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

Respiratory Tract Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01026545
• Other study ID #: B0581002
• Status: Completed
• Phase: Phase 1
• First received: December 3, 2009
• Last updated: May 3, 2011
• Start date: December 2009
• Est. completion date: July 2010

Study information

• Verified date: May 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Respiratory Tract Infections

Intervention

Drug:
• PF-04287881
500 mg once daily for 10 days
• Placebo
To match 500 mg dose once daily for 10 days
• PF-04287881
750 mg once daily for 10 days
• Placebo
To match 750 mg dose once daily for 10 days
• PF-04287881
1100 mg once daily for 10 days
• Placebo
To match 1100 mg dose once daily for 10 days
• PF-04287881
Optional cohort with dose not greater than 1100 mg
• Placebo
Optional cohort to match dose not greater than 1100 mg
• PF-04287881
750 mg dose once daily for 10 days
• Placebo
To match 750 mg dose once daily for 10 days
• PF-04287881
1100 mg dose once daily for 10 days
• Placebo
To match 1100 mg dose once daily for 10 days

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Standard safety assessments including assessment of AEs, laboratory tests, ECGs, and vital signs.		Screening, Dosing days 1-10, through follow-up	Yes
Primary	The primary pharmacokinetic endpoints to be evaluated for PF-04287881 include Cmax, Tmax, and AUC(0-24) on Day 1 and Day 10.		Day 1 and 10	No
Secondary	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).		Days 1, 5 and 10	No
Secondary	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).		Day 10	No
Secondary	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.		Days 1 and 10	No
Secondary	Plasma samples from Cohort 2 will be used for exploratory investigation of circulating metabolites.		Days 1 and 10	No

External Links

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