Multiple Dose Escalation Trial Of PF-04308515 In Healthy Volunteers

• Safety and tolerability of multiple doses of PF-04308515 as assessed by adverse event reporting, clinical laboratory results, vital signs, physical examinations and electrocardiograms (ECGs). [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
• Characterization of pharmacokinetic parameters of PF-04308515 after multiples doses which will include: Cmax, Tmax, AUC, CL/F, Vz/F, t1/2. Urinary excretion including AE% and CLr will be assessed at steady state. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
• Change from baseline will be utilized to assess PF-04308515's pharmacodynamic effect on biochemical and metabolic biomarkers after 14 days of dosing. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
• For the tablet pharmacokinetics:Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, t1/2 will be calculated from the PF-04308515 plasma concentration versus time data. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Safety and tolerability of 1 oral dose of a tablet formulation of PF-04308515 as assessed by adverse event reporting, clinical laboratory results, vital signs, physical examinations and electrocardiograms (ECGs). [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics (how the drug effects certain target sites of activity in the body) of escalating doses of oral PF-04308515 in healthy volunteers for 14 days as well as one oral dose of a tablet formulation administered for 1 day.

• Drug: PF-04308515
  PF-04308515 will be provided as an oral solution administered at doses of 3, 10, 30 and 100 mg. If an optional cohort is needed the dose would not exceed the established toxicokinetic exposure limits. Solution will be administered orally once daily for 14 days.
• Drug: Placebo
  Placebo solution will be administered to those volunteers who are randomized to the placebo arm. Placebo solution will be administered orally once daily for 14 days.
• Drug: PF-04308515 Tablet
  Tablet formulation to administer a 20 mg dose will be administered to volunteers in Part 2. The study medication will be administered orally once daily for 1 day.

• Experimental: (Part 1) PF-04308515
  Intervention: Drug: PF-04308515
• Placebo Comparator: (Part 1) Solution Placebo
  Intervention: Drug: Placebo
• Experimental: (Part 2) PF-04308515 Tablet
  Intervention: Drug: PF-04308515 Tablet

Inclusion Criteria:

• Healthy males between 18 and 55 years, inclusive
• Healthy females between 18 and 44 years, inclusive
• Females are required to be surgically sterile

Exclusion Criteria:

• Evidence or history of clinically significant disease
• Post-menopausal women
• History of intolerance or significant adverse effects with glucocorticoid therapy