This single- and multiple-ascending dose study is the first evaluation of PF-04965842, a Janus kinase1 (JAK1) inhibitor, in humans. The goal is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy Western and Japanese subjects.

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.