Official Title: “A Double-Blind, Randomized, Comparator-Controlled Study In Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl Versus Glimepiride on the Rate of Progression of Coronary Atherosclerotic Disease as Measured by Intravascular Ultrasound”

The primary purpose of this study is to compare the effect of pioglitazone HCl versus glimepiride on the coronary atheroma volume using IVUS of the coronary arteries after up to 18 months of treatment.

Study Type: Interventional

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

Study Primary Completion Date: November 2007

Subjects with type 2 diabetes requiring angiography will have the IVUS procedure performed at baseline and again following 18 months of treatment. Subjects who meet eligibility criteria will be titrated up to a maximum of 45 mg/day pioglitazone HCl or 4 mg/day glimepiride.

Subjects will make 11 visits to the study center. During study visits, subjects will have weight, and vital signs assessed as well as abdominal and hip girth. Physical exams will be done at baseline, 12 months, and 18 months. ECG will be done at baseline and 18 months. Lab assessments will be done at each visit. Completed blood count, chemistries, urinalysis and markers of atherosclerosis will be drawn at baseline, and months 6, 12 and 18. At each visit, information will be collected regarding adverse events the subject may have experienced and any medications the subject is taking. Compliance with study medication will also be assessed at each visit.

Intervention(s) in this Clinical Trial

• Drug: pioglitazone HCl
  • up to 45 mg pioglitazone HCl, tablet, orally, once daily for 18 months
• Drug: glimepiride
  • up to 4 mg of glimepiride, tablet, orally, once daily for 18 months

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • pioglitazone HCl
• Active Comparator: 2
  • glimepiride

Primary Measures

• Effect of treatment on the nominal change in percent atheroma volume of the identified target coronary artery segment from baseline after 18 months of treatment as measured by intravascular ultrasound (IVUS) imaging of the coronary arteries.
  • Time Frame: 18 Months
    Safety Issue?: Yes

Secondary Measures

• Compare the effect of pioglitazone HCl and glimepiride on the nominal change in total atheroma volume
  • Time Frame: 18 Months
    Safety Issue?: Yes
• Compare the effect of pioglitazone HCl and glimepiride on the occurrence of cardiovascular events as a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke.
  • Time Frame: 18 Months
    Safety Issue?: Yes
• Compare the effect of pioglitazone HCl and glimepiride on the occurrence of cardiovascular events as a composite of cardiovascular mortality, nonfatal MI, nonfatal stroke and coronary revascularization.
  • Time Frame: 18 Months
    Safety Issue?: Yes
• Compare the effect of pioglitazone HCl and glimepiride on the occurrence of carotid endarterectomy/carotid stenting, hospitalization for unstable angina, and hospitalization for congestive heart failure (CHF).
  • Time Frame: 18 Months
    Safety Issue?: Yes

Inclusion Criteria:

• Subjects between the ages of 35 and 85 years, inclusive.
• Subjects with type 2 diabetes and coronary artery disease requiring an angiogram.
• Subjects with HbA1c > 6.0% and <9% if taking antidiabetic medications, or HbA1c > 6.5% and <10% if not taking antidiabetic medication.

Exclusion Criteria:

• Subjects with type 1 diabetes.
• Subjects taking more than three antidiabetic therapies.
• Subjects taking thiazolidinediones (TZDs) currently or within 12 weeks prior to randomization.
• Subjects with New York Heart Association Class III or IV cardiac failure or left ventricular dysfunction (left ventricular ejection fraction <40%).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: 85 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 & Development Center, Inc.  

Information obtained from ClinicalTrials.gov on December 03, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00225277

Study ID Number: 01-01-TL-OPI-516

ClinicalTrials.gov Identifier: NCT00225277

Health Authority: United States: Food and Drug Administration