Trial to Assess the Safety and Effects of SCH 530348 in Japanese Subjects With Acute Coronary Syndrome (P04772/MK-5348-016)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00684203
First received: May 22, 2008
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

The study is designed to assess safety and effects of SCH 530348, 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 SCH 530348 on preventing heart attack and stroke in this subject population.


Condition Intervention Phase
Atherosclerosis
Myocardial Ischemia
Myocardial Infarction
Drug: SCH 530348
Drug: Placebo
Drug: Aspirin
Drug: Ticlopidine hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Study of SCH 530348 in Subjects With Acute Coronary Syndrome

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • The primary endpoint is the incidence of adverse events. [ Time Frame: During treatment with study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary endpoints for subjects who underwent PCI included the incidence of adverse events. [ Time Frame: To the end of the post treatment observation period (Day 121) ] [ Designated as safety issue: Yes ]
  • For subjects who underwent PCI included TIMI major/minor and non TIMI bleeding, 1st occurrence or certain combo of major adverse cardiac events and death, inhibition of platelet aggregation, and change in hs-CRP, CD40 ligand, & membrane-bound P-selectin. [ Time Frame: During treatment with study drug ] [ Designated as safety issue: Yes ]
  • Secondary endpoints for subjects who underwent PCI included TIMI major/minor and non TIMI bleeding, first occurrence or certain combination of major adverse cardiac events and death, and plasma drug concentration. [ Time Frame: To the end of the post treatment observation period (Day 121) ] [ Designated as safety issue: Yes ]
  • Secondary endpoints for subjects who underwent PCI included "clinically important" bleeding (composite incidence of intracranial bleeding and bleeding requiring blood transfusion and re-hospitalization). [ Time Frame: Discharge from hospital to end of post treatment observation period (Day 121) ] [ Designated as safety issue: Yes ]
  • Secondary endpoints for subjects who did not undergo PCI included incidence of TIMI major and minor bleeding, non TIMI bleeding, combination of first occurrence of death and major cardiovascular events, and atherothrombotic ischemic events. [ Time Frame: From the start of administration to the day of discharge ] [ Designated as safety issue: Yes ]
  • Secondary endpoints for subjects who did not undergo PCI included incidence of adverse events. [ Time Frame: To the end of the post treatment observation period (Day 121) ] [ Designated as safety issue: Yes ]
  • Secondary endpoints for subjects who did not undergo PCI, but who had coronary artery bypass graft (CABG), were bleeding, transfusions, and need for subsequent surgery. [ Time Frame: 8 +/- 2 hours after CABG ] [ Designated as safety issue: Yes ]
  • Secondary endpoints for subjects who did not undergo PCI included change in hs-CRP and expression of CD40 ligand. [ Time Frame: From baseline to the day of discharge ] [ Designated as safety issue: No ]
  • Secondary endpoints for subjects who did not undergo PCI included clinically significant bleeding. [ Time Frame: From discharge to the end of the post treatment observation period (Day 121) ] [ Designated as safety issue: Yes ]

Enrollment: 120
Study Start Date: December 2006
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SCH 530348 20 mg/1 mg
SCH 530348 20 mg loading dose + daily 1 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
Drug: SCH 530348
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
Drug: Aspirin
Once a day
Other Name: ASA, acetylsalicylic acid
Drug: Ticlopidine hydrochloride
Twice or three times a day
Experimental: SCH 530348 20 mg/2.5 mg
SCH 530348 20 mg loading dose + daily 2.5 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
Drug: SCH 530348
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
Drug: Aspirin
Once a day
Other Name: ASA, acetylsalicylic acid
Drug: Ticlopidine hydrochloride
Twice or three times a day
Experimental: SCH 530348 40 mg/1 mg
SCH 530348 40 mg loading dose + daily 1 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
Drug: SCH 530348
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
Drug: Aspirin
Once a day
Other Name: ASA, acetylsalicylic acid
Drug: Ticlopidine hydrochloride
Twice or three times a day
Experimental: SCH 530348 40 mg/2.5 mg
SCH 530348 40 mg loading dose + daily 2.5 mg maintenance dose + standard of care (Aspirin + Ticlopidine)
Drug: SCH 530348
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
Drug: Aspirin
Once a day
Other Name: ASA, acetylsalicylic acid
Drug: Ticlopidine hydrochloride
Twice or three times a day
Placebo Comparator: Placebo
Placebo loading dose + daily placebo maintenance dose + standard of care (Aspirin + Ticlopidine)
Drug: Placebo
Oral tablets; matching placebo for SCH 530348 loading and maintenance doses for 59 days
Drug: Aspirin
Once a day
Other Name: ASA, acetylsalicylic acid
Drug: Ticlopidine hydrochloride
Twice or three times a day

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Subjects who are planned to undergo PCI will be the target subjects.

    • A: Positive biomarkers [Elevated troponin I or CK-MB 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 subject 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00684203     History of Changes
Other Study ID Numbers: P04772
Study First Received: May 22, 2008
Last Updated: December 17, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Atherosclerosis
Myocardial Ischemia
Coronary Artery Disease
Infarction
Ischemia
Myocardial Infarction
Acute Coronary Syndrome
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Coronary Disease
Pathologic Processes
Necrosis
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Ticlopidine
Aspirin
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists

ClinicalTrials.gov processed this record on July 26, 2014