A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: PF-06291874; Placebo
Intervention description: study drug to be given as an oral tablet at 30, 60 or 100 mg; oral tablet
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 206.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether PF-06291874 is effective in the treatment
      T2DM
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males or non-childbearing potential females between the ages of 18 (or the minimum
             country specific age of consent if >18) and 70 years, inclusive, at the screening
             visit (V1) with the diagnosis of T2DM;Female subjects who are not of childbearing
             potential

          2. Subjects who have been on a stable dose of metformin either alone or in combination
             with one additional acceptable OAD

          3. HbA1c at the Screen Visit (V1), as assessed by study specific central laboratory, is
             7-11% if on metformin monotherapy; is 6.5-9.5% if on dual combination therapy
             (metformin plus 1)

        Exclusion Criteria:

          1. Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes;

          2. Fasting plasma glucose levels >270 mg/dL (15.0 mmol/L) at the screening and run in
             visit, (as assessed by study specific central laboratory) confirmed by a single
             repeat, if deemed necessary

          3. History of myocardial infarction, unstable angina, arterial revascularization, stroke,
             New York Heart Association Functional Class III IV heart failure, or transient
             ischemic attack within 6 months of screening;

          4. Any medical condition possibly affecting study drug absorption (eg, gastrectomy or any
             area of intestinal resection, active inflammatory bowel disease or pancreatic
             insufficiency

          5. Subjects with a creatinine clearance <60 mL/min as determined by the Cockcroft Gault
             equation (listed below) using serum creatinine measured at screening, confirmed via a
             single repeat, if deemed necessary

          6. Subject with a positive result for hepatitis B surface antigen (HBsAg), hepatitis B
             core antibodies (HBc Ab) or hepatitis C virus (HCV) antibodies

          7. Screening seated systolic blood pressure >160 mm Hg and/or diastolic blood pressure
             >105 mm Hg after at least a 5 minute rest. Blood pressure determined as the mean of
             triplicate measurements collected with approximately 2 minutes of rest between
             measurements

          8. Screening supine 12 lead ECG demonstrating a corrected QT (QTc) >470 msec; or a QRS
             interval >120 msec. If QTc exceeds 470 msec or QRS exceeds 120 msec, the ECG may be
             repeated 2 more times with an interval of 2-4 minutes between each measurement and the
             mean of the 3 values used to determine the subject's eligibility

          9. Subjects with an arm circumference >52 cm measured at the midpoint of the length of
             the upper arm;

         10. History (within the last 6 months) of regular alcohol consumption exceeding 14 drinks
             per week for men and 7 drinks a week for women. (1 drink = 5 ounces of wine (150 mL)
             or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor);

         11. Treatment with thiazolidinediones (TZDs), or subcutaneously administered anti diabetic
             agents (eg, insulin, exenatide, liraglutide, pramlintide) within 6 weeks prior to V1;

         12. Subjects with a known hypersensitivity or intolerance to a glucagon receptor
             antagonist, or known prior participation in a trial involving PF 06291874;