E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016205 |
E.1.2 | Term | Familial hyperlipidaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet) compared with Simvastatin 40mg in stablilized acute coronary syndrome (ACS) subjects. Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of CV death, major coronary events, and non-fatal stroke. Major coronary events include non-fatal MI, documented unstable angina that requires admission into a hospital and all coronary revascularization with either PCI or CABG occuring at least 30 days after randomization. Only revasculatiztion events that occur after the first 30 days of treatment will be considered as Clinical Endpoint events, in order to focus on events that can be expected to be affected by treatment and are unrelated to the initial ACS event. |
|
E.2.2 | Secondary objectives of the trial |
a. Evaluate the clinical benefit of Ezetimibe/Simvastatin Combination compared to Simvastatin on the occurance of the composite endpoint of death due to all causes, major coronary events and non-fatal stroke.
b. Evaluate the clinical benefit of Ezetimibe/Simvastatin Combination compared to Simvastatin on the occurance of the composite endpoint of death due to coronary heart disease, non fatal MI, and urgent coronary revascularization with either PCI or CABG occurring at least 30 days after randomization.
c. Evaluate the clinical benefit of Ezetimibe/Simvastatin Combination compared to Simvastatin on the occurance of the composite endpoint of CV death, non fatal MI, Unstable angna requiring hospitalization, all and revascularization at least 30 days after randomization and Non-fatal stroke |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
High-risk ACS NSTE-ACS & STEMI subjects meeting the following conditions:
1. NSTE-ACS subjects meeting the following definition:
a. Clinically stable NSTE-ACS subjects participating in EARLY ACS Study (P03684) that do not go on to have CABG will be eligible if enrolled within 10 days of their hospitalization.
b. Clinically stable NSTE-ACS subjects not participating in EARLY ACS study who meet the following criteria will be eligible to enroll within 10 days of their hospitalization: Experience symptoms of cardiac ischemia at rest lasting at least 10 min within 24 hrs of hospitalization, at least 50yrs of age, and have 1 of the following: ECG changes in at least 2 contiguous leads characterized by either ST depression or transient ST elevation, elevation in cardiac enzymes, DM, History of MI, History of PAD, History of CVD, History of CABG at least 3 yrs prior,or multivessel documented CAD.
2. Clinically stable STEMI subjects maybe enrolled within 10 days of their hospitalization if they meet the following criteria: Experience symptoms of cardiac ischemia at rest with at least one episode lasting at least 30 minutes in conjunction with hospitalization and have ECG changes in at least 2 contiguous leads characterized by ST elevation or Qwaves or LBBB, have elevation in cardiac enzymes and the presences of anterior infarction or at least 50yrs of age.
3. LDL-C criteria: Lipid therapy naive subjects LDL-C must be at least 1.3 mmol/Land less than or equal to 2.6 mmol/L, Subjects on statin LDL-C must be at least 50 and less than or equal to 100 mg/dl.
4. Fasting Plasma Triglyceride must be less than or equal to 4.0 mmol/L.
5. New
Subjects, in whom PCI is plannedas management, should be randomized following PCI and within the 10 days period after initial hospitalization for quality event. Staged PCI is allowed , butneeds to be completed within 30 days of randomization. |
|
E.4 | Principal exclusion criteria |
1. Subject who is clinically unstable. A subject is considered clinically unstable if he/she displays any of the following spontaneous events for 24 hours prior to Screening-Randomization:
a. Hemodynamic events: Hypotension, Pulmonary edema/CHF, Acute mitral regurgitation, Acute ventricular septal defect.
b. Ischemic events: stroke, recurrent sx of cardiac ischemica.
c Arrhythmic events: Ventricular fibrillation, Sustained ventricular tachycardia, complete heart block, High grade second degree heart block
2. Subject requiring the following concomitant medications that cannot be discontinued:statins,ezetimibe, fusid acid, torcetrapib within 1 year prior to randomization, cyclosporine, diltiazem, danazol, amiodarone, verapamil, niacin, fibrates as concomitant medication or any of the potent CYP3A4 inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin and Telithromycin, HIV protease inhibitors, nedazodone
3. Pregnant or lactating woman, or intenting to become pregnant
4. Active liver disease or persistent unexplained serum transaminase elevation
5. History of alcohol or drug abuse,
6. History of intolerance or hypersensitivity to statin or ezetimibe
7. Discontinuation of existing lipid lowering regimen poses a risk to the subject
8. Subject is receiving statin therapy with an LDL-C lowering potency greater than simvastatin 40mg
9. Prior enrollment in this current study under Protocol P04103
10. Subjects who undergo CABG in response to qualifýing event
11. Patients with calculated creatinine clearance (CrCl)< 30 mL/mit or dialysis within30 days
12. Subjects participating in clinical research of approved therapy being administered according to the therapy's labeled use are NOT to be excluded.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the time from randomization until the first occurrence of one of the following: CV death, major coronary event (non-fatal MI, documented unstable angina that requires admission into a hospital, all coronary revascularization with either PCI or CABG occuring at least 30 days after randomization), or non-fatal stroke. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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 |
|
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
|
The planned termination of the study will occur after all 18,000 subjects have been followed for a minimum of 2.5 years and a primary endpoint event has been documented in at least 5250 subjects. if at least 5250 subjects do not have at least one documented primary endpoint event with 2.5 years of the completion of enrollment, the study will continue until this number of events has accumulated. It is anticipated that the whole study duration will be approximately 8 years. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
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 | 8 |
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 |