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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Myocardial Ischemia; Myocardial Infarction; Atherosclerosis

Treatments: Drug: Vorapaxar; Drug: Placebo; Drug: Clopidogrel; Drug: Aspirin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00684203

P04772

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 5 patient groups, including a placebo group

Vorapaxar 20 mg/1 mg

Experimental group

Description:

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

Treatment:

Drug: Vorapaxar

Drug: Aspirin

Drug: Clopidogrel

Vorapaxar 20 mg/2.5 mg

Experimental group

Description:

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

Treatment:

Drug: Vorapaxar

Drug: Aspirin

Drug: Clopidogrel

Vorapaxar 40 mg/1 mg

Experimental group

Description:

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

Treatment:

Drug: Vorapaxar

Drug: Aspirin

Drug: Clopidogrel

Vorapaxar 40 mg/2.5 mg

Experimental group

Description:

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

Treatment:

Drug: Vorapaxar

Drug: Aspirin

Drug: Clopidogrel

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Aspirin

Drug: Placebo

Drug: Clopidogrel