Multiple Oral Dose Safety, Tolerability And Pharmacokinetic Study Of PF-04287881 In Healthy Adult Subjects
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Respiratory Tract Infections |
Drug: PF-04287881 Drug: Placebo |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) |
| 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 |
- Standard safety assessments including assessment of AEs, laboratory tests, ECGs, and vital signs. [ Time Frame: Screening, Dosing days 1-10, through follow-up ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Plasma samples from Cohort 2 will be used for exploratory investigation of circulating metabolites. [ Time Frame: Days 1 and 10 ] [ Designated as safety issue: No ]
| Enrollment: | 39 |
| Study Start Date: | December 2009 |
| Study Completion Date: | July 2010 |
| Primary Completion Date: | July 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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
|
| Experimental: Cohort 2 |
Drug: PF-04287881
750 mg once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
|
| Experimental: Cohort 3 |
Drug: PF-04287881
1100 mg once daily for 10 days
Drug: Placebo
To match 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
Optional cohort with dose not greater than 1100 mg
Drug: Placebo
Optional cohort to match dose not greater than 1100 mg
|
| Experimental: Cohort 5 (Japanese) |
Drug: PF-04287881
750 mg dose once daily for 10 days
Drug: Placebo
To match 750 mg dose once daily for 10 days
|
| Experimental: Cohort 6 (Japanese) |
Drug: PF-04287881
1100 mg dose once daily for 10 days
Drug: Placebo
To match 1100 mg dose once daily 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| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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).
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Director, Clinical Trial Disclosure Group, Pfizer, Inc. |
| ClinicalTrials.gov Identifier: | NCT01026545 History of Changes |
| Other Study ID Numbers: | B0581002 |
| Study First Received: | December 3, 2009 |
| Last Updated: | May 3, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Pfizer:
|
safety tolerability pharmacokinetics multiple-dose macrolide |
Additional relevant MeSH terms:
|
Respiratory Tract Infections Infection Respiratory Tract Diseases |
ClinicalTrials.gov processed this record on May 16, 2013