Prasugrel/Clopidogrel Maintenance Dose Washout Study

NCT ID: NCT01014624

Last Updated: 2021-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2010-06-30

Brief 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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Prasugrel

Prasugrel 10mg administered for 7 days followed by a Washout Period up to 12 days.

Group Type: EXPERIMENTAL

Prasugrel

Intervention Type: DRUG

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

Clopidogrel 75mg administered for 7 days followed by a 12 day Washout Period up to 12 days.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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.

Interventions

Prasugrel

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.

Intervention Type: DRUG

Clopidogrel

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 Type: DRUG

Other Intervention Names

Effient; Plavix

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.

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Scripps Clinic

La Jolla, California, United States

University of Florida Health Science Center Shands Jacksonville

Jacksonville, Florida, United States

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, United States

Black Hills Clinical Research Center

Rapid City, South Dakota, United States

Countries

United States

References

Price MJ, Walder JS, Baker BA, Heiselman DE, Jakubowski JA, Logan DK, Winters KJ, Li W, Angiolillo DJ. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. J Am Coll Cardiol. 2012 Jun 19;59(25):2338-43. doi: 10.1016/j.jacc.2012.02.042.

Reference Type: DERIVED

PMID: 22698488 (View on PubMed)

Other Identifiers

CS747S-B-U4001

Identifier Type: -

Identifier Source: org_study_id