Clinical trial NCT01026545: Multiple Oral Dose Safety, Tolerability And Pharmacokinetic Study Of PF-04287881 In Healthy Adult Subjects
Official title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-04287881 After Administration Of Multiple Escalating Oral Doses To Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Tract Infections
Keywords: safety
tolerability
pharmacokinetics
multiple-dose
macrolide
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-12-04
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Standard safety assessments including assessment of AEs, laboratory tests, ECGs, and vital signs.
timeFrame: Screening, Dosing days 1-10, through follow-up
measure: The primary pharmacokinetic endpoints to be evaluated for PF-04287881 include Cmax, Tmax, and AUC(0-24) on Day 1 and Day 10.
timeFrame: Day 1 and 10
Secondary outcomes:
measure: Secondary parameters include AUCinf and t1/2 as data permit, apparent oral clearance (CL/F), apparent volume of distribution (Vz/F) and accumulation ratio (Rac).
timeFrame: Days 1, 5 and 10
measure: Urine concentrations of PF 04287881 in Cohorts 2 and 5 will be used to determine total amount excreted (Ae), %Ae relative to dose given and renal clearance (CLR).
timeFrame: Day 10
measure: Concentrations of PF 04287881 will be measured in white blood cell (WBC) polymorphonuclear cells (PMNs) in Cohorts 2 and 5 to determine total exposure in WBC.
timeFrame: Days 1 and 10
measure: Plasma samples from Cohort 2 will be used for exploratory investigation of circulating metabolites.
timeFrame: Days 1 and 10
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: