- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00684203
Trial to Assess the Safety and Effects of Vorapaxar in Japanese Subjects With Acute Coronary Syndrome (P04772; MK-5348-016)
March 31, 2017 updated by: Merck Sharp & Dohme LLC
Phase II Study of SCH 530348 in Subjects With Acute Coronary Syndrome
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.
Study Overview
Status
Completed
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
120
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Vorapaxar 20 mg/1 mg
Vorapaxar 20 mg loading dose + daily 1 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
|
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
Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.
Other Names:
100 mg two or three times daily for 60 days.
|
Experimental: Vorapaxar 20 mg/2.5 mg
Vorapaxar 20 mg loading dose + daily 2.5 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
|
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
Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.
Other Names:
100 mg two or three times daily for 60 days.
|
Experimental: Vorapaxar 40 mg/1 mg
Vorapaxar 40 mg loading dose + daily 1 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
|
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
Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.
Other Names:
100 mg two or three times daily for 60 days.
|
Experimental: Vorapaxar 40 mg/2.5 mg
Vorapaxar 40 mg loading dose + daily 2.5 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
|
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
Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.
Other Names:
100 mg two or three times daily for 60 days.
|
Placebo Comparator: Placebo
Placebo loading dose + daily placebo maintenance dose + standard of care (Aspirin + Ticlopidine)
|
Loading dose of 75-325 mg on Day 1, then 75-100 mg once daily for 60 days.
Other Names:
100 mg two or three times daily for 60 days.
Oral tablets; matching placebo for SCH 530348 loading and maintenance doses for 59 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing Adverse Events (AEs) Who Underwent Percutaneous Coronary Interventions (PCI)
Time Frame: Up to Day 60
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing Non-Major Adverse Cardiac Events (MACE) Who Underwent PCI
Time Frame: Up to Day 121
|
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.
|
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
Time Frame: Up to Day 60
|
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.
|
Up to Day 60
|
Number of Participants Who Underwent PCI With Inhibition of Platelet Aggregation By Study Visit
Time Frame: Baseline, Day 30, Day 60, Day 74, Day 90, Day 121
|
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.
|
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
Time Frame: Baseline, Day 30, Day 60
|
Participant blood samples were collected at Baseline and on Days 30 and 60 to evaluate the median level of hs-CRP.
hs-CRP is a protein marker in the blood associated with inflammation with higher values indicating a greater degree of inflammation.
Analysis of data was by maintenance dose group.
|
Baseline, Day 30, Day 60
|
Mean CD40 Ligand Levels Among Participants Who Underwent PCI
Time Frame: Baseline, Day 30, Day 60
|
Participant blood samples were collected at Baseline and Days 30 and 60 to evaluate the mean level of CD40 ligand present.
CD40 ligand is a protein primarily found on activated T-cells, with higher levels indicating better immunological health.
Analysis of data was by maintenance dose group.
|
Baseline, Day 30, Day 60
|
Mean Membrane-Bound P-Selectin Levels Among Participants Who Underwent PCI
Time Frame: Baseline, Day 30, Day 60
|
Participant blood samples were collected at Baseline and Days 30 and 60 to evaluate the mean level of membrane-bound P-selectin.
Membrane-bound P-selectin was measured using flow cytometry and a monoclonal antibody to P-selectin.
Intensity levels are reported in arbitrary units 0 (dark) to 1023 (bright).
Higher values correspond to greater membrane-bound P-Selectin levels.
Analysis of data was by maintenance dose group.
|
Baseline, Day 30, Day 60
|
Number of Participants Who Underwent PCI With Clinically Important Bleeding Events During Treatment and After Hospital Discharge
Time Frame: Up to Day 121
|
Clinically important bleeding events were defined as intracranial hemorrhage, bleeding requiring hospitalization, or TIMI major bleeding.
Analysis of data was by loading/maintenance dose group.
|
Up to Day 121
|
Number of Participants With Major, Minor, and Non-TIMI Bleeding Events Among Participants Who Did Not Undergo PCI
Time Frame: Up to Day 60
|
Major TIMI bleeding was defined as any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo 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 loading dose group.
|
Up to Day 60
|
Number of Participants Experiencing Non-MACE AEs Among Participants Who Did Not Undergo PCI
Time Frame: Up to Day 121
|
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 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 dose group.
|
Up to Day 121
|
Number of Participants Who Did Not Undergo PCI But Had Coronary Artery Bypass Graft (CABG) Who Experienced Bleeding Events
Time Frame: Up to 10 Hours Post-CABG
|
Bleeding events were evaluated up to 10 hours post-CABG among participants who did not undergo PCI.
|
Up to 10 Hours Post-CABG
|
Number of Participants Who Did Not Undergo PCI But Had Bleeding Events That Required Transfusion
Time Frame: Up to Day 60
|
Bleeding events were evaluated among participants that did not undergo PCI to determine the number of participants that required blood transfusion.
Analysis of data was by loading dose group.
|
Up to Day 60
|
Number of Participants Who Did Not Undergo PCI But Had Bleeding Events That Required Subsequent Hospitalization
Time Frame: Up to Day 30
|
Bleeding events were evaluated among participants that did not undergo PCI to determine the number of participants who required a subsequent hospitalization.
Analysis of data was by loading dose group.
|
Up to Day 30
|
Median Hs-CRP Levels Among Participants Who Did Not Undergo PCI
Time Frame: Baseline Up To Day 60
|
Participant blood samples were collected at baseline and at the time of hospital discharge to determine the median serum level of hs-CRP.
Analysis of data was by loading dose group.
|
Baseline Up To Day 60
|
Mean CD40 Ligand Levels Among Participants Who Did Not Undergo PCI
Time Frame: Baseline Up To Day 60
|
Participant blood samples were collected at baseline and at the time of hospital discharge to determine the mean serum level of CD40 ligand.
Analysis of data was by loading dose group.
|
Baseline Up To Day 60
|
Number of Participants Who Did Not Undergo PCI That Had Clinically Important Bleeding Events
Time Frame: Baseline Up To Day 60
|
Clinically important bleeding events were defined as intracranial hemorrhage, bleeding requiring blood transfusion, bleeding requiring hospitalization, and TIMI major bleeding.
Analysis of data was by loading dose group.
|
Baseline Up To Day 60
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2006
Primary Completion (Actual)
October 1, 2007
Study Completion (Actual)
October 1, 2007
Study Registration Dates
First Submitted
May 22, 2008
First Submitted That Met QC Criteria
May 22, 2008
First Posted (Estimate)
May 26, 2008
Study Record Updates
Last Update Posted (Actual)
May 5, 2017
Last Update Submitted That Met QC Criteria
March 31, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Necrosis
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Myocardial Infarction
- Infarction
- Myocardial Ischemia
- Ischemia
- Atherosclerosis
- Acute Coronary Syndrome
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Purinergic P2Y Receptor Antagonists
- Purinergic P2 Receptor Antagonists
- Purinergic Antagonists
- Purinergic Agents
- Aspirin
- Clopidogrel
- Vorapaxar
Other Study ID Numbers
- P04772
Plan for Individual participant data (IPD)
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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