A 12-week Study To Evaluate PF-06291874 Once a Day in Adults With T2DM Inadequately Controlled On Metformin

Pfizer

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: PF-06291874; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02554877

B4801010

Details and patient eligibility

About

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

Full description

This will be a randomized, double blind, stratified, placebo controlled, parallel group study conducted in T2DM subjects receiving background metformin therapy. Subjects will complete screening procedures to determine eligibility, followed by an 8 week metformin stabilization period prior to randomization. In addition, subjects taking other OADs, in combination with metformin, will undergo a washout during this period, in which non metformin OAD medications will be temporarily discontinued for the duration of the trial. Following confirmation of study eligibility criteria at randomization, subjects will be stratified into 2 groups based on the use of concomitant statin therapy. Each stratum will be randomized across treatment groups, such that the number of subjects taking concomitant statin therapy and those not taking statin therapy will be approximately balanced across treatment groups.

Enrollment: 206 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

206 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

PF-06291874, 30 mg

Experimental group

Treatment:

Drug: PF-06291874

PF-06291874, 60 mg

Experimental group

Treatment:

Drug: PF-06291874

PF-06291874, 100 mg

Experimental group

Treatment:

Drug: PF-06291874