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

Pfizer55 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Healthy Subjects

Interventions

PF-06751979 single ascending doseDRUG

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.

Placebo single doseDRUG

Matched Placebo solution/suspension administered as single dose.

PF-06751979 multiple ascending doseDRUG

PF-06751979 (solution/suspension) administered daily for 14 consecutive days to parallel cohorts. The dose levels are 5 mg, 15 mg, 50 mg.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (2)

California Clinical Trials Medical Group, Inc

Glendale, California, United States

Glendale Adventist Medical Center

Glendale, California, United States

Outcomes

Primary Outcomes

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

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

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

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.

Data from ClinicalTrials.gov

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Matched Placebo (solution/suspension)administered daily for 14 consecutive days.

PF-06751979 multiple doseDRUG

PF-06751979 (solution/suspension) administered daily for 14 consecutive days. The dose level is 50 mg.

PF-06751979 multiple doseDRUG

Matched Placebo (suspension/solution) administered daily for 14 consecutive days to parallel cohorts.

Time frame: Baseline

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

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

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

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

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

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

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