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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Atherosclerosis

Treatments: Drug: rosiglitazone maleate; Drug: Glipizide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00116831

AVD100521

Details and patient eligibility

About

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.

Enrollment: 672 patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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672 participants in 2 patient groups

Glipizide

Active Comparator group

Description:

oral anti-diabetic medication

Treatment:

Drug: Glipizide

rosiglitazone maleate

Experimental group

Description:

oral anti-diabetic medication

Treatment:

Drug: rosiglitazone maleate