A Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Doses Of PF-04937319 In Subjects With Type 2 Diabetes Mellitus

Pfizer

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: PF-04937319; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01044537

B1621001

Details and patient eligibility

About

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).

Full description

The purpose of this phase 1 study is to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF04937319 following single escalating oral doses in adult subjects with T2DM.

Enrollment: 50 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo.

Treatment:

Drug: Placebo

PF-04937319

Experimental group

Description:

In each ascending-dose cohort, approximately 6 subjects will receive active treatment and 3 will receive placebo. There will be approximately 6 dosing levels of PF-04937319

Treatment:

Drug: PF-04937319