A Study of the Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of PF-05180999 In Healthy Adults

• Drug: PF-05180999
  
  Ascending single oral doses of 120, 240, and 420 mg modified-release tablets
• Drug: Placebo
  
  Placebo tablets
• Drug: 120 mg MR PF-05180999
  
  Single 120 mg dose administered as modified release formulation
• Drug: 360 mg MR PF-05180999
  
  Single 360 mg dose administered as modified release formulation
• Drug: 10 mg cetirizine
  
  Single 10 mg dose of cetirizine

• Experimental: Arm A1
  
  Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999
  Intervention: Drug: PF-05180999
• Placebo Comparator: Arm A2
  
  Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo
  Intervention: Drug: Placebo
• Experimental: Arm B1
  
  Part B of study to assess effects of PF-05180999 on histamine-induced wheal
  Intervention: Drug: 120 mg MR PF-05180999
• Experimental: Arm B2
  
  Part B of study to assess effects of PF-05180999 on histamine-induced wheal
  Intervention: Drug: 360 mg MR PF-05180999
• Experimental: Arm B3
  
  Positive control to ensure histamine-induced wheal assay integrity
  Intervention: Drug: 10 mg cetirizine
• Experimental: Arm B4
  
  Placebo control
  Intervention: Drug: Placebo

Inclusion Criteria:

• Healthy male subjects between the ages of 18 and 55 years
• No history of clinically-relevant atopic or dermatological disease
• Positive reaction to intradermal injection of histamine

Exclusion Criteria:

• Subjects with screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal.
• Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C
• Intolerance to intradermal histamine injection.
• Subjects with dark skin (Part B only).