E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with Acute Coronary Syndromes (ACS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
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 |
The primary objective of the study is to determine whether 16 weeks of treatment with A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the hazard of the first occurrence of the combined endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or documented unstable angina with objective evidence of ischemia requiring hospitalization. |
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E.2.2 | Secondary objectives of the trial |
A secondary objective of the study is to determine whether A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the occurrence of the hazard of the combined endpoint of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke or documented unstable angina with objective evidence of ischemia requiring hospitalization or multiple occurrences of the non-fatal components of the composite primary endpoint. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women ≥40 years of age 2. Written informed consent from the subject 3. A diagnosis of unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI) 4. All subjects (unstable angina, NSTEMI, or STEMI) must have the presence of at least one of the following risk factors: i. Diabetes Mellitus ii. Presence of any specified (see protocol) characteristics of metabolic syndrome. iii. history of cerebrovascular disease (stroke or TIA) or iv. history of peripheral vascular disease or v. previous CABG or vi. previous documented myocardial infarction or vii. previous coronary revascularization or 5. Subjects must be randomized within ≤96 hours of hospital admission for the index event, or if already hospitalized, within ≤96 hours of index event diagnosis 6. Revascularization, if required or planned, must occur prior to randomization. |
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E.4 | Principal exclusion criteria |
1. Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening. 2. Subjects treated for cancer within the previous 5 years except for skin basal cell carcinoma or carcinoma in situ of the cervix, with measures other than a minor, complete surgical excision or radiation therapy (e.g. chemotherapy) 3. The presence of any severe liver disease with cirrhosis, active hepatitis, active chronic hepatitis, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN, biliary obstruction with hyperbilirubinemia (total bilirubin >2 x ULN) 4. Active cholecystitis, gall bladder symptoms, or any hepatobiliary abnormalities 5. The presence of severe renal impairment (creatinine clearance [CrCl] <30 mL/min or creatinine >3 x ULN), nephrotic syndrome, or subjects undergoing dialysis 6. Uncontrolled diabetes mellitus (known hemoglobin A1c [HbA1c] >11% within the last 1 month prior to Screening) 7. Females who are nursing, pregnant, or intend to become pregnant during the time of the study, or females of childbearing potential who have a positive pregnancy test during screening evaluation. Women of child-bearing potential must also use a reliable method of birth control during the study and for 1 month following completion of therapy. A reliable method for this study is defined as one of the following: oral or injectable contraceptives, intrauterine device (IUD), contraceptive implants, tubal ligation, hysterectomy, a double barrier method (diaphragm with spermicidal foam or jelly, or a condom). 8. Subjects who have a history of alcohol or drug abuse within 1 year of study entry 9. Subjects living too far from participating center or unable to return for follow-up visits 10. Subjects who in the opinion of the Investigator are a poor medical or psychiatric risk for therapy with an investigational drug, are unreliable, or have an incomplete understanding of the study which may affect their ability to take drugs as prescribed or comply with instructions 11. Known human immunodeficiency virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), or tuberculosis infection 12. Acute bacterial, fungal or viral infection 13. Subjects currently taking drugs that are potent inhibitors of cytochrome P450 unless they can be withdrawn 14. Subjects with New York Heart Association (NYHA) Class III or IV heart failure, or if known, left ventricular ejection fraction (LVEF) <30% 15. Subjects with moderate or severe aortic stenosis, aortic regurgitation, mitral stenosis or mitral regurgitation 16. Ventricular arrhythmias requiring chronic drug treatment or implantable cardioverter-defibrillator (ICD) 17. Subjects with no stenosis or stenosis <50% on angiography, if known 18. Subjects with a pacemaker or persistent left bundle branch block (LBBB) 19. Fasting triglyceride levels of ≥400 mg/dL (4.5 mmol/L) 20. Subjects who have a history of statin intolerance or a significant myopathy or rhabdomyolysis with any lipidaltering drugs 21. Subjects currently treated with the maximum labeled dose of a statin and not at LDL-C target for their level of risk as defined by NCEP ATP III |
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E.5 End points |
E.5.1 | Primary end point(s) |
The overall primary objective of the study is to determine whether 16 weeks of treatment with A-002 plus atorvastatin and standard of care is superior to placebo plus atorvastatin and standard of care for reducing the hazard of the first occurrence of the combined endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or documented unstable angina with objective evidence of ischemia requiring hospitalization. |
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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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 40 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 | Yes |
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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Following the last patient-last dose, the completion of the 6-month follow-up of this last patient represents the end of 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |