First-in-Human Study to Evaluate Safety and Tolerability of Single and Multiple Ascending Doses of Janus Kinase-1 Inhibitor PF-04965842 in Healthy Western and Japanese Subjects

• Drug: PF-04965842
  
  Subjects will receive single doses of 3, 10, 30, 100, 200, 400, or 800 mg of PF-04695842 (solution or suspension) in a dose escalation format.
• Drug: Placebo
  
  Subjects will receive single doses of PF-04695842 matching placebo (solution or suspension) in a dose escalation format.
• Drug: PF-04965842
  
  Subjects will receive doses of 30, 100 or 200 mg (solution or suspension) once daily for 10 days.
• Drug: Placebo
  
  Subjects will receive PF-04965842 matching placebo (solution or suspension) once daily for 10 days.
• Drug: PF-04965842
  
  Subjects will receive doses of 100 or 200 mg (suspension or solution) twice daily for 10 days.
• Drug: Placebo
  
  Subjects will receive PF-04965842 matching placebo doses (suspension or solution) twice daily for 10 days.
• Drug: PF-04965842
  
  Subjects will receive 200 mg dose (suspension or solution) twice daily for 10 days.
• Drug: Placebo
  
  Subjects will receive PF-04965842 matching placebo dose (suspension or solution) twice daily for 10 days.
• Drug: PF-04965842
  
  Subjects will receive 400 mg dose (suspension or solution) once daily for 10 days.
• Drug: Placebo
  
  Subjects will receive PF-04965842 matching placebo dose (suspension or solution) once daily for 10 days.

• Experimental: SAD Cohorts 1-8 Experimental Arm
  
  Intervention: Drug: PF-04965842
• Placebo Comparator: SAD Cohorts 1-8 Placebo Arm
  
  Intervention: Drug: Placebo
• Experimental: MAD Cohorts 3 through 5 Experimental Arm
  
  Intervention: Drug: PF-04965842
• Placebo Comparator: MAD Cohorts 3 through 5 Placebo Arm
  
  Intervention: Drug: Placebo
• Experimental: MAD Cohorts 6 and 7 Experimental Arm
  
  Intervention: Drug: PF-04965842
• Placebo Comparator: MAD Cohorts 6 and 7 Placebo Arm
  
  Intervention: Drug: Placebo
• Experimental: MAD Cohort 8 Experimental Arm
  
  Intervention: Drug: PF-04965842
• Placebo Comparator: MAD Cohort 8 Placebo Arm
  
  Intervention: Drug: Placebo
• Experimental: MAD Cohort 9 Experimental Arm
  
  Intervention: Drug: PF-04965842
• Placebo Comparator: MAD Cohort 9 Placebo Arm
  
  Intervention: Drug: Placebo

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive.
• Females must be of non-child bearing potential and either at least 1 year post menopausal (FSH ?40 IU/L), or have documented hysterectomy (with or without bilateral oophrectomy) at least 6 months prior to study day
• Subjects willing to defer receiving prophylactic immunizations (e.g. influenza or pneumococcal vaccines) during the study.
• Absolute lymphocyte count must be greater than or equal to the lower limit of the laboratory reference range.
• Subjects enrolled in Cohort 8 must have four Japanese grandparents born in Japan.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, , pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• History of hepatitis or positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBc Ab) or hepatitis C antibodies (HCV).
• Clinically significant abnormality on chest X-ray performed at screening or within 3 months of screening date; or history of tuberculosis or active or latent or inadequately treated infection.