Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes

• Status: Completed
• Trial end date: 2008-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the safety and effectiveness of rosiglitazone against a sulfonylurea in reducing or slowing the development of atherosclerosis in the blood vessels of the heart.

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

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Glipizide; Hypoglycemic Agents; Maleic acid; Rosiglitazone

Criteria

Inclusion criteria:

• Male or female between 30 to 80 years of age, inclusive.

• Established diagnosis of T2DM (based on diagnostic criteria of the American Diabetes Association (ADA), WHO guidelines or local national guidelines).

• Subjects who are undergoing coronary angiography for evaluation of suspected or previously diagnosed coronary artery disease or who are undergoing PCI.

• Subjects' prior anti-hyperglycemic diabetic therapy:

Diet and exercise only (drug naïve), with HbA1c >7.0 and £ 10.0%. HbA1c > 6.5 and <= 8.5%.

• Left ventricular ejection fraction (EF) ³ 40% as assessed by contrast ventriculography (or previously documented in medical notes within one month prior to index procedure by other methods e.g. echocardiography or nuclear study)

• Female subjects must be postmenopausal (i.e., >6 months without menstrual period), surgically sterile, or using effective contraceptive measures (oral contraceptives, Norplant, Depo-Provera, an intra-uterine device (IUD), a diaphragm with spermicide or a condom with spermicide). Women of childbearing potential must use effective contraceptive measures for at least 1 month prior to visit 1a, and should continue to use the same contraceptive method during the study and for 30 days after discontinuing study medication.

• Willingness and ability to give informed consent prior to entering the study and available to complete the study.

Exclusion Criteria:

• Type 1 diabetes and/or history of diabetic ketoacidosis.

• Exposure to a TZD or other PPAR-g agonist within the 6 months prior to screening visit.

• Subjects treated with triple OAD therapy or high dose dual combination OAD therapy [1].

• Subjects who have required chronic insulin use in the last 6 months (except during pregnancy or acute episodes such as hospitalization, trauma or infection).

• ST segment elevation myocardial infarction in the last 30 days.

• Subjects who have a history or are scheduled to receive coronary artery bypass graft surgery (CABG), valve repair or replacement, aneurysmectomy or planned major non-cardiac surgery during the study period.

• Subjects who have severe cardiac valvular disease

• Stroke or resuscitated in the past 6 months

• History of congestive heart failure (NYHA class I - IV)

• History of significant hypersensitivity or reaction (e.g., difficulty swallowing, difficulty breathing, tachycardia or skin reaction) to any TZD, SU, biguanide or insulin

• Prior history of severe edema or edema requiring medical treatment.

• Chronic disease requiring chronic or intermittent treatment with oral, intravenous, or injected corticosteroids (use of topical, inhaled, or nasal corticosteroids is permissible).

• Recent history or suspicion of current drug abuse or alcohol abuse within the last 6 months.

• Untreated hypo- or hyperthyroidism

• A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer.

• Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgement of the Investigator, would preclude safe completion of the study.

• Blood pressure: SBP >170 or DBP > 100 mmHg

• Significant anemia (Hemoglobin < 11 g/dL for males and < 10 g/dL for females).

• Significant renal disease manifested by serum creatinine (> 1.5mg/dL for males or > 1.4mg/dL for females), or where the use of metformin is contra-indicated.

• Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 2.5 times upper limit of normal (ULN) or bilirubin >2x ULN).

• History of myopathy or history of elevated creatine kinase (CK) > 3 times upper normal limit.

• Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer).

• Women who are lactating, pregnant or planning to become pregnant during the course of the study.

• Unwillingness or inability to comply with the procedures described in this protocol.