Overview

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