Multiple Oral Dose Safety, Tolerability And Pharmacokinetic Study Of PF-04287881 In Healthy Adult Subjects

Pfizer

Status and phase: Completed; Phase 1

Conditions: Respiratory Tract Infections

Treatments: Drug: Placebo; Drug: PF-04287881

Study type: Interventional

Funder types: Industry

Identifiers

NCT01026545

B0581002

Details and patient eligibility

About

This study is a randomized, investigator blind, subject blind, sponsor-open, placebo controlled, multiple dose escalating, sequential, parallel cohort study of PF-04287881. Subjects will undergo screening procedures within 28 days prior to dosing. At least 1 day after the Screening visit, eligible subjects who meet the entry criteria will be admitted to the Clinical Research Unit (CRU) and confined in the unit until discharge on Day 15.

Approximately 60 healthy volunteers (20 volunteers of Japanese origin for Cohorts 5 and 6), 18 to 55 years of age, males and females (women of non childbearing potential only) will be enrolled and randomized in a 4:1 ratio to treatment with either PF-04287881 or placebo within each cohort. Each cohort will have a 10 day dosing period and each will consist of 10 subjects (8 active and 2 placebo). In each cohort, each subject will receive a single daily oral dose of either placebo or PF-04287881 under fasted state for 10 days.

Full description

Following a Serious Adverse Event (potential Hy's Law case), a risk-benefit assessment review of all preliminary safety data, and a review by Pfizer's internal hepatic injury advisory panel, it was concluded that PF-04287881 had an unacceptable therapeutic window. The FDA was notified of our intention to discontinue development as of 09April2010.

Enrollment: 39 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule.
• Women of non-childbearing potential only.
• Japanese subjects must have 4 Japanese grandparents who were born in Japan.

Exclusion criteria

• Previous antibiotic use within 14 days prior to dosing.
• Use of antibiotics during hospitalization within 90 days prior to dosing.
• History of hypersensitivity to macrolides or ketolides.
• Presence of clinically significant eye conditions (other than corrective lenses).

Trial design

39 participants in 6 patient groups

Cohort 1

Experimental group

Treatment:

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: PF-04287881

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Cohort 2

Experimental group

Treatment:

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: PF-04287881

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Cohort 3

Experimental group

Treatment:

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: PF-04287881

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Cohort 4 (optional)

Experimental group

Description:

If intermediate or repeat dose level is needed; dose will not exceed 1100 mg.

Treatment:

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: PF-04287881

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Cohort 5 (Japanese)

Experimental group

Treatment:

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: PF-04287881

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Cohort 6 (Japanese)

Experimental group

Treatment:

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881

Drug: PF-04287881

Drug: Placebo

Drug: Placebo

Drug: Placebo

Drug: PF-04287881

Drug: Placebo

Drug: PF-04287881