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

NCT00684515 | Completed Phase 2 Results DMC

• 1 other identifier: P05005
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cerebral Infarction

Outcome Measures

Primary Outcomes (1)

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

  An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporarily associated with study drug administration, whether or not considered related to study drug. MACE events were defined as nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization due to recurrent ischemia, or urgent coronary revascularization. All MACE events were excluded from this analysis.

  Up to Day 121

Secondary Outcomes (5)

• Number of Paticipants Experiencing Thrombolysis in Myocardial Infarction (TIMI) Major, Minor, and Non-TIMI Bleeding Events

  Up to Day 60

• Number of Participants With MACE or Death

  Up to Day 121

• Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit

  Up to Day 60

• Mean CD40 Ligand Levels By Study Visit

  Up to Day 60

• Mean Membrane-Bound P-Selectin Levels By Study Visit

  Up to Day 60

Study Arms (3)

Vorapaxar 2.5 mg + Aspirin

EXPERIMENTAL

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

Drug: Vorapaxar 2.5 mg; Drug: Aspirin 75-150 mg

Vorapaxar 1 mg + Aspirin

EXPERIMENTAL

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

Drug: Vorapaxar 1 mg; Drug: Aspirin 75-150 mg

Placebo + Aspirin

PLACEBO COMPARATOR

Placebo oral tablets; once daily for 60 days + Aspirin

Drug: Placebo; Drug: Aspirin 75-150 mg

Interventions

Vorapaxar 2.5 mg DRUG

Oral tablets; once daily for 60 days.

Vorapaxar 2.5 mg + Aspirin

Vorapaxar 1 mg DRUG

Oral tablets; once daily for 60 days

Vorapaxar 1 mg + Aspirin

Placebo DRUG

oral tablets; once daily for 60 days

Placebo + Aspirin

Aspirin 75-150 mg DRUG

oral tablets; once daily for 60 days

Placebo + Aspirin; Vorapaxar 1 mg + Aspirin; Vorapaxar 2.5 mg + Aspirin

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Shinohara Y, Goto S, Doi M, Jensen P. Safety of the novel protease-activated receptor-1 antagonist vorapaxar in Japanese patients with a history of ischemic stroke. J Stroke Cerebrovasc Dis. 2012 May;21(4):318-24. doi: 10.1016/j.jstrokecerebrovasdis.2010.09.005. Epub 2010 Oct 14.

  PMID: 20947374 RESULT

MeSH Terms

Conditions

Cerebral Infarction

Interventions

vorapaxar; Aspirin

Condition Hierarchy (Ancestors)

Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular 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

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: September 21, 2006
• Primary Completion: November 8, 2007
• Study Completion: November 8, 2007
• Last Updated: September 21, 2018
• Results First Posted: July 29, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share