A Study of PF-05175157 in Healthy Volunteers and Type 2 Diabetic Patients

• Drug: PF-05175157 or Placebo
  
  One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once daily for 14 days immediately before breakfast, in healthy volunteers.
• Drug: PF-05175157 or Placebo
  
  One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule twice daily for 14 days, immediately before breakfast and dinner, in healthy volunteers.
• Drug: PF-05175157 or Placebo
  
  One oral dose of PF-05175157 or placebo is administered as a powder-in-capsule once (or twice) daily for 14 days, immediately before breakfast (and dinner), in patients with type 2 diabetes.

• Experimental: 30 mg PF-05175157 or Placebo QD
  
  Intervention: Drug: PF-05175157 or Placebo
• Experimental: 100 mg PF-05175157 or Placebo QD
  
  Planned dose might be modified based on emerging safety and PK data.
  Intervention: Drug: PF-05175157 or Placebo
• Experimental: 200 mg PF-05175157 or Placebo QD
  
  Planned dose might be modified based on emerging safety and PK data.
  Intervention: Drug: PF-05175157 or Placebo
• Experimental: 100 mg PF-05175157 or Placebo BID
  
  Planned dose might be modified based on emerging safety and PK data.
  Intervention: Drug: PF-05175157 or Placebo
• Experimental: xxx mg PF-05175157
  
  Dose will be determined based on results obtained from Arms 1 to 4.
  Intervention: Drug: PF-05175157 or Placebo

Inclusion Criteria:

• Healthy male and/or female subjects 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.
• In addition, subjects must have normal pulmonary function tests and normal ocular examination.
• Body Mass Index (BMI) of 25.5 - 35.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Women must be of non-childbearing potential.
• Subjects with type 2 diabetes: HbA1c ?7.0% and ?10.0% if on metformin only, and ?6.5% and ?9.0% if patient requires to be washed-off an SU or DPP-4i.
• For subjects with type 2 diabetes, due to possible effects on disposition, CYP P450 3A4/5 and 2D6 substrates should not be co-administered with study medications.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic seasonal allergies at time of dosing).
• Evidence or history of any chronic ongoing or current pulmonary disease.
• History of smoking in the past 5 years and a history of smoking more than 10 pack years, or history or evidence of habitual use of other (non smoked) tobacco or nicotine containing products within 3 months of Screening, or positive cotinine test at Screening or Day -3.
• Active ocular disease including infection, glaucoma, seasonal allergies, dry eye symptoms or retinal/optic nerve disease.