A Single Dose Study In Japanese And Western Healthy Subjects To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-04991532

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Metabolism Disorders

• Drug: PF-04991532
  Single dose administration of PF-04991532 (100 mg, 300 mg and 750 mg) in tablet formulation under fasted condition.
• Drug: Placebo
  Single dose administration of matching placebo in tablet formulation at the fasted state
• Drug: PF-04991532
  Single dose administration of PF-04991532 (300 mg and 750 mg) in tablet formulation under fasted condition.

• Experimental: Japanese cohort
  A total of 12 Japanese healthy subjects will be allocated to receive 3 ascending single doses (100 mg, 300 mg and 750 mg) of PF-04991532 or placebo through 3 dosing periods in a randomization ratio of 3:1.
  Interventions:

  • Drug: PF-04991532
  • Drug: Placebo
• Experimental: Weterner Cohort
  9 western healthy subjects will be enrolled to receive 2 single ascending doses (300 mg and 750 mg) of PF-04991532 through 2 dosing periods.
  Intervention: Drug: PF-04991532

Inclusion Criteria:

• Healthy male and/or female subjects of non-childbearing potential, between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests).
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight > 50 kg (110 lbs).
• Japanese subjects must have four Japanese grandparents who were born in Japan.
• Mean body weight and the body weight range of Western subjects must be within ±10% of the Japanese subjects.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Screening supine blood pressure >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), on a single measurement (confirmed by a single repeat, if necessary) following at least 5 minutes of rest.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
• 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
• Pregnant or nursing females or women of childbearing potential.