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.

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: PF-06751979 multiple ascending dose; Drug: Placebo single dose; Drug: PF-06751979 single dose; Drug: Placebo multiple ascending dose; Drug: Placebo multiple elderly dose; Drug: PF-06751979 multiple dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT02793232

2016-000325-39 (EudraCT Number)

B8271004

Details and patient eligibility

About

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.

Full description

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

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

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

Enrollment: 46 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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46 participants in 3 patient groups

Single Ascending Dose Crossover

Experimental group

Description:

Single Ascending Dose in 4-way cross-over design (PF-06751979/Placebo).

Treatment:

Drug: Placebo single dose

Drug: PF-06751979 single dose

Multiple Ascending Dose

Experimental group

Description:

Multiple dose administration to Healthy Subjects in parallel cohorts (PF-06751979).

Treatment:

Drug: PF-06751979 multiple ascending dose

Drug: Placebo multiple ascending dose

Multiple Dose Elderly

Experimental group

Description:

Multiple dose administration to Healthy Elderly Subjects (PF-06751979). This cohort is optional.

Treatment:

Drug: Placebo multiple elderly dose

Drug: PF-06751979 multiple dose