The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease

Subjects will be stratified according to smoking status prior to being randomized to 1 of the
2 treatment sequences: prasugrel 10 mg daily for 10 days followed by clopidogrel 75 mg daily
for 10 days or clopidogrel 75 mg daily for 10 days followed by prasugrel 10 mg daily for 10
days. There will be a 14-day Washout Period between Active Treatment Period 1 (when subjects
receive the first drug of the sequence) and the second Active Treatment Period 2 (Period 3)
(when subjects receive the second drug of the sequence). All subjects will remain on the same
dose of aspirin from baseline throughout the study.

Inclusion Criteria:

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

- Weight > or = 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 CAD, defined as any of the following:

- Chronic stable angina;

- Documented prior ACS event > or = 30 days before screening and not currently
prescribed or currently on thienopyridine therapy;

- Previous coronary revascularization including percutaneous transluminal coronary
angioplasty, stent, or coronary artery bypass graft;

- Coronary Artery Disease (> or = 40% obstruction) in at least one coronary vessel
after angiography;

- Documented history of positive stress test; or

- High coronary artery calcium score (> or = 90th percentile for age and gender)
determined by cardiac computed tomography scan;

- Current smokers who smoke > or = ½ pack per day of cigarettes with a NicAlert™ level
of 6;

- Non-smokers with a NicAlert level of 0, 1, or 2;

- Female subjects who meet one of the following:

- Women of childbearing potential with a negative serum pregnancy test at
screening, who are not breastfeeding, 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 intrauterine device, diaphragm plus
spermicide, or female condom plus spermicide. Abstinence, partner's use of
condoms, partner's vasectomy, and hormonal contraceptives 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 (ICF); and

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

Exclusion Criteria:

- Subjects who received a bare metal stent and/or a drug-eluting stent within the last
12 months;

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

- 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 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, 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 or presence of thrombocytopenia (platelet count <100,000/mm3)
or thrombocytosis (platelet count >500,000/mm3) or recent history (within 6
months) of hemoglobin <10 mg/dL;

- International normalized ratio (INR) >1.5 or activated partial thromboplastin
time (aPTT) > upper limit of normal (ULN) of laboratory reference range at
screening;

- 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 GPIIb/IIIa inhibitors < or = 10
days prior to randomization or during study participation;

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

- Subjects receiving treatment with nonsteroidal anti-inflammatory drugs or
cyclooxygenase-2 inhibitors exceeding 3 doses per week;

- Subjects taking proton pump inhibitors (eg, lansoprazole, esomeprazole,
omeprazole, pantoprazole, or rabeprazole) < or = 10 days prior to randomization
or during study participation;

- Use or planned use of any herbal supplements < or = 10 days prior to
randomization or during study participation;

- Use or planned use of the following strong inhibitors of various CYP pathways <
or =10 days prior to randomization or during study participation: ciprofloxacin,
cimetidine, fluvoxamine, estradiol, ethinylestradiol, fluconazole, amiodarone,
indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, erythromycin,
telithromycin, itraconazole, ketoconazole, fluconazole, nefazodone, or
grapefruit-containing products;

- Use or planned use of the following strong inducers of various CYP pathways < or
= 10 days prior to randomization or during study participation: rifampin,
barbiturates, carbamazepine, dexamethasone, or St. John's Wort;

- Female subjects taking hormonal contraception or hormonal replacement therapy
during study participation;

- General exclusion criteria:

- Investigative site personnel directly affiliated with the study or immediate
family of investigative 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 from, any clinical
study involving an investigational drug or device;

- 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, and/or 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 antibodies; positive hepatitis C antibody; positive
hepatitis B surface antigen; serum alanine transaminase, aspartate transaminase,
or gamma-glutamyltransferase > or = 3 × ULN of laboratory reference range; or
bilirubin > or = 2 × ULN of laboratory reference range at screening;

- Subjects who are 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.