Trial to Assess the Safety of Vorapaxar in Japanese Subjects With Cerebral Infarction (P05005; MK-5348-017)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Cerebral Infarction

Treatments: Drug: Vorapaxar 1 mg; Drug: Aspirin 75-150 mg; Drug: Placebo; Drug: Vorapaxar 2.5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00684515

P05005

Details and patient eligibility

About

The study is designed to assess safety of Vorapaxar when added to standard of care (aspirin) in Japanese subjects with cerebral infarction. The study will assess incidence and tolerability of bleeding, major adverse cardiac events, all adverse events, and effect on expression of markers of inflammation.

Enrollment: 90 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men and women at least 18 years old with last cerebral infarction (excluding cardiogenic cerebral embolism) having occurred from 14 days to less than 1 year after onset (at the time of obtaining consent), with stable nervous system for more than 24 hours and known course of disease.
• Participants confirmed to have cerebral infarction lesion by brain computerized tomography (CT) or magnetic resonance imaging (MRI).
• Both of in-participant and out-participant
• Willing to give appropriate informed consent and complete all study-related procedures and able to adhere to dosing and visit schedules.
• Women of child-bearing potential (all postmenopausal women who are <1 year 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 study drug, and for 60 days after completion or discontinuation of the medication.

Exclusion criteria

• Pregnancy and nursing patients (premenopausal women should have a negative pregnancy test result confirmed before enrollment)
• Participant with any serious complication or any condition that the investigator feels that would cause a significant hazard to the participant if the study drug is administered.
• Known hypersensitivity to any component of the study drug.
• Participation in a study or use of an investigational study drug within 30 days before obtaining consent.
• Member of the staff personnel directly involved with this study
• Family member of the study staff.
• History of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before obtaining consent.
• History of cerebral hemorrhage.
• Severe hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg).
• Major surgery within 2 weeks before obtaining consent.
• Known platelet count <100,000/mm^3
• Participants confirmed to have cerebral bleeding or any causes of cerebral bleeding by brain CT or MRI.
• Participants with transient ischemic attack (TIA), progressive stroke or cardiogenic cerebral embolism.
• 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 system or hepatic disease, or aspartate aminotransferase (GOT) or alanine aminotransferate (GPT) activity more than two times greater than the upper limit of the laboratory normal range.
• Participants with contraindictation to aspirin.
• Scheduled to have PCI (peripheral coronary intervention), peripheral interventional event, carotid endarterectomy, intra- and extra- cranial bypass surgery and intravascular surgery (angioplasty) during the study period.
• Combination therapy with unfractionated heparin, tissue plasminogen activator, urokinase, warfarin, factor Xa inhibitor, direct thrombin inhibitor or antiplatelet agents other than aspirin after obtaining consent, or scheduled to have the above combination therapy.
• Any serious impairment which would make detection of new ischemic events difficult (eg, bedridden participants, participants with total nursing care, dementia participants, etc.) or consciousness disturbance which may cause aspiration of the study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 3 patient groups, including a placebo group

Vorapaxar 2.5 mg + Aspirin

Experimental group

Description:

Vorapaxar oral tablets; once daily for 60 days + Aspirin.

Treatment:

Drug: Aspirin 75-150 mg

Drug: Vorapaxar 2.5 mg

Vorapaxar 1 mg + Aspirin

Experimental group

Description:

Vorapaxar oral tablets; once daily for 60 days + Aspirin.

Treatment:

Drug: Vorapaxar 1 mg

Drug: Aspirin 75-150 mg

Placebo + Aspirin

Placebo Comparator group

Description:

Placebo oral tablets; once daily for 60 days + Aspirin

Treatment:

Drug: Aspirin 75-150 mg

Drug: Placebo