Prasugrel/Clopidogrel Maintenance Dose Washout Study
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Intervention: Prasugrel; Clopidogrel
Intervention description: Prasugrel 10mg tablet administered once daily for 7 days.
After a 1-day to 14-day screening period, participants will receive active treatment with either prasugrel or clopidogrel for 7 days. If a participant has not missed more than 1 dose of study medication and is unable to attend Visit 3 (Washout Day 1) the day after the 7th day of study medication, the participant may take up to an additional 3 days of study medication and proceed to Visit 3 the day after the last dose. Active treatment will be followed by a 1-day to 12-day Washout Period depending on the time to reach both of the exit criteria.; Clopidogrel 75 mg tablet administered once daily for 7 days.
After a 1-day to 14-day screening period, participants will receive active treatment with either prasugrel or clopidogrel for 7 days. If a participant has not missed more than 1 dose of study medication and is unable to attend Visit 3 (Washout Day 1) the day after the 7th day of study medication, the participant may take up to an additional 3 days of study medication and proceed to Visit 3 the day after the last dose. Active treatment will be followed by a 1-day to 12-day Washout Period depending on the time to reach both of the exit criteria.
Intervention MeSH terms: Clopidogrel; Prasugrel Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: thienopyridine; pharmacologic action; prasugrel; clopidogrel

Summary:

      The primary objective of the study is to describe the cumulative proportion of participants
      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.
    

Eligibility criteria:

        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 Myocardial
                  Infarction [STEMI] or non-ST elevation Myocardial Infarction [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