Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3)

A Pharmacodynamic Comparison of Prasugrel (LY640315) Versus High Dose Clopidogrel in Subjects With Type 2 Diabetes Mellitus and Coronary Artery Disease.

This trial is designed as a phase 2 randomized, double-blind double dummy, active comparator controlled, two-period two-arm crossover study to enroll 40 patients across multiple centers. The study will compare platelet function following a prasugrel loading dose and 1 week of prasugrel maintenance therapy with high-dose clopidogrel loading dose and 1 week of high-dose clopidogrel maintenance therapy in patients with drug treated type 2 diabetes mellitus who have coronary artery disease. Various assays of platelet function will be used in this study. Platelet function will be studied using the following assays: Accumetrics VerifyNowTM P2Y12, Light Transmittance Aggregometry (LTA), Vasodilator-associated stimulated phosphoprotein (VASP), and Thromboelastography (TEG)-platelet mapping.

Inclusion Criteria:

• Type 2 Diabetes Mellitus and on oral or parenteral hypoglycemic therapy for at least 1 month.
• History of Coronary Artery Disease with or without other types of vascular disease (such as peripheral vascular disease).
• Taking Aspirin 75-325 mg/day for at least 1 week prior to randomization.
• Between the ages of 18-74 years old.
• If a woman of child bearing age, must not be pregnant and must agree to use reliable method of birth control during the duration of the study.

Exclusion Criteria:

• Thienopyridine therapy within 30 days or have a defined need for thienopyridine treatment.
• Coronary Artery Bypass Graft (CABG) or Percutaneous Coronary Intervention (PCI) with no stent placed within 30 days.
• Planned coronary revascularization
• Hemoglobin A1c (HbA1c) > or equal to 10 mg/dL within the last 3 months.
• Received fibrolytic therapy <24 hours prior to randomization.
• Received non-fibrin-specific fibrinolytic therapy <48 hours prior to randomization.
• At risk of bleeding.
• History of ischemic stroke, transient ischemic attack (TIA), intercranial neoplasm, arteriovenous malformation, or aneurysm.
• Body weight <60 kilograms (kg).
• International Normalized Ratio (INR) >1.5, platelet count <100,000/mm3, or anemia (hemoglobin <10 gm/dL) within 1 week of study entry.
• Are receiving or will receive oral anticoagulation or antiplatelet treatment therapy.
• Are being treated with daily non-steroidal anti-inflammatory drugs (NSAIDS).
• Are pregnant, breast-feeding or plan to become pregnant.