Prasugrel/Clopidogrel Maintenance Dose Washout Study

NCT01014624 | Completed Phase 4 Results

• 1 other identifier: CS747S-B-U4001
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 4

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

Keywords

thienopyridine; pharmacologic action; prasugrel; clopidogrel

Outcome Measures

Primary Outcomes (2)

• The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Primary Definition of Return to Baseline

  On the first day of the Washout Period (Visit 3), the blood draw for platelet function testing was obtained 24 hours (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%. The results are expressed as cumulative percentage of participants.

  up to 12 days after last dose

• The Time to Return to Baseline Platelet Function as Assessed by P2Y12 Reaction Units (PRU) Using the Accumetrics VerifyNOW P2Y12 Device Based on the Secondary Definition of Return to Baseline

  On the first day of the Washout Period (visit 3), the blood draw for platelet function testing was obtained 24 hours (+/- 6 hours) after the last dose of study medication. Following Visit 3, platelet function testing was performed during each visit of the Washout Period until the participant met the following exit criteria: (Baseline PRU-PRU) less than or equal to 60 units and (Baseline PRU-PRU)/(Baseline PRU) less than or equal to 20%.

  up to 12 days after last dose

Secondary Outcomes (6)

• Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Primary Definition of Return to Baseline Using the Primary Population

  up to 12 days after last dose

• Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on Secondary Definition of Return to Baseline Using the Primary Population

  up to 12 days after last dose

• Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Primary Definition of Return to Baseline Using the Responder Population

  up to 12 days after last dose

• Day at Which 50%, 75%, and 90% of Participants Returned to Baseline Platelet Function Based on the Secondary Definition of Return to Baseline Using the Responder Population

  up to 12 days after the last dose

• Percentage of Inhibition of Platelet Aggregation on Washout Day 1

  Washout Day 1

Study Arms (2)

Prasugrel

EXPERIMENTAL

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

Drug: Prasugrel

Clopidogrel

ACTIVE COMPARATOR

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

Drug: Clopidogrel

Interventions

Prasugrel 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.

Also known as: Effient

Prasugrel

Clopidogrel 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.

Also known as: Plavix

Clopidogrel

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (4)

Scripps Clinic

La Jolla, California, 92037, United States

Location

University of Florida Health Science Center Shands Jacksonville

Jacksonville, Florida, 32209, United States

Location

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45212, United States

Location

Black Hills Clinical Research Center

Rapid City, South Dakota, 57701, United States

Location

Related Publications (1)

• 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.

  PMID: 22698488 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Brian Baker
• Organization: Daiichi Sankyo, Inc.

bbaker@dsi.com

973-944-2712

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: November 17, 2009
• Study Start: February 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: June 1, 2010
• Last Updated: June 28, 2021
• Results First Posted: September 9, 2011

Record last verified: 2021-06

Locations

US (4)