Multiple Oral Dose Safety, Tolerability And Pharmacokinetic Study Of PF-04287881 In 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.

• 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 1
  Interventions:

  • Drug: PF-04287881
  • Drug: Placebo
• Experimental: Cohort 2
  Interventions:

  • Drug: PF-04287881
  • Drug: Placebo
• Experimental: Cohort 3
  Interventions:

  • Drug: PF-04287881
  • Drug: Placebo
• Experimental: Cohort 4 (optional)
  If intermediate or repeat dose level is needed; dose will not exceed 1100 mg.
  Interventions:

  • Drug: PF-04287881
  • Drug: Placebo
• Experimental: Cohort 5 (Japanese)
  Interventions:

  • Drug: PF-04287881
  • Drug: Placebo
• Experimental: Cohort 6 (Japanese)
  Interventions:

  • Drug: PF-04287881
  • Drug: Placebo

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).