Multiple Dose Study Of PF-04937319 In Patients With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2; NIDDM
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: PF-04937319; Placebo
Intervention description: Subjects will be dosed with PF-04937319 for 14 days. The doses planned are 10, 30, 100 and 300 mg QD. All doses will be administered as tablets (10 and 100 mg strengths). In each Cohort, 9 patients will receive PF 04937319 and 3 will receive placebo. An additional cohort of 12 patients (9 active, 3 placebo) may be performed to explore a QD or BID dose. The dose for this additional cohort could be a dose already studied or a new dose that is within the exposure stopping criteria.; Placebo to match PF-04937319 will be provided. Subjects will be dosed for 14 days. In each cohort 9 subjects will receive PF-04937319 and 3 will receive placebo.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Pharmacokinetics PK Pharmacodynamics PD T2DM Phase 1 Type 2 diabetes mellitus safety and tolerability

Summary:

      The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK),
      and pharmacodynamics (PD) of PF-04937319 following multiple (14 days) escalating oral doses
      in patients with type 2 diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with type 2 diabetes mellitus who are taking metformin only.

          -  Treatment should be stable, where this is defined as no change in the treatment,
             including dose, over the past 2 months. Regimens may include once daily and twice
             daily dosing only.

          -  Male and/or female patients (females will be women of non childbearing potential)

          -  Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs).

          -  HbA1c between 7.0% and 10.0%.

        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). Patients who have chronic conditions other than
             T2DM (for example, hypercholesterolemia or hypertension) but are controlled by either
             diet or stable (for the last 2 months) doses of medications may be included as well
             (for example, a subject with hypercholesterolemia on appropriate treatment is
             eligible).

          -  Evidence or history of diabetic complications with significant end organ damage, eg,
             proliferative retinopathy and/or macular edema, creatinine clearance less than 60
             mL/min

          -  Any condition possibly affecting drug absorption (eg, gastrectomy)

          -  History of stroke or transient ischemic attack or myocardial infarction within the
             past 6 months

          -  History of coronary artery bypass graft or stent implantation.

          -  Clinically significant peripheral vascular disease (eg, manifested by claudication).

          -  Any history or clinical evidence of congestive heart failure, NYHA Classes II to IV.

          -  One or more self reported significant/severe/requiring treatment episodes of
             hypoglycemia within the last 3 months, or two or more self reported
             significant/severe/requiring treatment episodes of hypoglycaemia within the last 6
             months.

          -  Current history of angina/unstable angina.

          -  Milk or soy allergy