Multiple Dose Escalation Study In Medically Stable Subjects With Psoriasis

• Psoriasis
• Immunomodulation

• Drug: tofacitinib
  5 mg BID For 13 days and once on Day 14
• Drug: tofacitinib
  10 mg BID for 13 days and once on Day 14*
• Drug: tofacitinib
  20 mg BID for 13 days and once on Day 14
• Drug: tofacitinib
  30 mg BID for 13 days and once on Day 14
• Drug: tofacitinib
  60 mg tablet once a day (QD) for 14 days
• Drug: tofacitinib
  50 mg tablets two times a day (BID) for 13 days and once on day 14

• Experimental: 5 mg BID
  5 mg BID for 13 days and once on Day 14
  Intervention: Drug: tofacitinib
• Experimental: 10 mg BID
  10 mg BID for13 days and once on Day 14*
  Intervention: Drug: tofacitinib
• Experimental: 20 mg BID
  20 mg BID for 13 days and once on Day 14
  Intervention: Drug: tofacitinib
• Experimental: 30 mg BID
  30 mg BID for 13 days and once on Day 14
  Intervention: Drug: tofacitinib
• Experimental: 60 mg QD
  60 mg QD for 14 days
  Intervention: Drug: tofacitinib
• Experimental: 50 mg BID
  50 mg BID x 13 days and once on day 14
  Intervention: Drug: tofacitinib

Inclusion Criteria:

• Male and/or female subjects between the ages of 18 and 65 years, inclusive, with active psoriasis lesion(s).
• Subjects should be healthy with the exception of psoriasis, where healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination. Blood pressure must be < 140/89. Body Mass Index (BMI) between 18-36 kg/m2, inclusive; and a total body weight >50 kg (110 lbs)
• The following laboratory variables must be no more than 10% below the lower limit of the normal reference range: RBC, hemoglobin, hematocrit, WBC, absolute neutrophil count. The absolute lymphocyte count must be greater than or equal to the lower limit of the reference range. Values for AST, ALT, bilirubin and alkaline phosphatase must be no more than 10% above the upper limit of the normal reference range. Values for total cholesterol and LDL must be no more than 20% above the upper limit of the normal reference range except for subjects being treated for hyperlipidemia. Normal glomerular filtration rate (> 80 mL/min).

Exclusion Criteria:

• Subjects with evidence or history of clinically significant hematological, renal, urological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic disorder.
• Subjects with controlled essential hypertension and/or hyperlipidemia may be eligible for the study provided that any medications that are administered.
• Screening 12-lead ECG demonstrating at least one of the following: heart rate > 100 bpm, QRS >120 msec, QTc > 430 msec (males), QTc > 450 msec (females) or PR > 220 msec.
• Abnormal chest radiographs including, but not limited to, evidence of past or present tuberculosis infection. History of tuberculosis without treatment and/or positive tuberculin reaction without known vaccination with BCG.
• Subjects with a history of tumors with the exception of adequately treated basal cell carcinoma of the skin.