E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
MedDRA Classification |
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 this clinical trial is to demonstrate whether or not the fixed combination torcetrapib/atorvastatin can incrementally reduce the risk for future occurrence of major cardiovascular disease events (MCVE), when compared to atorvastatin alone, in subjects with coronary heart disease (CHD) or risk equivalents | |
E.2.2 | Secondary objectives of the trial | Secondary objectives will include examining the effect of torcetrapib/atorvastatin over that of atorvastatin alone on the following: 1. The time to first occurrence of the following clinical endpoints:· - Major CHD events composite (defined as CHD death and nonfatal MI)· - MCVE, coronary revascularization procedures, and PVD composite - Stroke (fatal and nonfatal) and (TIA) composite - Major CHD events, stroke (fatal and nonfatal), and TIA composite - All cause mortality 2. Change from baseline in LDL-C and HDL-C. | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria | Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial 1.Subjects with high risk of CVD events defined as any of the following: a. Prior myocardial infarction in which the most recent event occurred 1 month (30 days) to 60 months prior to the screening visit. b. Previous cardiac revascularization procedure prior to screening (see protocol for more details) c. Pre existing atherosclerotic CHD (documented acute coronary syndrome including unstable angina) in which the most recent event occurred 1 month (30 days) to 60 months prior to the screening visit. (see protocol for more details) d. Pre existing symptomatic carotid artery disease (documented prior stroke defined as persistent brain deficit lasting more than 24 hours with a demonstrable lesion by CT or MRI scan) at least one month (30 days) prior to screening. e. Pre existing PVD; documented as either a peripheral intervention [at least one month (30 days) prior to screening] or ankle/brachial index (ABI) <0.9. f. Prior diagnosis of type 2 diabetes including subjects currently on hypoglycemic agents or insulin, and/or according to American Diabetes Association (ADA) criteria. 2. Subjects eligible for statin (HMG CoA reductase inhibitor) treatment defined as: a. On a statin or other prescription lipid altering treatment at screening, or b. LDL C ³100 mg/dL (2.6 mmol/L) if not on a prescription lipid altering treatment at screening. | |
E.4 | Principal exclusion criteria | Subjects presenting with any of the following will not be included in the trial: 1. Women who are pregnant, lactating, or who are planning to become pregnant Women of childbearing potential who have not successfully been using acceptable contraceptive methods over the previous 3 months (eg, hormonal contraception, intrauterine device, barrier method plus spermicide). 2. Subjects at Visit 1 who are not on prior prescription lipid-altering treatment, and have an LDL C of <100 mg/dL (2.6 mmol/L). 3. Subjects who at the final atorvastatin only run in visit (ie, subjects are on 80 mg atorvastatin daily), fail to reach the target LDL C of <100 mg/dL (2.6 mmol/L) 4. Subjects who have participated in long term (³3 years) cardiovascular endpoint trials anytime within the 12 months prior to screening/Visit 1. 5. Subjects or are planned after randomization a coronary angioplasty, CABG, other cardiovascular surgery (eg, valve replacement), or other peripheral intervention; or experiencing a CVD event (eg, MI, stroke) within 30 days (exclusive) of the screening visit or during the atorvastatin only run in period. 6. Subjects with severe pre existing CHD that limits their expected ability to complete the trial or their life expectancy (please see protocol for further details). 7. Subjects with uncontrolled hypertension, defined as an average SBP >140 mmHg or an average diastolic blood pressure (DBP) >90 mmHg, at baseline. Subjects with an average SBP >140 mmHg or DBP >90 mmHg at screening or any run in visit (Visits 2 6) should receive appropriate treatment for hypertension. 8. Fasting triglycerides >500 mg/dL (5.6 mmol/L) at Visit 1 or 2. 9. Subjects receiving the following concomitant lipid-altering therapy ( non statins and statins) or therapies affecting LDL-C, HDL-C and TG at Visit 1: 10. Subjects taking any drugs known to be associated with an increased risk of myositis in combination with HMG CoA reductase inhibitors. 11.Subjects with any other medical condition or laboratory abnormality prior to randomization, which in the opinion of the principal investigator could affect subject safety, preclude evaluation of response, or render unlikely that the subject would complete the study, including but not limited to: a. Subjects with uncontrolled diabetes mellitus; b. Subjects with renal disease c. Subjects with uncontrolled hypothyroidism defined as a TSH >2 times the ULRR at Visit 1; d. Subjects with any active hepatobiliary disease (including cirrhosis), serologic evidence of past or active hepatitis B or hepatitis C infection, or an AST or ALT >2 times the ULRR, alkaline phosphatase >1.5 times the ULRR with elevated liver isoform of alkaline phosphatase or total bilirubin >1.5 times the ULRR at Visit 1 or 2; e. Subjects with unexplained serum CK >3 times the ULRR at Visit 1 or 2 (eg, not due to recent trauma, intramuscular injections, heavy exercise). A repeat CK >3 times ULRR in the absence of conditions explaining CK elevation is exclusionary; f. Subjects with any prior history of malignancy. g. Subjects with gastrointestinal disease limiting drug absorption or partial ileal bypass, gastric stapling, or gastric binding; h. Subjects with alcohol and/or any other drug abuse or dependence. | |
E.5 End points |
E.5.1 | Primary end point(s) | Time to first occurrence of an MCVE defined as:· - CHD death, - Nonfatal myocardial infarction (MI), or· - Stroke (fatal and nonfatal) | |
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 | 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) | No |
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) | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | |
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 | Study completion is scheduled to occur when 984 primary endpoints have occurred | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 10 |