Official Title: “A Randomized, Double-Blind, Comparator-Controlled Study of Pioglitazone HCl vs Glyburide in the Treatment of Patients With Type 2 (Non-Insulin-Dependent) Diabetes Mellitus and Mild Cardiac Disease (NYHA I)”

This study was designed to compare the safety and efficacy of pioglitazone HCl and glyburide in the long-term (52 weeks) treatment of patients with type 2 diabetes mellitus and mild cardiac disease (NYHA I).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

The study consisted of a 2-week Screening followed by a 52-week Double-Blind Treatment Period. After study drug was initiated, treatment was optimized for glucose control (to achieve and maintain a fasting fingerstick blood glucose between 100 and 180 mg/dL, inclusive, or fasting plasma glucose (FPG) between 70 and 140mg/dL, inclusive). Subjects were assessed for safety and efficacy of the treatments at scheduled study visits, and data for assessment of primary and secondary endpoints were collected at the Final Visit.

Intervention(s) in this Clinical Trial

• Drug: Pioglitazone hydrochloride, glyburide

Primary Measures

• Change in walking distance during a standardized 6-minute walk test.
  • Time Frame: Week 52 and Final Visit
    

Secondary Measures

• Mortality and morbidity due to cardiovascular event(s), change in cardiovascular treatment regimen, change in 12-lead electrocardiogram (ventricular heart rate), and change in echocardiographic parameters (left ventricular mass, left ventricular ejection
  • Time Frame: Week 52 and Final Visit
    

Inclusion Criteria:

• Men or women greater or equal to 18 years and less than 80 years of age, diagnosed with type 2 diabetes mellitus.
• Patients who were naïve 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. Patients who were currently taking oral antidiabetic pharmacologic therapy must have been on a stable dose for at least 30 days prior to Visit 1.
• Patients with mild cardiac disease (NYHA I).
• Patients who had participated in dietary counseling.
• HbA1c equal to or higher than 7.5 percent and lower than 12 percent at Screening if naïve to oral antidiabetic pharmacologic therapy or taking metformin monotherapy, or equal to or higher than 6.5 percent and lower than 12 percent if currently taking sulfonylurea monotherapy or taking sulfonylurea/metformin combination therapy.
• Patients on stable therapy for cardiovascular dysfunction, defined as no change in therapy for at least 4 weeks prior to Randomization.

Exclusion Criteria:

• Patients who within the past 30 days were 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.
• Patients intolerant of or did not respond to prior sulfonylurea treatment.
• Patients who were currently taking insulin or had been on continuous insulin therapy for control of their diabetes within 1 month of Screening.
• Patients with type 1 (insulin-dependent) diabetes mellitus or a history of ketoacidosis.
• Pregnant or lactating women.
• Patients with cardiac disease and NYHA functional Class II, III, or IV at Screening, or previous history of Class III or IV.
• Patients who had any of the following within 3 months prior to Visit 1: myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, or documented cerebrovascular accident that, in the investigator's opinion, would warrant exclusion from the study.
• Abdominal, thoracic, or vascular surgery during the 3 months prior to Visit 1 that, in the investigator's opinion, warranted exclusion from the study.
• BMI greater than 48 kg/m2 as calculated by [weight (kg)/height (m)2].
• Patients with anemia having hemoglobin below 10.5 g/dL for men and 10.0 g/dL for women.
• Patients with a triglyceride level above 500 mg/dL.
• Patients with clinical evidence of active liver disease or alanine transaminase (ALT) levels more than 2.5 times the upper limit of normal.
• Serum creatinine above 2.0 mg/dL for men and 1.8 mg/dL for women or urinalysis protein (albumin) excretion levels above 2+ on Combistix or equivalent and on repeat 24-hour results with more than 3 g macroproteinuria (if elevated, may have been rescreened in 1 month).
• Patients with a systolic BP above 160 mm Hg or diastolic BP above 90 mm Hg at
• Screening.
• Patients with symptomatic orthostatic hypotension or systolic BP below 90 mm Hg.
• Patients with severe, advanced peripheral vascular disease (limb-threatening ischemia) or claudication resulting in the inability to walk more than 1 block or to climb 10 stairs without interruption.
• Patients with lower extremity amputation that would prevent the patient from performing the exercise test.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 79 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Takeda Global Research & Development Center, Inc.

Overall Clinical Trial Officials and Contacts

Alfonso Perez, MD Study Director Takeda Global Research and Developmnet Center Inc  

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00521742

Study ID Number: 01-00-TL-OPI-520

ClinicalTrials.gov Identifier: NCT00521742

Health Authority: United States: Food and Drug Administration