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

May 3, 2011 updated by: Pfizer

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Drug: PF-04287881
500 mg once daily for 10 days
Drug: Placebo
To match 500 mg dose once daily for 10 days
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily for 10 days
Drug: PF-04287881
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg dose once daily for 10 days
Experimental: Cohort 2
Drug: PF-04287881
500 mg once daily for 10 days
Drug: Placebo
To match 500 mg dose once daily for 10 days
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily for 10 days
Drug: PF-04287881
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg dose once daily for 10 days
Experimental: Cohort 3
Drug: PF-04287881
500 mg once daily for 10 days
Drug: Placebo
To match 500 mg dose once daily for 10 days
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily for 10 days
Drug: PF-04287881
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg dose once daily for 10 days
Experimental: Cohort 4 (optional)
If intermediate or repeat dose level is needed; dose will not exceed 1100 mg.
Drug: PF-04287881
500 mg once daily for 10 days
Drug: Placebo
To match 500 mg dose once daily for 10 days
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily for 10 days
Drug: PF-04287881
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg dose once daily for 10 days
Experimental: Cohort 5 (Japanese)
Drug: PF-04287881
500 mg once daily for 10 days
Drug: Placebo
To match 500 mg dose once daily for 10 days
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily for 10 days
Drug: PF-04287881
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg dose once daily for 10 days
Experimental: Cohort 6 (Japanese)
Drug: PF-04287881
500 mg once daily for 10 days
Drug: Placebo
To match 500 mg dose once daily for 10 days
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily for 10 days
Drug: PF-04287881
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: PF-04287881
1100 mg dose once daily for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Standard safety assessments including assessment of AEs, laboratory tests, ECGs, and vital signs.
Time Frame: Screening, Dosing days 1-10, through follow-up
Screening, Dosing days 1-10, through follow-up
The primary pharmacokinetic endpoints to be evaluated for PF-04287881 include Cmax, Tmax, and AUC(0-24) on Day 1 and Day 10.
Time Frame: Day 1 and 10
Day 1 and 10

Secondary Outcome Measures

Outcome Measure
Time Frame
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).
Time Frame: Days 1, 5 and 10
Days 1, 5 and 10
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).
Time Frame: Day 10
Day 10
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.
Time Frame: Days 1 and 10
Days 1 and 10
Plasma samples from Cohort 2 will be used for exploratory investigation of circulating metabolites.
Time Frame: Days 1 and 10
Days 1 and 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

December 3, 2009

First Submitted That Met QC Criteria

December 3, 2009

First Posted (Estimate)

December 4, 2009

Study Record Updates

Last Update Posted (Estimate)

May 4, 2011

Last Update Submitted That Met QC Criteria

May 3, 2011

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B0581002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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