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

Merck Sharp & Dohme LLC120 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

120

Conditions

Atherosclerosis Myocardial Ischemia Myocardial Infarction

Interventions

VorapaxarDRUG

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

PlaceboDRUG

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

AspirinDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Participants Experiencing Adverse Events (AEs) Who Underwent Percutaneous Coronary Interventions (PCI)

Time frame: Up to Day 60

Secondary Outcomes

Number of Participants Experiencing Non-Major Adverse Cardiac Events (MACE) Who Underwent PCI

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. MACE events were defined as nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization due to recurrent ischemia, or urgent coronary revascularization performed ≥ 30 days after administration of the loading dose (Day 1). All MACE events were excluded from this analysis. Analysis of data was by loading/maintenance dose group.

Time frame: Up to Day 121

Number of Participants With Major, Minor, and Non-Thrombolysis in Myocardial Infarction Cooperative Group (TIMI) Bleeding Events Among Participants Who Underwent PCI

Major TIMI bleeding was defined as any intracranial bleeding (excluding microhemorrhages \<10 mm evident only on gradient-echo magnetic resonance imaging \[MRI\]), clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL, or fatal bleeding (bleeding that directly results in death within 7 days). Minor TIMI bleeding was defined as any clinically overt bleeding resulting in hemoglobin drop of 3 to \<5 g/dL. Non-TIMI bleeding included all bleeding events not covered under Major TIMI bleeding or Minor TIMI bleeding. Analysis of data was by maintenance dose group.

Time frame: Up to Day 60

Number of Participants Who Underwent PCI With Inhibition of Platelet Aggregation By Study Visit

Blood samples were collected from participants at Baseline and Days 30, 60, 74, 90, and 121 to determine the extent of inhibition of platelet aggregation induced by thrombin-receptor agonist peptide (TRAP). Analysis of data was by maintenance dose group.

Data from ClinicalTrials.gov

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