| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Elderly Patients With Hypercholesterolemia at Moderately High Risk and High Risk for Coronary Heart Disease. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10028600 |
|
| 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 assess the percent change from baseline in LDL-C levels after 12 weeks of treatment at the usual start dose comparisons of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 mg, and ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg, and at the alternative start dose comparison of ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg. |
|
| E.2.2 | Secondary objectives of the trial |
1) To assess the percentage of patients who achieve an LDL-C of < 70 mg/dL (1.81 mmol/L) after 12 weeks of treatment at the usual start dose comparisons of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 mg, and ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg, and at the alternative start dose comparison of ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg.
2) To assess the percentage of patients achieving an LDL-C level (<100 mg/dL (2.59 mmol/L) for both patients at high risk for CHD without atherosclerotic vascular disease and moderately high risk for CHD, and <70 mg/dL (1.81 mmol/L) for patients at high risk for CHD with atherosclerotic vascular disease) after 12 weeks of treatment at the usual start dose comparisons of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 mg, and ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg, and at the alternative start dose comparison of ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Patients with screening values/findings outside the ranges described in the protocol may, at the discretion of the investigator, have one repeat determination performed and if the repeat value satisfies the criterion they may continue in the screening process. Only the specific out of range value/finding should be repeated (not the entire panel, except when a specific lipid test needs to be repeated, then the entire lipid panel should be repeated).
1. Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
2. Patient is a male or post menopausal female and ≥65 years of age on the day of signing informed consent.
3. Patient is willing to maintain a NCEP Therapeutic Lifestyle Changes (TLC)/ADA or similar cholesterol lowering diet for the duration of the study.
4. Female patients who are receiving non cyclical hormone therapy (including non cyclical hormone replacement therapy or any estrogen antagonist/agonist) have been maintained on a stable dose and regimen for at least 8 weeks prior to Visit 1 (Week -3) and patient is willing to continue the same regimen throughout the study.
5. Patient meets one of the following criteria:
o Therapy naïve patients who are at high risk for CHD with established coronary and other atherosclerotic vascular disease or,
Note: Established atherosclerotic vascular disease includes history of myocardial infarction, stable angina, coronary artery procedures (angioplasty or bypass surgery) or evidence of clinically significant myocardial ischemia. Other atherosclerotic vascular disease includes clinical manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]).
Therapy naïve is defined as not being treated with a lipid lowering agent within 6 weeks (8 weeks if a fibrate) prior to Visit 2 (Week -1).
o Therapy naïve patients who are at high risk for CHD without atherosclerotic vascular disease who have diabetes or,
o Therapy naïve patients who are at high risk for CHD without atherosclerotic vascular disease or diabetes with ≥2 risk factors and a 10-year risk for CHD >20% (as determined by the Framingham calculation, see Appendix 6.4) or,
o Therapy naïve patients, or patients rendered naïve by the appropriate prior washout, who are at moderately high risk for CHD with ≥2 risk factors and a 10-year risk for CHD 10-20% (as determined by the Framingham calculation, see Appendix 6.4).
Note: Patients rendered naïve is defined as washed out of a lipid lowering agent for 6 weeks (8 weeks if a fibrate) prior to Visit 2 (Week -1). |
|
| E.4 | Principal exclusion criteria |
1. Patient weighs < 100 lbs (45 kg).
2. Patient has hypersensitivity or intolerance to ezetimibe, simvastatin or atorvastatin or any component of these medications, or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin.
3. Patient routinely consumes more than 2 alcoholic drinks per day.
4. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
5. Patient has taken torcetrapib alone or in combination and the last dose was within 1 year of Visit 1.
Note: To participate in the study, patients who previously participated in a torcetrapib trial must provide documentation that he/she did not receive torcetrapib or that the last dose of torcetrapib was greater than 1 year of Visit 1.
6. Patient has exclusionary laboratory values at Visit 1 (Week -3) as listed in the table below:
Laboratory Test Exclusionary Value
liver transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) > 1.5 X ULN with no active liver disease
Creatine kinase (CK) > 2 X ULN
7. Patient’s triglycerides (TG) are > 350 mg/dL (3.95 mmol/L) at Visit 2.
8. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia, such as hypothyroidism or hyperthyroidism).
Note: A patient with hyper or hypothyroidism is defined by a TSH below the central laboratory's lower limit of the normal reference range or > 20% above the upper limit of the normal reference range at Visit 1. For patients receiving thyroid hormone, there is no lower TSH threshold for entry and the patient must be on a stable dose for ≥6 weeks before the randomization visit. For patients whose TSH is above the entry criteria, thyroid hormone therapy may be adjusted or initiated provided there is time to stabilize the patient and still meet the enrollment timelines. One redraw will be allowed if the original TSH value is less than 40% above or below the reference range, but the patient must meet the criterion upon redraw.
9. Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is the mean percent change from baseline (Visit 3) in LDL-C after 12 weeks of treatment. |
|
| 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 | 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) | 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 | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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