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

Pfizer46 enrolled

Overview

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

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of PF-06751979 following oral doses in healthy adult and healthy elderly subjects at higher doses than previously administered. Such characteristics will enable the design of future clinical trials in patient population, in the effort to optimize the efficacy of PF-06751979, as well as to establish safety margins in humans. Inclusion of healthy elderly subjects will be optional, but can provide additional safety and tolerability information in the age range of the target population while confirming the PK of PF-06751979 in these subjects for future clinical trials in the Alzheimer's disease patient population. The Primary Objective is to evaluate the safety and tolerability of single and multiple ascending oral doses of PF-06751979 in healthy adult subjects. Secondary Objectives are to characterize the pharmacokinetics of PF-06751979 in: plasma following single and multiple ascending oral dose administration in healthy adult subjects and urine following multiple ascending oral dose administration in healthy adult subjects. An additional secondary objective is to evaluate the effect of multiple oral doses of PF 06751979 on CSF A-beta fragments in healthy adult subjects. This study is divided into three parts: Part A - Single ascending doses (SAD) healthy adult subjects (18-55 years); Part B - Multiple ascending doses (MAD) in healthy adult subjects (18-55 years); Part C - Multiple doses (MD) in healthy elderly subjects (60-85 years). Study Parts may be run in a staggered fashion; Part C of the study may commence after satisfactory review of relevant data from Parts A and B.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy Subjects

Interventions

PF-06751979 single doseDRUG

PF-06751979 administered as a single dose suspension in cross-over fashion. Each subject may receive up to 4 study treatments (placebo and up to 3 doses of PF 06751979). The planned dose levels are 200 mg, 400 mg, 700 mg, 200 mg fed (these doses are subject to change based on emerging data).

Placebo single doseDRUG

Matched Placebo suspension administered as single dose

PF-06751979 multiple ascending doseDRUG

PF-06751979 suspension administered daily for 14 consecutive days to parallel cohorts. The planned dose levels are mg, 100 mg, 200 mg, 340 mg (these are subject to change based on emerging data).

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy female subjects of non childbearing potential and male subjects. * Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 (32 kg/m2 for healthy elderly); and a total body weight \>50 kg (110 lbs) at Screening. * Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study. * Additional criterion for subjects of Japanese descent who may be enrolled in Part B (multiple ascending dose cohorts in healthy subjects): Japanese subjects who have four Japanese grandparents born in Japan. Exclusion Criteria: * Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). * Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. * Unwilling or unable to comply with the Lifestyle Guidelines described in the protocol. * Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study. * Any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Locations (1)

Pfizer Clinical Research Unit

Brussels, Belgium

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 and up to the follow up visit (up to 36 days in Part A, 49 days in Part B and C), that were absent before treatment or that worsened relative to pretreatment state.

Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

Number of Participants With Abnormal Physical Examinations Findings

Full physical examination included head, ears, eyes, nose, mouth, skin, heart, lung, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Abnormality in physical examinations was based on investigator's discretion.

Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

Number of Participants With Abnormal Neurological Examinations Findings

The neurological examination included the assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait. Abnormality in neurological examinations was based on investigator's discretion.

Time frame: Part A: Baseline up to 36 days; Part B and C: Baseline up to 49 days

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

C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome measure, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any non-suicidal self-injurious behavior, at baseline were reported.

Data from ClinicalTrials.gov

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