Official Title: “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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Pharmacodynamics Study

Study Primary Completion Date: January 2009

Intervention(s) in this Clinical Trial

• Drug: prasugrel
  • Oral prasugrel 60-mg loading dose, followed by 6-9 days of oral prasugrel 10-mg/day tablet maintenance dose.
• Drug: Clopidogrel
  • Oral clopidogrel 600-mg loading dose, followed by 6-9 days of oral clopidogrel 150-mg/day tablet maintenance dose.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
• Active Comparator: 2
  • Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.

Primary Measures

• Comparison of Inhibition of Platelet Aggregation (IPA) between the prasugrel and clopidogrel treatment groups assessed by Accumetrics VerifyNowTM P2Y12 Assay.
  • Time Frame: 4 hours post loading dose
    Safety Issue?: Yes

Secondary Measures

• Comparison of IPA assessed by Accumetrics VerifyNowTM P2Y12 Assay between the prasugrel and clopidogrel treatment groups.
  • Time Frame: During the first 24 hours after the loading dose and 24 hours after the last maintenance dose
    Safety Issue?: Yes
• Comparison of Maximum Platelet Aggregation (MPA) between prasugrel and clopidogrel treatment groups as assessed by Light Transmittance Aggregometry (LTA)
  • Time Frame: During the first 24 hours after the loading dose and 24 hours after the last maintenance dose
    Safety Issue?: Yes
• Comparison of inhibition of platelet function between prasugrel and clopidogrel treatment groups as assessed by Vasodilator-associated stimulated phosphoprotein (VASP).
  • Time Frame: During the first 24 hours after the loading dose and 24 hours after the last maintenance dose
    Safety Issue?: Yes
• Comparison of inhibition of platelet function between prasugrel and clopidogrel treatment groups as measured by Thromboelastography (TEG)-platelet mapping.
  • Time Frame: During the first 24 hours after the loading dose and 24 hours after the last maintenance dose
    Safety Issue?: Yes

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 75-325mg/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
• HbA1c > or equal to 10mg/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 kg.
• INR >1.5, platelet count <100,000/mm3, or anemia (hemoglobin <10gm/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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 74 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time (UTC/GMT-5 hours, EST) Study Director Eli Lilly and Company  

Overall Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00642174

Study ID Number: 11241

ClinicalTrials.gov Identifier: NCT00642174

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry