Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Study Of PF-06291874 As Oral Monotherapy To Treat Adults With Type 2 Diabetes Mellitus

A Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Oral Doses Of Pf-06291874 Given As Monotherapy To Adults With Type 2 Diabetes Mellitus

This study is going to assess the safety and tolerability of PF-06291874 in adults with Type 2 Diabetes Mellitus as monotherapy, to evaluate the significance of overall glycemic control in these subjects.

Inclusion Criteria:

• Male subjects and non-childbearing potential female subjects between the ages of 18 and 70 years old.

• Body Mass Index of 18.0 to 45.4 kg/m2; and a total body weight of >50 kg

• HbA1c value at the screening visit meeting once of the following criteria:

  • Currently taking acceptable oral antiglycemic drug therapy within 6.5 to 9.5%
  • Not currently taking any oral antiglycemic drug therapy within 7 to 10.5%

• Fasting plasma glucose concentrations<270mg/dL at the screening and run-in visit, confirmed by a single repeat, if deemed necessary.

• Subjects must be willing and able to perform self-tests of blood glucose at least 4 times per day, and maintain a diary for the duration of participation in the study; and therefore, subjects must be literate.

Exclusion Criteria:

• History of Type 1 diabetes mellitus or secondary forms of diabetes

• One or more self-reported hypoglycemic episodes of sever intensity within 3 months of screening; or 2 or more self-reported hypoglycemic episodes of severe intensity within the previous 6 months.

• History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attach within 6 months of screening.

• History or evidence of diabetic complications with significant end organ damage, such as

  • Proliferative retinopathy and/or macular edema;
  • Diabetic neuropathy complicated by neuropathic ulcers;

• Screening seated systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg after at least a 5 minute seated rest. If the blood pressure exceeds this limit, the blood pressure may be repeated 2 more times following approximately 2 minutes of rest between measurements and the median of the 3 values should be used to determine subject eligibility;

• Male subjects with partners currently pregnant; or male subjects capable of conceiving children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.