A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Placebo; PF-04937319
Intervention description: Placebo to match PF-04937319 will be provided.; The initial planned dosing schedule is: 10, 30, 100, 200, and 400 mg, with one cohort to be determined. Doses shown may be adjusted upwards or downwards and may be adjusted to include intermediate doses. All doses will be administered as a single oral dose as a powder-in-capsule (PIC) formulation. PF-04937319 will be supplied as 10 mg and 80 mg (and potentially 1 mg) PIC.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: phase 1; safety and tolerability; PK; PD; type 2 diabetes mellitus; T2DM

Summary:

      The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of PF-04937319 following single escalating oral doses in adult subjects with
      Type 2 Diabetes Mellitus (T2DM).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with type 2 diabetes mellitus who are taking stable doses of metformin only.
             Subjects treated with a sulfonylurea (SU) or a dipeptidyl peptidase-IV inhibitor
             (DPP-IVi) in combination with metformin may be eligible if washed off the SU or
             DPP-IVi to metformin only for a minimum of 4 weeks before dosing.

          -  Male and/or female subjects (females will be women of non childbearing potential)
             between the ages of 18 and 65 years, inclusive, with a body mass index (BMI) of 18.5
             to 45.0 kg/m2 and C-peptide >0.8 ng/mL.

          -  Screening and Day -2 troponin I concentration </=0.05 ng/mL as measured by the Bayer
             Centaur Ultra assay.

          -  HbA1c >/=7% and </=11%. If the patient requires to be washed off an SU or DPP-IVi, the
             HbA1c limits will be >/=7% and </=9.5%.

        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).

          -  Evidence or history of diabetic complications with significant end organ damage, eg,
             proliferative retinopathy and/or macular edema, creatinine clearance </=60 mL/min
             based on the Cockcroft-Gault equation, diabetic neuropathy complicated by neuropathic
             ulcers.

          -  History of stroke, transient ischemic attack, or myocardial infarction within the past
             6 months. Additionally, history of coronary artery bypass graft or stent implantation,
             clinically significant peripheral vascular disease, or congestive heart failure (NYHA
             Classes II-IV). Furthermore, a current history of angina/unstable angina. Also, 12
             lead electrocardiogram (ECG) demonstrating QTc >450 msec at screening, ECG findings
             suggestive of asymptomatic myocardial ischemia, or supine blood pressure >/=160 mm Hg
             (systolic) or </=100 mm Hg (diastolic).

          -  One or more self reported episodes of hypoglycemia within the last 3 months, or two or
             more self reported episodes of hypoglycemia within the last 6 months.

          -  Screening or Day -2 fasting (>/=8 hours) blood glucose, </=70 or >/=270 mg/dL,
             confirmed by a single repeat if deemed necessary.