Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease

• Status: Completed
• Trial end date: 2003-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the cardiovascular effects of pioglitazone, once daily (QD), versus glyburide when administered to patients with type 2 diabetes mellitus and mild cardiac disease.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Takeda
• Collaborator: Takeda Pharmaceuticals North America, Inc.
• Treatments: Glyburide; Pioglitazone

Criteria

Inclusion Criteria

• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

• Diagnosed with type 2 diabetes mellitus.

• Naive to oral antidiabetic pharmacologic therapy, who were currently taking sulfonylurea monotherapy, who were currently taking sulfonylurea/metformin combination therapy, or who were currently taking metformin monotherapy.

• Mild cardiac disease New York Heart Association functional Class I.

• Participated in dietary counseling.

• Glycosylated hemoglobin greater than or equal to 7.5% and less than 12% at Screening if naïve to oral antidiabetic pharmacologic therapy or taking metformin monotherapy, or greater than or equal to 6.5% and less than 12% if currently taking sulfonylurea monotherapy or taking ulfonylurea/metformin combination therapy.

• Stable therapy for cardiovascular dysfunction, defined as no change in therapy for greater than or equal to 4 weeks prior to Randomization.

Exclusion Criteria:

• Within the past 30 days treated with rosiglitazone, pioglitazone, or troglitazone or those previously treated with rosiglitazone, pioglitazone, or troglitazone but discontinued from therapy because of lack of efficacy or clinical or laboratory signs of intolerance.

• Treated with a sulfonylurea but discontinued for lack of efficacy or clinical or laboratory intolerance.

• Currently taking insulin or on continuous insulin therapy for control of their diabetes

• Type 1 (insulin-dependent) diabetes mellitus or a history of ketoacidosis.

• Any other investigational drug during the 30 days prior to Visit 1 or who will receive such a drug during the time-frame of this study.

• History of chronic alcoholism or drug abuse during the 6 months prior to the study.

• New York Heart Association functional Class II, III, or IV cardiac disease at Screening, or previous history of Class III or IV.

• Any of the following:

• myocardial infarction

• coronary angioplasty or bypass graft

• unstable angina pectoris

• transient ischemic attacks

• documented cerebrovascular accident. 9. Abdominal, thoracic, or vascular surgery during the 3 months prior to Visit 1.

• Planned surgical or catheterization intervention within 6 months following Visit 1.

• Awaiting cardiac transplantation.

• Intercurrent illness severe enough to require hospitalization during the 3 weeks prior to Visit 1.

• Body mass index greater than 48 kg/m2 as calculated by [weight (kg)/height (m)2].

• Anemia having hemoglobin less than 10.5 g per dL for men and 10.0 g per dL for women.

• Triglyceride level greater than 500 mg per dL.

• Clinical evidence of active liver disease or alanine transaminase levels greater than 2.5 times the upper limit of normal.

• Serum creatinine greater than 2.0 mg per dL for men and 1.8 mg per dL for women or urinalysis protein (albumin) excretion levels greater than 2 plus on Combistix or equivalent and on repeat 24-hour results with greater than 3 g macroproteinuria.

• Unstable coronary syndromes.

• Systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg at Screening.

• Serious uncontrolled cardiac rhythm disturbances.

• Symptomatic orthostatic hypotension or systolic blood pressure less than 90 mm Hg.

• Severe, advanced peripheral vascular disease (limb-threatening ischemia) or claudication resulting in the inability to walk greater than 1 block or to climb 10 stairs without interruption.

• Lower extremity amputation that would prevent the patient from performing the exercise test.

• Any other serious disease or condition which might affect life-expectancy or make it difficult to successfully manage and follow the subjects according to the protocol.

• Unexplained clinically significant findings on chest x-ray.

• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

• Oral, injected, or inhaled corticosteroids of greater than 2 week duration, or the need for recurrent us of corticosteroids.

• Prescription niacin

• Anti-diabetic medications except metformin

• Cardiovascular medications must remain stable for at least 4 weeks prior to Randomization

• Non-steroidal anti-inflammatory drugs

• Aspirin greater than 325 mg per day