Effect of Prasugrel on Platelets After One Week in Patients Already Taking Clopidogrel After a Cardiac Event

Study Overview
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Brief Summary
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This study will compare the effect of a prasugrel 10-mg maintenance dose with a clopidogrel 75-mg maintenance dose on platelet activity, approximately 1 week after the first dose of study drug, in subjects who have been taking clopidogrel 75 mg daily following a percutaneous coronary intervention (PCI) with placement of a stent, performed to treat acute coronary syndrome (ACS).

Official Title
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A Pharmacodynamic Comparison of Prasugrel (LY640315) Versus Clopidogrel in Subjects With Acute Coronary Syndrome Who Are Receiving Clopidogrel

Conditions
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Coronary Arteriosclerosis, Acute Coronary Syndrome

Intervention / Treatment
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* Drug: prasugrel 10 mg
* Drug: clopidogrel
* Drug: prasugrel placebo
* Drug: prasugrel 60 mg
* Drug: clopidogrel placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with a recent history of an ACS event based on the disease diagnostic criteria between 30 and 330 days prior to enrollment, and who state that they are supposed to be taking daily aspirin and maintenance dose 75-mg clopidogrel. Are of a legal age (and at least 18 years of age but less than 75 years of age) and competent mental condition to provide written informed consent before entering the study. Exclusion Criteria: Left main coronary artery stent or left anterior descending (LAD) bifurcation stent. Have any form of coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) planned to occur during the study (from signing consent through the final visit). Have undergone CABG or PCI within 30 days of entry into the study. Receiving or will receive oral anticoagulation or other antiplatelet therapy (other than aspirin and clopidogrel) that cannot be safely discontinued for the duration of the study. Receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) that cannot be discontinued or are anticipated to require daily treatment with NSAIDs during the study. Have any of the following: history of ischemic or hemorrhagic stroke intracranial neoplasm, arteriovenous malformation, or aneurysm history of transient ischemic attack (TIA), have a body weight less than 60 kilograms (kg).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prasugrel 10/10 mg<br>Open label (lead-in) dose of clopidogrel 75 milligram (mg) for 10 to 14 days. Upon completion, assignment to a single loading dose of prasugrel 10 mg and placebo, followed by maintenance dose of prasugrel 10 mg taken for 13 to 15 days. | Drug: prasugrel 10 mg<br>* 10 mg tablet taken orally<br>* Other names: Efient;Drug: clopidogrel<br>* 75 mg tablet taken orally<br>* Other names: Clavix;Drug: prasugrel placebo<br>* oral, as blinding mechanism.<br>Drug: clopidogrel placebo<br>* oral, as blinding mechanism<br>|
| Experimental: Clopidogrel 75/75 mg<br>Open label (lead-in) dose of clopidogrel 75 mg for 10 to 14 days. Upon completion, assignment to a single loading dose of clopidogrel 75 mg and placebo, followed by maintenance dose of clopidogrel 75 mg taken for 13 to 15 days. | Drug: clopidogrel<br>* 75 mg tablet taken orally<br>* Other names: Clavix;Drug: prasugrel placebo<br>* oral, as blinding mechanism.<br>|
| Experimental: Prasugrel 60/10 mg<br>Open label (lead-in) dose of clopidogrel 75 mg for 10 to 14 days. Upon completion, assignment to a single loading dose of prasugrel 60 mg and placebo followed by maintenance dose of prasugrel 10 mg taken for 13 to 15 days. | Drug: prasugrel 10 mg<br>* 10 mg tablet taken orally<br>* Other names: Efient;Drug: clopidogrel<br>* 75 mg tablet taken orally<br>* Other names: Clavix;Drug: prasugrel 60 mg<br>* 60 mg (six 10-mg tablets) taken orally<br>* Other names: Efient;Drug: clopidogrel placebo<br>* oral, as blinding mechanism<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Platelet Aggregation (MPA) to 20 Micromolar (uM) Adenosine Diphosphase (ADP) | Maximum platelet aggregation (MPA) to 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA). | 1 week after first dose of randomized study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Platelet Aggregation (MPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | Maximum platelet aggregation (MPA) to 5 and 20 micromolar adenosine diphosphase (ADP) as measured with light transmittance aggregometry (LTA). | 2 hours, 24 hours, 1 week, 2 weeks after first dose of randomized study drug | 
| Maximum Platelet Aggregation (MPA) to 20 uM ADP According to Clopidogrel Use at Time of Qualifying Acute Coronary Syndrome (ACS) Event | Data provided are the MPA to 20 micromolar ADP while taking clopidogrel (measurement taken at end of the 14 day open label phase) grouped by subjects who were taking clopidogrel at the time of the qualifying ACS event compared with subjects who were not taking clopidogrel at the time of the qualifying ACS event. | End of 14 day open label | 
| Residual Platelet Aggregation (RPA) (to 5 and 20 uM ADP) at 2 Hours, 24 Hours, 1 Week and 2 Weeks | Residual platelet aggregation after the addition 5 and 20 micromolar ADP as measured with light transmittance aggregometry (LTA). | 2 hours, 24 hours, 1 week, 2 weeks after first dose of randomized study drug | 
| Correlation Coefficent of Verify Now™ P2Y12 Assay Values to Maximum Platelet Aggregation (MPA) and Residual Platelet Aggregation (RPA) to 20 uM ADP at 1 Week | Correlation Coefficient comparing the Accumetrics VerifyNow™ P2Y12 device with light transmittance aggregometry (LTA) for monitoring platelet aggregation. | 1 week after randomized study drug | 
| Number of Participants With Bleeding Events by Visit According to Thrombolysis in Myocardial Infarction Study Group (TIMI) Criteria | Bleeding events were classified as Major Bleeding, Minor Bleeding, or Insignificant according to TIMI criteria. Major Bleeding: any intracranial hemorrhage OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 gm/dL from baseline. Minor Bleeding: any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in Hgb of ≥3 gm/dL but <5 gm/dL from baseline. Insignificant Bleeding: any bleeding event that does not meet criteria for a Major or Minor Bleed. | End of 14 day open label (baseline); 24 Hours, 7 days, 14 days after first dose of randomized drug |