, tolerability, PK and PD of PF-06751979 following oral doses in healthy adult and healthy elderly subjects.
Interventions
DRUGPF-06751979 single ascending dose
PF-06751979 administered as a single dose (solution/suspension) in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF-06751979). The dose levels are 3 mg, 12 mg, 40 mg, 160 mg.
Matched Placebo solution/suspension administered as single dose.
PF-06751979 (solution/suspension) administered daily for 14 consecutive days to parallel cohorts. The dose levels are 5 mg, 15 mg, 50 mg.
Matched Placebo (solution/suspension)administered daily for 14 consecutive days.
PF-06751979 (solution/suspension) administered daily for 14 consecutive days. The dose level is 50 mg.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female subjects of non-childbearing potential between the ages of 18 and 55 years or between the ages of 60 and 85 years, inclusive. * Body Mass Index (BMI) of 17.5 to 32 kg/m2; and a total body weight \>50 kg (110 lbs) at Screening. * Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). * Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. * Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol. * Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study. * Any severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
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 47 days; Part B and C: Baseline up to 29 days | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 47 days in Part A, 29 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Abnormal Physical Examinations Findings | Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days | A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Abnormality in physical examinations was based on investigator's discretion. |
| Number of Participants With Abnormal Neurological Examinations Findings | Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days | The neurological examination included the assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait. Abnormality in neurological examinations was based on investigator's discretion. |
| Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | Baseline | C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of yes) to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at baseline were reported. |
| Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | Day 7 | C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation or any self-injurious behavior, at day 7 were reported. |
| Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | Day 14 | C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation or any self-injurious behavior, at Day 14 were reported. |
| Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | Day 19 | C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation or any self-injurious behavior, at Day 19 were reported. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days | Criteria for clinically significant ECG abnormalities: maximum PR interval \>=300 milliseconds (msec) and maximum PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 msec and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, maximum QRS interval \>=140 msec and a maximum IFB: Pctchg\>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to \<480 msec, 480 msec to \<500 msec or \>=500 msec and a maximum change of \<=30 change \<60 or \>=60 msec from baseline. |
| Number of Participants With Laboratory Abnormalities | Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days | Abnormalities criteria:hematology(hemoglobin; hematocrit; RBC\<0.8\*lower limit of normal \[LLN\]; platelets\<0.5\*LLN,\>1.75\*upper limit of normal \[ULN\]; WBC\<0.6\*LLN,\>1.5\*ULN; lymphocytes; neutrophils; basophils; eosinophils; monocytes\<0.8\*LLN,\>1.2\*ULN; coagulation(prothrombin (PT); PT ratio\>1.1\*ULN), liver(bilirubin\>1.5\*ULN; aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; gamma GT\>0.3\*ULN; protein; albumin\<0.8\*LLN,\>1.2\*ULN); renal(blood urea nitrogen, creatinine\>1.3\*ULN; uric acid\>1.2\*ULN); electrolytes(sodium\<0.95\*LLN,\>1.05\*ULN; potassium; chloride; calcium; bicarbonate\<0.9\*LLN,\>1.1\*ULN), chemistry(glucose\<0.6\*LLN,\>1.5\* ULN); urinalysis(pH \<4.5,\>8; glucose, ketones, protein, blood, urobilinogen, nitrite, bilirubin, leukocyte, esterase\>1; WBC; bacteria\>=20, epithelial cells\>=6; granular casts, hyaline casts, red cell casts, white cell casts\>1; lipids(cholesterol\[C\], LDL-C\>1.3\*ULN; HDL-C\<0.8\*LLN, triglycerides\>1.3\*ULN); hormones(T4, T3, T4, TSH\<0.8\*LLN,\>1.2\*ULN) |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days | Following parameters were analyzed for examination of vital signs: supine systolic and diastolic blood pressure, pulse rate and body temperature. |
| Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | Day 1 | Continuous cardiac telemetry was conducted in participants. All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern. In this outcome measure, number of participants who had cardiac rhythms of potential clinical concern (based on physician's discretion) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | — |
| Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | AUClast is the area under the plasma concentration time-curve from time zero to the time of last quantifiable concentration. |
| Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | — |
| Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered. |
| Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | AUClast(dn) was calculated by dividing AUClast by the exact dose of PF-06751979 (in mg) administered. |
| Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | AUCinf(dn) was calculated by dividing AUCinf by the exact dose of PF-06751979 (in mg) administered. |
| Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | — |
| Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration. |
| Part A: Apparent Oral Clearance (CL/F) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | Drug clearance is the quantitative measure of the rate at which a drug substance is removed from the blood. |
| Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | — |
| Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14 | Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours. |
| Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | — |
| Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered. |
| Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | — |
| Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14 | Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant. |
| Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant. |
| Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14 | Rac for AUCtau for Day 7 was calculated as: AUCtau on Day 7 divided by AUCtau on Day 1. Rac for AUCtau for Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1. |
| Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | Rac for Cmax for Day 7 was calculated as: Cmax on Day 7 divided by Cmax on Day 1. Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration. |
| Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14 | Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration. |
| Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0-24 hours on Day 14 | Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours. |
| Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0-24 hours on Day 14 | Aetau% was calculated as: 100\*Aetau/dose. Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours. |
| Part B: Renal Clearance of PF-06751979 | 0-24 hours on Day 14 | Renal clearance was calculated as amount of drug excreted unchanged in urine during the dosing interval tau (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours. |
| Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | Baseline, Day 14 | ABeta is the peptide fragment of the amyloid precursor protein. Percent change from baseline in CSF concentration of ABeta fragments (ABeta x-40, ABeta 1-40 and ABeta total) at Day 14 was reported in this outcome measure. |
| Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14 | — |
| Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14 | Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours. |
| Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | — |
| Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered. |
| Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14 | Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant. |
| Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | — |
| Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14 | PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant. |
| Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14 | Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1, where Cmax was the maximum observed plasma concentration. |
| Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14 | Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration. |
| Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 | predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14 | Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration. |
Countries
United States
Participant flow
Pre-assignment details
Study 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- PF-06751979: 3 mg, 12 mg, 40 mg, Placebo Participants received 3 milligram (mg) oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by placebo matched to PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period. | 2 |
| Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by placebo matched to PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period. | 3 |
| Part A- PF-06751979: 3 mg, Placebo, PF-06751979: 40 mg, 160 mg Participants received 3 mg oral solution of PF-06751979 on Day 1 of intervention period 1 followed by placebo matched to PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period. | 2 |
| Part A: Placebo, PF-06751979: 12 mg, 40 mg, 160 mg Participants received placebo matched to PF-06751979 on Day 1 of intervention period 1 followed by 12 mg oral suspension of PF-06751979 on Day 1 of intervention period 2 followed by 40 mg oral suspension of PF-06751979 on Day 1 of intervention period 3 followed by 160 mg oral suspension of PF-06751979 on Day 1 of intervention period 4. After completion of period 4, participants were followed for 10 days. A washout period of at least 7 days was maintained between each intervention period. | 2 |
| Part B- Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29. | 8 |
| Part B- PF-06751979 5 mg Participants received PF-06751979 5 mg oral solution once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29. | 8 |
| Part B- PF-06751979 15 mg Participants received PF-06751979 15 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29. | 8 |
| Part B: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29. | 8 |
| Part C: Placebo Participants received placebo matched to PF-06751979 once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29. | 4 |
| Part C: PF-06751979 50 mg Participants received PF-06751979 50 mg oral suspension once daily from Day 1 up to Day 14 in intervention period of 19 days. Participants were followed up to Day 29. | 10 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1-Part A:4 Days; Part B,C:19 Days | Investigator's Discretion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Period 1-Part A:4 Days; Part B,C:19 Days | Randomized, not treated | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1-Part A:4 Days; Part B,C:19 Days | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A- PF-06751979: 3 mg, 12 mg, 40 mg, Placebo | Part A- PF-06751979: 3 mg, 12 mg, Placebo, PF-06751979 160 mg | Part A- PF-06751979: 3 mg, Placebo, PF-06751979: 40 mg, 160 mg | Part A: Placebo, PF-06751979: 12 mg, 40 mg, 160 mg | Part B- Placebo | Part B- PF-06751979 5 mg | Part B- PF-06751979 15 mg | Part B: PF-06751979 50 mg | Part C: Placebo | Part C: PF-06751979 50 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 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 | 0 Participants | 3 Participants | 9 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 1 Participants | 1 Participants | 43 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 1 Participants | 4 Participants | 46 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 | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 1 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 8 | 1 / 8 | 2 / 8 | 1 / 8 | 3 / 4 | 7 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 4 | 0 / 10 |
Outcome results
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 47 days, Part B and C: Baseline up to 29 days
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 3 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part A: PF-06751979 160 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part B: Placebo | Number of Participants With Abnormal Neurological Examinations Findings | 2 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Abnormal Neurological Examinations Findings | 0 participants |
| Part B: PF-06751979 50 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 50 mg | Number of Participants With Abnormal Neurological Examinations Findings | 2 participants |
Primary
Number of Participants With Abnormal Physical Examinations Findings
A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Abnormality in physical examinations was based on investigator's discretion.
Time frame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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 | 0 participants |
| Part A: PF-06751979 3 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part A: PF-06751979 160 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part B: Placebo | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part B: PF-06751979 50 mg | Number of Participants With Abnormal Physical Examinations Findings | 3 participants |
| Part C: Placebo | Number of Participants With Abnormal Physical Examinations Findings | 0 participants |
| Part C: PF-06751979 50 mg | Number of Participants With Abnormal Physical Examinations Findings | 1 participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Following parameters were analyzed for examination of vital signs: supine systolic and diastolic blood pressure, pulse rate and body temperature.
Time frame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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 Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part A: PF-06751979 3 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part A: PF-06751979 160 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part B: PF-06751979 50 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part C: Placebo | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
| Part C: PF-06751979 50 mg | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | 0 participants |
Primary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Criteria for clinically significant ECG abnormalities: maximum PR interval \>=300 milliseconds (msec) and maximum PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 msec and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, maximum QRS interval \>=140 msec and a maximum IFB: Pctchg\>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to \<480 msec, 480 msec to \<500 msec or \>=500 msec and a maximum change of \<=30 change \<60 or \>=60 msec from baseline.
Time frame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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 Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part A: PF-06751979 3 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part A: PF-06751979 160 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part B: Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part B: PF-06751979 50 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part C: Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 participants |
| Part C: PF-06751979 50 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 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 (PT); PT ratio\>1.1\*ULN), liver(bilirubin\>1.5\*ULN; aspartate aminotransferase; alanine aminotransferase; alkaline phosphatase; gamma GT\>0.3\*ULN; protein; albumin\<0.8\*LLN,\>1.2\*ULN); renal(blood urea nitrogen, creatinine\>1.3\*ULN; uric acid\>1.2\*ULN); electrolytes(sodium\<0.95\*LLN,\>1.05\*ULN; potassium; chloride; calcium; bicarbonate\<0.9\*LLN,\>1.1\*ULN), chemistry(glucose\<0.6\*LLN,\>1.5\* ULN); urinalysis(pH \<4.5,\>8; glucose, ketones, protein, blood, urobilinogen, nitrite, bilirubin, leukocyte, esterase\>1; WBC; bacteria\>=20, epithelial cells\>=6; granular casts, hyaline casts, red cell casts, white cell casts\>1; lipids(cholesterol\[C\], LDL-C\>1.3\*ULN; HDL-C\<0.8\*LLN, triglycerides\>1.3\*ULN); hormones(T4, T3, T4, TSH\<0.8\*LLN,\>1.2\*ULN)
Time frame: Part A: Baseline up to 47 days, Part B and C: Baseline up to 29 days
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 | 0 participants |
| Part A: PF-06751979 3 mg | Number of Participants With Laboratory Abnormalities | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Laboratory Abnormalities | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Laboratory Abnormalities | 1 participants |
| Part A: PF-06751979 160 mg | Number of Participants With Laboratory Abnormalities | 1 participants |
| Part B: Placebo | Number of Participants With Laboratory Abnormalities | 6 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Laboratory Abnormalities | 6 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Laboratory Abnormalities | 4 participants |
| Part B: PF-06751979 50 mg | Number of Participants With Laboratory Abnormalities | 3 participants |
| Part C: Placebo | Number of Participants With Laboratory Abnormalities | 3 participants |
| Part C: PF-06751979 50 mg | Number of Participants With Laboratory Abnormalities | 6 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 up to the follow up visit (up to 47 days in Part A, 29 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Part A: Baseline up to 47 days; Part B and C: Baseline up to 29 days
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 | 0 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 3 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 participants |
| Part A: PF-06751979 3 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| Part A: PF-06751979 12 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| Part A: PF-06751979 40 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part A: PF-06751979 160 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| Part A: PF-06751979 160 mg | 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) | SAEs | 0 participants |
| Part B: Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part B- PF-06751979 5 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 participants |
| Part B- PF-06751979 15 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Part B: PF-06751979 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 participants |
| Part B: PF-06751979 50 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 | 3 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 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 7 participants |
| Part C: PF-06751979 50 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry
Continuous cardiac telemetry was conducted in participants. All abnormal cardiac rhythms were recorded and reviewed by the study physician for the presence of rhythms of potential clinical concern. In this outcome measure, number of participants who had cardiac rhythms of potential clinical concern (based on physician's discretion) were reported.
Time frame: Day 1
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 3 mg | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 12 mg | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 40 mg | Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry | 0 participants |
| Part A: PF-06751979 160 mg | 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 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 Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 3 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 12 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 40 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part A: PF-06751979 160 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
| Part B: Placebo | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation or any self-injurious behavior, at Day 14 were reported.
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 Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 participants |
| Part A: PF-06751979 3 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 participants |
| Part A: PF-06751979 12 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 participants |
| Part A: PF-06751979 40 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 participants |
| Part A: PF-06751979 160 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 participants |
| Part B: Placebo | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19
C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation or any self-injurious behavior, at Day 19 were reported.
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 Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | 0 participants |
| Part A: PF-06751979 3 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | 0 participants |
| Part A: PF-06751979 12 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | 0 participants |
| Part A: PF-06751979 40 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | 0 participants |
| Part A: PF-06751979 160 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | 0 participants |
| Part B: Placebo | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 19 | 0 participants |
Primary
Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of Yes on actual attempt); preparatory acts toward imminent suicidal behavior (Yes on preparatory acts or behavior, aborted attempt or interrupted attempt), suicidal ideation (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation or any self-injurious behavior, at day 7 were reported.
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 Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 participants |
| Part A: PF-06751979 3 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 participants |
| Part A: PF-06751979 12 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 participants |
| Part A: PF-06751979 40 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 participants |
| Part A: PF-06751979 160 mg | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 participants |
| Part B: Placebo | Part B and C: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 participants |
Secondary
Part A: Apparent Oral Clearance (CL/F) of PF-06751979
Drug clearance is the quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Apparent Oral Clearance (CL/F) of PF-06751979 | 172.3 milliliter per minute | Geometric Coefficient of Variation 8 |
| Part A: PF-06751979 3 mg | Part A: Apparent Oral Clearance (CL/F) of PF-06751979 | 175.0 milliliter per minute | Geometric Coefficient of Variation 25 |
| Part A: PF-06751979 12 mg | Part A: Apparent Oral Clearance (CL/F) of PF-06751979 | 213.4 milliliter per minute | Geometric Coefficient of Variation 25 |
| Part A: PF-06751979 40 mg | Part A: Apparent Oral Clearance (CL/F) of PF-06751979 | 156.3 milliliter per minute | Geometric Coefficient of Variation 18 |
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 plasma concentration of a drug.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 436.8 Liter | Geometric Coefficient of Variation 6 |
| Part A: PF-06751979 3 mg | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 494.8 Liter | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 12 mg | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 591.4 Liter | Geometric Coefficient of Variation 26 |
| Part A: PF-06751979 40 mg | Part A: Apparent Volume of Distribution (Vz/F) of PF-06751979 | 523.3 Liter | Geometric Coefficient of Variation 25 |
Secondary
Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979
AUClast is the area under the plasma concentration time-curve from time zero to the time of last quantifiable concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.
| Arm | 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 | 258.6 nanogram*hour per milliliter | Geometric Coefficient of Variation 16 |
| Part A: PF-06751979 3 mg | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 1015 nanogram*hour per milliliter | Geometric Coefficient of Variation 29 |
| Part A: PF-06751979 12 mg | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 2782 nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
| Part A: PF-06751979 40 mg | Part A: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-06751979 | 16890 nanogram*hour per milliliter | Geometric Coefficient of Variation 18 |
Secondary
Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: PK parameter population: all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed'= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 289.7 nanogram*hour per milliliter | Geometric Coefficient of Variation 8 |
| Part A: PF-06751979 3 mg | Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 1142 nanogram*hour per milliliter | Geometric Coefficient of Variation 25 |
| Part A: PF-06751979 12 mg | Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 3121 nanogram*hour per milliliter | Geometric Coefficient of Variation 25 |
| Part A: PF-06751979 40 mg | Part A: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06751979 | 17050 nanogram*hour per milliliter | Geometric Coefficient of Variation 18 |
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.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: PK parameter population: all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.
| Arm | 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 | 86.25 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 16 |
| Part A: PF-06751979 3 mg | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979 | 84.56 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 29 |
| Part A: PF-06751979 12 mg | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979 | 69.53 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 28 |
| Part A: PF-06751979 40 mg | Part A: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Dn) of PF-06751979 | 105.5 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 18 |
Secondary
Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 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.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: PK parameter population: all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed'= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part B and C, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979 | 96.51 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 8 |
| Part A: PF-06751979 3 mg | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979 | 95.10 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 25 |
| Part A: PF-06751979 12 mg | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979 | 77.92 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 25 |
| Part A: PF-06751979 40 mg | Part A: Dose Normalized Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)(Dn) of PF-06751979 | 106.6 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 18 |
Secondary
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979
Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979 | 2.804 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 3 mg | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979 | 2.280 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 35 |
| Part A: PF-06751979 12 mg | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979 | 1.967 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 30 |
| Part A: PF-06751979 40 mg | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(dn) of PF-06751979 | 3.318 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 41 |
Secondary
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The pharmacokinetic (PK) parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 8.411 nanogram per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 3 mg | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 27.36 nanogram per milliliter | Geometric Coefficient of Variation 36 |
| Part A: PF-06751979 12 mg | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 78.66 nanogram per milliliter | Geometric Coefficient of Variation 30 |
| Part A: PF-06751979 40 mg | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | 530.8 nanogram per milliliter | Geometric Coefficient of Variation 41 |
Secondary
Part A: Plasma Decay Half-Life (t1/2) of PF-06751979
Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 29.30 hours | Standard Deviation 0.6 |
| Part A: PF-06751979 3 mg | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 32.94 hours | Standard Deviation 4.9176 |
| Part A: PF-06751979 12 mg | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 32.12 hours | Standard Deviation 3.6403 |
| Part A: PF-06751979 40 mg | Part A: Plasma Decay Half-Life (t1/2) of PF-06751979 | 39.33 hours | Standard Deviation 8.1997 |
Secondary
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, 36, 48 and 72 hours post dose on Day 1
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 4.03 hours | Full Range 8 |
| Part A: PF-06751979 3 mg | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 4.11 hours | Full Range 25 |
| Part A: PF-06751979 12 mg | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 4.08 hours | Full Range 25 |
| Part A: PF-06751979 40 mg | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | 3.03 hours | Full Range 18 |
Secondary
Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Aetau is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.
Time frame: 0-24 hours on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.5090 milligram | Geometric Coefficient of Variation 37 |
| Part A: PF-06751979 3 mg | Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 1.078 milligram | Geometric Coefficient of Variation 54 |
| Part A: PF-06751979 12 mg | Part B: Amount of PF-06751979 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 4.193 milligram | Geometric Coefficient of Variation 37 |
Secondary
Part B: Apparent Oral Clearance (CL/F) of PF-06751979
Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | Day 7 | 210.8 milliliter per minute | Geometric Coefficient of Variation 20 |
| Part A: Placebo | Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | Day 14 | 197.1 milliliter per minute | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 3 mg | Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | Day 7 | 217.8 milliliter per minute | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 mg | Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | Day 14 | 216.9 milliliter per minute | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 12 mg | Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | Day 7 | 199.2 milliliter per minute | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 12 mg | Part B: Apparent Oral Clearance (CL/F) of PF-06751979 | Day 14 | 196.9 milliliter per minute | Geometric Coefficient of Variation 24 |
Secondary
Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 | 628.7 Liter | Geometric Coefficient of Variation 18 |
| Part A: PF-06751979 3 mg | Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 | 573.2 Liter | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 12 mg | Part B: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 | 629.0 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 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | 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 7 | 395.2 nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
| Part A: Placebo | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 1 | 167.7 nanogram*hour per milliliter | Geometric Coefficient of Variation 18 |
| Part A: Placebo | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 422.2 nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 3 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 7 | 1149 nanogram*hour per milliliter | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 1 | 478.8 nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 3 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 1152 nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| Part A: PF-06751979 12 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 1 | 1739 nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 12 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 4236 nanogram*hour per milliliter | Geometric Coefficient of Variation 24 |
| Part A: PF-06751979 12 mg | Part B: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 7 | 4181 nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
Secondary
Part B: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | 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 7 | 79.04 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 20 |
| 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 | 33.56 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 18 |
| 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 | 84.42 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 3 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 | 76.56 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 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 | 31.94 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 20 |
| Part A: PF-06751979 3 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 | 76.78 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 12 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 | 34.79 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 13 |
| Part A: PF-06751979 12 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 | 84.69 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 24 |
| Part A: PF-06751979 12 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 | 83.63 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 20 |
Secondary
Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 7 | 4.137 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 22 |
| Part A: Placebo | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 1 | 2.024 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 22 |
| Part A: Placebo | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 14 | 4.482 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 23 |
| Part A: PF-06751979 3 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 7 | 4.291 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 1 | 1.926 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 22 |
| Part A: PF-06751979 3 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 14 | 4.307 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 12 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 1 | 2.410 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 12 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 14 | 4.915 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 21 |
| Part A: PF-06751979 12 mg | Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 7 | 4.821 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 20 |
Secondary
Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 7 | 20.68 nanogram per milliliter | Geometric Coefficient of Variation 22 |
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 10.12 nanogram per milliliter | Geometric Coefficient of Variation 22 |
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 22.41 nanogram per milliliter | Geometric Coefficient of Variation 23 |
| Part A: PF-06751979 3 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 7 | 64.34 nanogram per milliliter | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 28.90 nanogram per milliliter | Geometric Coefficient of Variation 22 |
| Part A: PF-06751979 3 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 64.63 nanogram per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 12 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 120.6 nanogram per milliliter | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 12 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 245.7 nanogram per milliliter | Geometric Coefficient of Variation 21 |
| Part A: PF-06751979 12 mg | Part B: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 7 | 241.1 nanogram per milliliter | Geometric Coefficient of Variation 20 |
Secondary
Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 7 | 11.30 nanogram per milliliter | Geometric Coefficient of Variation 22 |
| Part A: Placebo | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 14 | 12.55 nanogram per milliliter | Geometric Coefficient of Variation 22 |
| Part A: PF-06751979 3 mg | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 7 | 32.09 nanogram per milliliter | Geometric Coefficient of Variation 11 |
| Part A: PF-06751979 3 mg | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 14 | 32.75 nanogram per milliliter | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 12 mg | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 7 | 125.9 nanogram per milliliter | Geometric Coefficient of Variation 19 |
| Part A: PF-06751979 12 mg | Part B: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 | Day 14 | 120.4 nanogram per milliliter | Geometric Coefficient of Variation 25 |
Secondary
Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14
Rac for Cmax for Day 7 was calculated as: Cmax on Day 7 divided by Cmax on Day 1. Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | Day 7 | 2.044 ratio | Geometric Coefficient of Variation 21 |
| Part A: Placebo | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | Day 14 | 2.213 ratio | Geometric Coefficient of Variation 17 |
| Part A: PF-06751979 3 mg | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | Day 7 | 2.225 ratio | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 3 mg | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | Day 14 | 2.236 ratio | Geometric Coefficient of Variation 16 |
| Part A: PF-06751979 12 mg | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | Day 7 | 2.000 ratio | Geometric Coefficient of Variation 24 |
| Part A: PF-06751979 12 mg | Part B: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF-06751979 at Day 7, 14 | Day 14 | 2.038 ratio | Geometric Coefficient of Variation 23 |
Secondary
Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 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.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | Day 7 | 2.355 ratio | Geometric Coefficient of Variation 15 |
| Part A: Placebo | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | Day 14 | 2.519 ratio | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 mg | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | Day 7 | 2.400 ratio | Geometric Coefficient of Variation 12 |
| Part A: PF-06751979 3 mg | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | Day 14 | 2.406 ratio | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 12 mg | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | Day 7 | 2.403 ratio | Geometric Coefficient of Variation 14 |
| Part A: PF-06751979 12 mg | Part B: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 7, 14 | Day 14 | 2.434 ratio | Geometric Coefficient of Variation 15 |
Secondary
Part B: Peak-to-Trough Ratio (PTR) of PF-06751979
PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | Day 7 | 1.830 ratio | Geometric Coefficient of Variation 8 |
| Part A: Placebo | Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | Day 14 | 1.787 ratio | Geometric Coefficient of Variation 10 |
| Part A: PF-06751979 3 mg | Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | Day 7 | 2.004 ratio | Geometric Coefficient of Variation 6 |
| Part A: PF-06751979 3 mg | Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | Day 14 | 1.973 ratio | Geometric Coefficient of Variation 6 |
| Part A: PF-06751979 12 mg | Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | Day 7 | 1.914 ratio | Geometric Coefficient of Variation 10 |
| Part A: PF-06751979 12 mg | Part B: Peak-to-Trough Ratio (PTR) of PF-06751979 | Day 14 | 2.043 ratio | Geometric Coefficient of Variation 10 |
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 is the amount of drug excreted unchanged in urine during the dosing interval (tau), where dosing interval was 24 hours.
Time frame: 0-24 hours on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.
| Arm | 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%) | 10.18 Percentage of dose excreted | Geometric Coefficient of Variation 37 |
| Part A: PF-06751979 3 mg | Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 7.181 Percentage of dose excreted | Geometric Coefficient of Variation 54 |
| Part A: PF-06751979 12 mg | Part B: Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 8.395 Percentage of dose excreted | Geometric Coefficient of Variation 37 |
Secondary
Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14
ABeta is the peptide fragment of the amyloid precursor protein. Percent change from baseline in CSF concentration of ABeta fragments (ABeta x-40, ABeta 1-40 and ABeta total) at Day 14 was reported in this outcome measure.
Time frame: Baseline, Day 14
Population: The pharmacodynamic CSF concentration population was defined as all enrolled and treated participants who had at least 1 measureable CSF ABeta concentration. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta 1-40 | -5.244 percent change | Standard Error 0.0454 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta Total | -0.489 percent change | Standard Error 0.0708 |
| Part A: Placebo | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta x-40 | -4.368 percent change | Standard Error 0.0395 |
| Part A: PF-06751979 3 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta 1-40 | -60.827 percent change | Standard Error 0.0453 |
| Part A: PF-06751979 3 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta Total | -37.680 percent change | Standard Error 0.072 |
| Part A: PF-06751979 3 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta x-40 | -43.154 percent change | Standard Error 0.0394 |
| Part A: PF-06751979 12 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta x-40 | -53.492 percent change | Standard Error 0.0396 |
| Part A: PF-06751979 12 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta 1-40 | -69.703 percent change | Standard Error 0.0473 |
| Part A: PF-06751979 12 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta Total | -45.287 percent change | Standard Error 0.0708 |
| Part A: PF-06751979 40 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta 1-40 | -86.878 percent change | Standard Error 0.0466 |
| Part A: PF-06751979 40 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta Total | -61.984 percent change | Standard Error 0.0722 |
| Part A: PF-06751979 40 mg | Part B: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid Beta (ABeta) Fragments on Day 14 | ABeta x-40 | -61.348 percent change | Standard Error 0.0394 |
Comparison: ABeta 1-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-61.95, -55.08]Mixed Model Repeated Measures
Comparison: ABeta 1-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-70.66, -65.16]Mixed Model Repeated Measures
Comparison: ABeta 1-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-87.26, -84.95]Mixed Model Repeated Measures
Comparison: ABeta x-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-44.7, -36.1]Mixed Model Repeated Measures
Comparison: ABeta x-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-54.78, -47.7]Mixed Model Repeated Measures
Comparison: ABeta x-40: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-62.4, -56.56]Mixed Model Repeated Measures
Comparison: ABeta Total: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-45.06, -28.62]Mixed Model Repeated Measures
Comparison: ABeta Total: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-51.72, -37.38]Mixed Model Repeated Measures
Comparison: ABeta Total: General linear model with intervention, as the fixed effect and loge(baseline) as covariate.p-value: <0.000180% CI: [-66.51, -56.42]Mixed Model Repeated Measures
Secondary
Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 | 37.15 hours | Standard Deviation 5.2041 |
| Part A: PF-06751979 3 mg | Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 | 30.65 hours | Standard Deviation 3.1942 |
| Part A: PF-06751979 12 mg | Part B: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 | 37.36 hours | Standard Deviation 5.9074 |
Secondary
Part B: Renal Clearance of PF-06751979
Renal clearance was calculated as amount of drug excreted unchanged in urine during the dosing interval tau (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time frame: 0-24 hours on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Data for this outcome measure was not planned to be analyzed for Part A and C, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Renal Clearance of PF-06751979 | 20.10 milliliter per minute | Geometric Coefficient of Variation 40 |
| Part A: PF-06751979 3 mg | Part B: Renal Clearance of PF-06751979 | 15.58 milliliter per minute | Geometric Coefficient of Variation 57 |
| Part A: PF-06751979 12 mg | Part B: Renal Clearance of PF-06751979 | 16.51 milliliter per minute | Geometric Coefficient of Variation 48 |
Secondary
Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 7; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 7 | 6.02 hours | Full Range 20 |
| Part A: Placebo | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 3.98 hours | Full Range 18 |
| Part A: Placebo | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 4.01 hours | Full Range 20 |
| Part A: PF-06751979 3 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 7 | 4.02 hours | Full Range 12 |
| Part A: PF-06751979 3 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 4.07 hours | Full Range 20 |
| Part A: PF-06751979 3 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 4.05 hours | Full Range 13 |
| Part A: PF-06751979 12 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 2.99 hours | Full Range 14 |
| Part A: PF-06751979 12 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 3.00 hours | Full Range 24 |
| Part A: PF-06751979 12 mg | Part B: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 7 | 3.83 hours | Full Range 20 |
Secondary
Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Apparent Oral Clearance (CL/F) of PF-06751979 on Day 14 | 184.9 milliliter per minute | Geometric Coefficient of Variation 20 |
Secondary
Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Apparent Volume of Distribution (Vz/F) of PF-06751979 at Day 14 | 637.4 Liter | Geometric Coefficient of Variation 23 |
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 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hour post dose on Day 14
Population: PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies participants who were evaluable at specified time points. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | 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 | 1621 nanogram*hour per milliliter | Geometric Coefficient of Variation 22 |
| Part A: Placebo | Part C: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06751979 | Day 14 | 4505 nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
Secondary
Part C: Dose Normalized Area Under the Curve From Time Zero to End of Dosing Interval Tau (AUCtau)(Dn) of PF-06751979
Dose normalized area under the concentration curve from time 0 to end of dosing interval (AUCtau)(dn), where dosing interval was 24 hours. AUCtau(dn) was calculated by dividing AUCtau by the exact dose of PF-06751979 (in mg) administered to a participant.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post dose on Day 14
Population: PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies participants who were evaluable at specified time points. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | 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 | 32.44 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 22 |
| 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 | 90.10 [nanogram*hour/milliliter]/milligram | Geometric Coefficient of Variation 20 |
Secondary
Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979
Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of PF-06751979 (in mg) administered.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 1 | 2.059 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 25 |
| Part A: Placebo | Part C: Dose Normalized Maximum Observed Plasma Concentration (Cmax)(Dn) of PF-06751979 | Day 14 | 5.129 [nanogram/milliliter]/milligram | Geometric Coefficient of Variation 23 |
Secondary
Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 1 | 102.9 nanogram per milliliter | Geometric Coefficient of Variation 25 |
| Part A: Placebo | Part C: Maximum Observed Plasma Concentration (Cmax) of PF-06751979 | Day 14 | 256.4 nanogram per milliliter | Geometric Coefficient of Variation 23 |
Secondary
Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Minimum Observed Plasma Concentration (Cmin) of PF-06751979 on Day 14 | 135.8 nanogram per milliliter | Geometric Coefficient of Variation 18 |
Secondary
Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14
Rac for Cmax for Day 14 was calculated as: Cmax on Day 14 divided by Cmax on Day 1, where Cmax was the maximum observed plasma concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac Cmax) of PF 06751979 at Day 14 | 2.504 ratio | Geometric Coefficient of Variation 12 |
Secondary
Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14
Rac for AUCtau at Day 14 was calculated as: AUCtau on Day 14 divided by AUCtau on Day 1, where Cmax was the maximum observed plasma concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hour post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Observed Accumulation Ratio (Rac) for AUCtau of PF-06751979 at Day 14 | 2.821 ratio | Geometric Coefficient of Variation 14 |
Secondary
Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14
PTR was calculated by dividing Cmax by Cmin of PF-06751979 administered to a participant.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here,'number of participants analyzed'=participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for Part A, as pre specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Peak-to-Trough Ratio (PTR) of PF-06751979 at Day 14 | 1.887 ratio | Geometric Coefficient of Variation 9 |
Secondary
Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14
Plasma decay half-life is the time measured for the plasma concentration of PF-06751979 to decrease by one half of its original concentration.
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hour post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, 'number of participants analyzed' signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Plasma Decay Half-Life (t1/2) of PF-06751979 at Day 14 | 39.95 hours | Standard Deviation 3.1794 |
Secondary
Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979
Time frame: predose, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post dose on Day 1; predose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96 and 120 hours post dose on Day 14
Population: The PK parameter population included all enrolled participants who had at least 1 dose of PF-06751979 and at least 1 of the PK parameters of interest measured. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 1 | 4.00 hours |
| Part A: Placebo | Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06751979 | Day 14 | 4.00 hours |