Prasugrel/Clopidogrel Maintenance Dose Washout Study
Prasugrel/Clopidogrel Maintenance Dose Washout Study
The primary objective of the study is to describe the cumulative proportion of subjects who
 return to baseline platelet P2Y12 receptor function over time (up to 12 days post last
 maintenance dose) following discontinuation of prasugrel 10 mg daily x 7 days assessed by
 Accumetrics VerifyNow P2Y12 reaction units (PRU) and described by Kaplan Meier curves. The
 primary analysis is descriptive and is intended to provide information relating to the return
 of baseline platelet function following discontinuation of maintenance therapy with either
 prasugrel or clopidogrel.
Inclusion Criteria:

 -  Male or female subjects >/= 18 years and <75 years of age

 -  Weight >/= 60 kg

 -  On aspirin therapy (81 mg to 325 mg daily) at the time of screening and able to
 maintain a consistent aspirin dosing regimen from the baseline visit through the final
 study visit

 -  Subjects who do not have contraindications for a thienopyridine (ie, prasugrel,
 clopidogrel or ticlopidine), and have a history of stable atherosclerosis represented
 by Coronary Artery disease, defined as any of the following:

 -  chronic stable angina

 -  Prior history of acute coronary syndrome (>/= 30 days before screening) including
 unstable angina or acute myocardial infarction (ST elevation MI [STEMI] or non-ST
 elevation MI [NSTEMI]), not currently prescribed or currently on thienopyridine
 therapy;

 -  Previous coronary revascularization including percutaneous transluminal coronary
 angioplasty (PTCA), stent, or coronary artery bypass grafting (CABG) coronary
 artery disease (>/= 50% obstruction) in at least one coronary vessel after
 angiography

 -  Female subjects who meet one of the following:

 -  Women of childbearing potential with a negative serum pregnancy test at screening
 who are not breast feeding, do not plan to become pregnant during the study, and
 agree to use an approved method of birth control during the study. Approved
 methods of birth control are oral, path, injectable or implantable hormonal
 contraception, intrauterine device, diaphragm plus spermicide, or female condom
 plus spermicide. Abstinence, partner's use of condoms, and partner's vasectomy
 are NOT acceptable methods of contraception.

 -  Women who have been postmenopausal for at least 1 year or have had a
 hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation at least 6
 months prior to signing the informed consent form.

 -  Subjects with a competent mental condition to provide written informed consent before
 entering the study.

 Exclusion Criteria:

 -  Any other formal indication for the use of a thienopyridine.

 -  Subjects with a history of refractory ventricular arrhythmias.

 -  Subjects with a history of an implantable defibrillator device.

 -  Subjects with a history or evidence of congestive heart failure (New York Heart
 Association [NYHA] Class III or above) within 6 months prior to screening.

 -  Subjects with significant hypertension (systolic blood pressure >180 mmHg or diastolic
 blood pressure >110 mmHg) at either the time of screening or baseline assessment.

 -  Bleeding Risk Exclusion Criteria:

 -  Any known contraindication to treatment with an anticoagulant or antiplatelet
 agent

 -  Prior history or clinical suspicion of cerebral vascular malformations,
 intracranial tumor, transient ischemic attack (TIA), or stroke, or recent history
 (within 3 months) of head trauma

 -  Prior history or presence of significant bleeding disorders (eg, hematemesis,
 melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intraocular
 bleeding)

 -  History (within the last 5 years) or presence of gastric ulcers. Previous history
 of duodenal ulcer is acceptable but must have been successfully surgically or
 medically treated with no further evidence of disease in the past 6 months (from
 screening).

 -  Prior history of abnormal bleeding tendency (ie, prolonged bleeding on dental
 extraction, tonsillectomy, or previous surgical procedure)

 -  Known prior history of thrombocytopenia (platelet count < 100,000/mm³) or
 thrombocytosis (platelet count > 500,000/mm³) or recent history (within six
 months) of hemoglobin < 10 mg/dL

 -  Clinically significant out of range values for prothrombin time, activated
 partial thromboplastin time (aPTT), platelet count, or hemoglobin at screening,
 in the investigator's opinion

 -  History of major surgery, severe trauma, fracture, or organ biopsy within 3
 months prior to enrollment

 -  Prior/Concomitant Therapy Exclusion Criteria:

 -  Subjects taking prasugrel, clopidogrel, ticlopidine, cilostazol, dipyridamole,
 warfarin, heparin, direct thrombin inhibitors, or glycoprotein IIB/IIIa
 inhibitors =10 days prior to screening or during study participation

 -  The use (or planned use) of fibrinolytic agents within 30 days before screening
 or during study participation

 -  Subjects receiving treatment with nonsteroidal anti-inflammatory drugs (NSAIDs)
 or cyclooxygenase-2 (COX-2) inhibitors exceeding 3 doses per week

 -  Subjects receiving proton pump inhibitors (PPIs), eg, (lansoprazole,
 esomeprazole, omeprazole, pantoprazole, or rabeprazole) =10 days prior to
 screening or during study participation

 -  General Exclusion Criteria:

 -  Investigator site personnel directly affiliated with the study or immediate
 family of investigator site personnel directly affiliated with the study.
 Immediate family is defined as a spouse, parent, child, or sibling, whether
 biological or legally adopted

 -  Daiichi Sankyo or Eli Lilly employees

 -  Currently enrolled in, or discontinued within the last 30 days prior to baseline
 from, a clinical study involving an off-label use of an investigational drug or
 device, or concurrently enrolled in a non-observational clinical study or any
 other type of medical research judged not to be scientifically or medically
 compatible with this study

 -  Have previously completed or withdrawn from this study

 -  Women who are known to be pregnant and/or who receive a positive serum pregnancy
 test result, who have given birth within the past 90 days, and/or who are
 breastfeeding

 -  Results of clinical laboratory tests at the time of screening that are judged to
 be clinically significant for the subject, as determined by the investigator

 -  Known allergies or intolerance to aspirin and/or thienopyridines (prasugrel,
 clopidogrel, or ticlopidine)

 -  Evidence of significant active neuropsychiatric disease, alcohol abuse or drug
 abuse, in the investigator's opinion

 -  Evidence of active hepatic disease, or any of the following; positive human
 immunodeficiency virus (HIV) antibodies, positive hepatitis C antibody, positive
 hepatitis B surface antigen; serum alanine transaminase (ALT), aspartate
 transaminase (AST), or gamma-glutamyltransferase (GGT) >/= 3 times the upper
 limit of normal (ULN) laboratory reference range; or bilirubin >/= 2 times the
 ULN of laboratory reference range at screening

 -  Subjects who are unreliable and unwilling to make themselves available for the
 duration of the study and who will not abide by the research unit policy and
 procedure and study restrictions

 -  Subjects who have had an angiogram </= 7 days before randomization