Coronary Artery Disease MedDRA version: 8.1 Level: PT Classification code 10011078
Conditions
Interventions
Product Code: E5555
Pharmaceutical Form: Film-coated tablet
CAS Number: 474550-69-1
Current Sponsor code: E5555
Other descriptive name:
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 45 – 80 years, inclusive • Males or Females (women of child-bearing potential must use adequate protection) • Confirmed coronary artery disease defined as one of the following: - Post-ACS or MI or Post PCI (greater than 4 weeks) or - CABG (greater than 12 weeks) or - Angina pectoris with documented (ECG or imaging study) ischemia or - Angiographically documented lesion occluding =70% of a coronary vessel And at high risk as defined by one or more of the following: • Screening hsCRP = 3.0 mg/L • History of diabetes mellitus under Rx treatment • Documented history of peripheral arterial disease • Documented history of Thrombo-embolic TIA or stroke greater than 1 year prior to screening • Documented history of Carotid artery disease All subjects must be receiving low-dose (75-325 mg) aspirin and or clopidogrel 75 mg once daily. Ticlopidine 250mg twice daily with or without low dose aspirin once daily is also allowed. These medications must be taken for at least 1 month prior to screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Unwilling or unable to provide informed consent •History of acquired or congenital bleeding disorder, coagulopathy, or platelet disorder • Recent trauma or major surgery in the past 30 days prior to Screening • Evidence of active pathological bleeding at screening or history of bleeding (such as gastrointestinal or genitourinary) within the 6 months prior to Screening, unless the cause has been definitely corrected • History of intracranial bleeding (eg, hemorrhagic stroke, subdural hematoma, subarachnoid hemorrhage) or history of hemorrhagic retinopathy • History of ischemic stroke or transient ischemic attack within the past year prior to Screening or known structural cerebral vascular lesion (eg, arterial venous malformation, aneurysm) • Hematological abnormalities: INR >1.5 or PTT >1.5 X ULN, Platelet count 3 x ULN or Total Bilirubin >1.5 x ULN (unless the abnormal bilirubin level is secondary to Gilbert’s syndrome) • Documented presence of rheumatologic or autoimmune diseases requiring continuous treatment with anti-inflammatory agents • Significant renal impairment, defined as creatinine clearance <30 mL/min • History of cancer (other than basal cell carcinoma of the skin, cervical carcinoma in situ, or low-grade prostate cancer), unless adequately treated with no evidence of disease recurrence for at least 2 years • Recent (within 14 days prior to Baseline Visit) significant infection or history of chronic infections with a recurrence <14 days prior to the Screening Visit and/or requiring continuous antibiotic treatment • Use of any of the following drugs in the 30 days prior to Screening and for the duration of the study: - Oral anti-thrombotics other than low dose aspirin (daily aspirin dose of 325 mg or lower) and/or clopidogrel (75 mg) and/or ticlopidine (250 mg bid) - Anticoagulants (eg, coumadin, warfarin) - Fibrinolytics (eg, TPA, streptokinase, urokinase) - NSAIDs, other than occasional use - COX-2 inhibitors, other than occasional use - Potent CYP (global) 3A4 inhibitors - Selected CYP 2D6 substrates - Herbals with antiplatelet properties: Gingko biloba, Horse chest
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of E5555 in patients with coronary artery disease.;Secondary Objective: To determine the effect of E5555 on (a) the incidence of major adverse cardiovascular effects (MACE) (cardiovascular death, myocardial infarction, stroke and refractory ischemia) and b) platelet aggregation inhibition (in qualified sites in subjects willing to take part in this component of the study). The exploratory objective being pursued is to determine the effect of E5555 on the endovascular inflammatory processes that are believed to be integral to the pathogenesis of coronary artery disease. In addition, the pharmacokinetics of E5555 and its metabolites will be determined. Qualified sites will conduct comprehensive plasma sample collection for measurement of levels of E5555 and its metabolites to evaluate the relationship between E5555 pharmacokinetics and pharmacodynamics. ; Primary end point(s): The primary goal of this study is to assess the effect of E5555 on general safety and tolerability in high risk patients with coronary artery disease especially the risk of bleeding. The primary outcome will be the proportions of subjects with CEC-adjudicated bleeds. Cross-classification tables of CEC-adjudicated major bleeds vs treatment groups will be created. Safety and tolerability will be determined by comparison of SAEs, treatment emergent AE, treatment emergent abnormal laboratory values, and ECG changes in the three treatment groups with those in the placebo group. The secondary endpoint used to assess efficacy issues between the treatment groups will be the proportion of subjects with CEC-adjudicated MACE events. Exploratory parameters: To determine possible anti-inflammatory effects of E5555, the inflammatory marker hsCRP will be measured at Baseline and Weeks 2, 4, 12, 16, 20, 24, and 28. Summary estimates of other biomarkers may be created to explore the efficacy di | — |
Countries
Belgium, Czech Republic, Germany, Hungary, Netherlands, United Kingdom
Outcome results
None listed