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

NCT00684203 | Completed Phase 2 Results DMC

• 1 other identifier: P04772
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Atherosclerosis; Myocardial Ischemia; Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

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

  Up to Day 60

Secondary Outcomes (15)

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

  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

  Up to Day 60

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

  Baseline, Day 30, Day 60, Day 74, Day 90, Day 121

• Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels Among Participants Who Underwent PCI By Study Visit

  Baseline, Day 30, Day 60

• Mean CD40 Ligand Levels Among Participants Who Underwent PCI

  Baseline, Day 30, Day 60

Study Arms (5)

Vorapaxar 20 mg/1 mg

EXPERIMENTAL

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

Drug: Vorapaxar; Drug: Aspirin; Drug: Clopidogrel

Vorapaxar 20 mg/2.5 mg

EXPERIMENTAL

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

Drug: Vorapaxar; Drug: Aspirin; Drug: Clopidogrel

Vorapaxar 40 mg/1 mg

EXPERIMENTAL

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

Drug: Vorapaxar; Drug: Aspirin; Drug: Clopidogrel

Vorapaxar 40 mg/2.5 mg

EXPERIMENTAL

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

Drug: Vorapaxar; Drug: Aspirin; Drug: Clopidogrel

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Aspirin; Drug: Clopidogrel

Interventions

Vorapaxar 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

Vorapaxar 20 mg/1 mg; Vorapaxar 20 mg/2.5 mg; Vorapaxar 40 mg/1 mg; Vorapaxar 40 mg/2.5 mg

Placebo DRUG

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

Placebo

Aspirin DRUG

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

Also known as: ASA, acetylsalicylic acid

Placebo; Vorapaxar 20 mg/1 mg; Vorapaxar 20 mg/2.5 mg; Vorapaxar 40 mg/1 mg; Vorapaxar 40 mg/2.5 mg

Clopidogrel DRUG

100 mg two or three times daily for 60 days.

Placebo; Vorapaxar 20 mg/1 mg; Vorapaxar 20 mg/2.5 mg; Vorapaxar 40 mg/1 mg; Vorapaxar 40 mg/2.5 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 20124733 RESULT

MeSH Terms

Conditions

Atherosclerosis; Myocardial Ischemia; Myocardial Infarction

Interventions

vorapaxar; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2008
• First Posted: May 26, 2008
• Study Start: December 1, 2006
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: May 5, 2017
• Results First Posted: August 15, 2014

Record last verified: 2017-03