Trial to Assess the Safety and Effects of Vorapaxar in Japanese Subjects With Acute Coronary Syndrome (P04772; MK-5348-016)

NCT ID: NCT00684203

Last Updated: 2017-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-01
• Study Completion Date: 2007-10-01

Brief Summary

The study is designed to assess safety and effects of vorapaxar, when added to standard of care (aspirin and clopidigrel), in Japanese subjects with acute coronary syndrome. The study may also provide information about the effect of vorapaxar on preventing heart attack and stroke in this subject population.

Detailed Description

The study drug (loading dose) is administered at least 1 hour before catheterization for diagnostic imaging or percutaneous coronary interventions (PCI). The incidence of bleeding is thought to be an important index to assess the safety of this drug, therefore thrombolysis in myocardial infarction (TIMI) is evaluated.

Conditions

Atherosclerosis; Myocardial Ischemia; Myocardial Infarction

Study Design

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

Study Groups

Vorapaxar 20 mg/1 mg

Vorapaxar 20 mg loading dose + daily 1 mg maintenance dose + standard of care (Aspirin + Ticlopidine)

Group Type: EXPERIMENTAL

Vorapaxar

Intervention Type: DRUG

Oral tablets; single 20-mg or 40-mg loading dose on first day followed by daily 1-mg or 2.5-mg maintenance dose for 59 days

Aspirin

Intervention Type: DRUG

Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.

Clopidogrel

Intervention Type: DRUG

100 mg two or three times daily for 60 days.

Vorapaxar 20 mg/2.5 mg

Vorapaxar 20 mg loading dose + daily 2.5 mg maintenance dose + standard of care (Aspirin + Ticlopidine)

Group Type: EXPERIMENTAL

Vorapaxar

Intervention Type: DRUG

Oral tablets; single 20-mg or 40-mg loading dose on first day followed by daily 1-mg or 2.5-mg maintenance dose for 59 days

Aspirin

Intervention Type: DRUG

Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.

Clopidogrel

Intervention Type: DRUG

100 mg two or three times daily for 60 days.

Vorapaxar 40 mg/1 mg

Vorapaxar 40 mg loading dose + daily 1 mg maintenance dose + standard of care (Aspirin + Ticlopidine)

Group Type: EXPERIMENTAL

Vorapaxar

Intervention Type: DRUG

Oral tablets; single 20-mg or 40-mg loading dose on first day followed by daily 1-mg or 2.5-mg maintenance dose for 59 days

Aspirin

Intervention Type: DRUG

Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.

Clopidogrel

Intervention Type: DRUG

100 mg two or three times daily for 60 days.

Vorapaxar 40 mg/2.5 mg

Vorapaxar 40 mg loading dose + daily 2.5 mg maintenance dose + standard of care (Aspirin + Ticlopidine)

Group Type: EXPERIMENTAL

Vorapaxar

Intervention Type: DRUG

Oral tablets; single 20-mg or 40-mg loading dose on first day followed by daily 1-mg or 2.5-mg maintenance dose for 59 days

Aspirin

Intervention Type: DRUG

Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.

Clopidogrel

Intervention Type: DRUG

100 mg two or three times daily for 60 days.

Placebo

Placebo loading dose + daily placebo maintenance dose + standard of care (Aspirin + Ticlopidine)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral tablets; matching placebo for SCH 530348 loading and maintenance doses for 59 days

Aspirin

Intervention Type: DRUG

Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.

Clopidogrel

Intervention Type: DRUG

100 mg two or three times daily for 60 days.

Interventions

Vorapaxar

Oral tablets; single 20-mg or 40-mg loading dose on first day followed by daily 1-mg or 2.5-mg maintenance dose for 59 days

Intervention Type: DRUG

Placebo

Oral tablets; matching placebo for SCH 530348 loading and maintenance doses for 59 days

Intervention Type: DRUG

Aspirin

Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.

Intervention Type: DRUG

Clopidogrel

100 mg two or three times daily for 60 days.

Intervention Type: DRUG

Other Intervention Names

ASA, acetylsalicylic acid

Eligibility Criteria

Inclusion Criteria

• Men and women aged 18 years or more with history of cardiac ischemia related chest discomfort of > 10 minutes duration < 24 hours prior to randomization, and having at least 1 of the following A or B. Participants who are planned to undergo PCI will be the target participants.

• A: Positive biomarkers [Elevated troponin I or creatinine kinase MB isozyme greater than the site's upper limit of normal (ULN)] at or before registration
• B: Electrocardiogram (ECG) changes: ST segment depression >= 0.1 mV (>=1 mm), or transient (<30 minutes) ST segment elevation >= 0.1 mV (>=1 mm) in at least 2 contiguous leads
• Willing to give appropriate informed consent and complete all study-related procedures, and able to adhere to dosing and all visit schedules.
• Women of child-bearing potential (all postmenarchal women who are <1 years menopausal or who have not had surgical sterilization or a hysterectomy are considered to be women of child-bearing potential) must agree to use a medically accepted method of contraception while receiving protocol-specified medication, and for 60 days after stopping the medication.

Exclusion Criteria

• Pregnant and nursing mothers (premenopausal women should have a negative pregnancy test result confirmed before enrollment)
• Any serious illness or any condition that the investigator feels would pose a significant hazard to the participant if investigational therapy were initiated
• known hypersensitivity to any component of the current investigational product;
• Participation in a study of experimental therapy or use of any investigational drug within 30 days before enrollment
• Member of the staff personnel directly involved with this study;
• Family member of the investigational study staff;
• History of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before enrollment
• History of a hemorrhagic stroke at any time
• Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) while receiving therapy;
• Major surgery within 2 weeks prior to enrollment
• Known platelet count <100,000/mm^3
• Uncontrolled cardiac arrhythmia;
• Known impairment of renal function (serum creatinine >2.0 mg/dL [>176.8 umol/L]), dysproteinemia, nephrotic syndrome, or other renal disease;
• Active or chronic hepatobiliary or hepatic disease, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activity more than two times greater than the upper limit of the laboratory reference range
• Anticipated staged PCI
• Concurrent or anticipated treatment with warfarin, factor Xa inhibitor, direct thrombin inhibitor, or antiplatelet agents except aspirin and ticlopidine after enrollment
• Anticipated intracoronary brachytherapy

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

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Goto S, Yamaguchi T, Ikeda Y, Kato K, Yamaguchi H, Jensen P. Safety and exploratory efficacy of the novel thrombin receptor (PAR-1) antagonist SCH530348 for non-ST-segment elevation acute coronary syndrome. J Atheroscler Thromb. 2010 Feb 26;17(2):156-64. doi: 10.5551/jat.3038. Epub 2010 Feb 3.

Reference Type: RESULT

PMID: 20124733 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

P04772

Identifier Type: -

Identifier Source: org_study_id