E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety bleeding of 4 doses of apixaban as compared to placebo over a 26 week treatment period in selected subjects with recent (≤7 days) Acute Coronary Syndrome ACS . To determine the optimal dose and regimen of apixaban for use in a Phase 3 ACS trial. |
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E.2.2 | Secondary objectives of the trial |
The secondary safety objectives are to evaluate the incidence of cardiovascular and all-cause death, non-fatal myocardial infarction, severe recurrent ischemia and non-hemorrhagic stroke during the 30 days after discontinuation of therapy to assess the incidence of adverse events and abnormal clinical laboratory test results. The secondary efficacy objectives are to evaluate the incidence of the composite of cardiovascular death, non-fatal myocardial infarction, severe recurrent ischemia and non-hemorrhagic stroke through Week 26. to evaluate the incidence of the composite of all-cause death, non-fatal myocardial infarction, severe recurrent ischemia and non-hemorrhagic stroke through Week 26. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1 Signed written informed consent Target population 2 Recent 8804;7 days Acute Coronary Syndrome with a symptoms of myocardial ischemia chest pain, dyspnea, etc. lasting a total of at least 10 minutes And either b elevation in cardiac biomarkers troponin T or I or creatine kinase-MB above the upper limit of normal or c dynamic ST segment deviation depression or elevation of 8805;0.1 mV 1.0 mm 3 Clinically stable, receiving standard care for ACS, including antiplatelet therapy acetylsalicylic acid ASA 8804; 165 mg/day, with or without clopidogrel 75 mg/day, based on the choice of the treating physician 4 Either unknown coronary anatomy or 50 stenosis in at least one major epicardial coronary artery Age and Sex 5 Women who are not of childbearing potential i.e., who are postmenopausal or surgically sterile , and men, ages 18 or legal age of consent to 90. Women are considered surgically sterile only if they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy. Women are considered postmenopausal only if they have had amenorrhea for 8805; 12 consecutive months, or for women on hormone replacement therapy HRT , if they have a documented serum follicle stimulating hormone FSH level 35 mIU/mL. Plus 1 or more additional risk characteristics from the following 1 Age 8805; 65 years 2 Both elevation in cardiac markers and dynamic ST deviation 8805; 1 mm 3 Diabetes mellitus 4 MI within the last 12 months other than qualifying event 5 Cerebrovascular disease prior 3 months ischemic stroke; prior TIA or asymptomatic 70 stenosis in either internal carotid artery 6 Peripheral vascular disease claudication with decreased pulses, a prior peripheral revascularization procedure, or an ABI 0.9 7 Prior symptomatic CHF or a left ventricular ejection fraction 40 8 Non-revascularized multivessel CAD 8805;2 vessels 9 Mild or moderate renal insufficiency calculated CrCl 30-90 mL/min |
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E.4 | Principal exclusion criteria |
Sex and Reproductive Status 1 Women of child bearing potential a. Any female who has experienced menarche and who has not undergone successful surgical sterilization hysterectomy, bilateral tubal ligation or bilateral oophorectomy or is not postmenopausal defined as amenorrhea 12 consecutive months; or women on hormone replacement therapy HRT with documented serum follicle stimulating hormone FSH level 35 mIU/mL . Even women who are using oral, implanted or, injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods diaphragm, condoms, spermicides to prevent pregnancy or practicing abstinence or where partner is sterile e.g., vasectomy , should be considered to be of child bearing potential. b. Women who are pregnant or breastfeeding. c. Women with a positive pregnancy test on enrollment or prior to study drug administration. Target Disease Exceptions 2 Scheduled/planned cardiac catheterization, PCI, CABG or other invasive procedure planned in the 26 weeks following randomization Medical History and Concurrent Diseases 3 Persistent severe hypertension, defined as systolic blood pressure of 8805;180 mm Hg or diastolic pressure of 8805;110 mm Hg 4 Severe renal dysfunction calculated creatinine clearance 30 mL/min 5 Active bleeding or at high risk for bleeding e.g., cirrhosis of the liver, any history of intracranial hemorrhage 6 Known coagulopathy 7 Acute pericarditis or pericardial effusion 8 Recent stroke within the last 3 months 9 Prior New York Heart Association NYHA Class IV Physical and Laboratory Test Findings 10 Platelet count 8804;100,000/mm3 11 Hemoglobin 10 g/dL12 Hematocrit 30 Allergies and Adverse Drug Reactions 13 Inability to take aspirin due to allergy or intolerance Prohibited Therapies and/or Medications 14 Need for ongoing treatment with a parenteral or oral anticoagulant see Section 6.4.1 , eg, subjects with mechanical valves, warfarin eligible atrial fibrillation 15 Need for chronic 3 months daily NSAID or chronic high dose ASA use 325 mg/day Other Exclusion Criteria 16 Below the legal lower age country specific 17 Participation in another investigational drug or device study within the prior 30 days 18 Subjects who participated previously in this or any other study involving BMS-562247 19 Any condition which, in the opinion of the Investigator, may pose a significant hazard to the subject if he or she is enrolled in the trial 20 Subject inability to follow the protocol 21 Prisoners or subjects who are compulsorily detained involuntarily incarcerated for treatment of either a psychiatric or physical e.g., infectious disease illness must not be enrolled into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety outcome for this trial is the composite of major bleeding and clinically significant non-major bleeding occurring through the end of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |