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 | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020603 |
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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 compare the efficacy of ezetimibe/simvastatin 10/20 mg when administrated daily versus doubling the dose of simvastatin to 40 mg in reducing the concentration of LDL-C at endpoint after 6 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of ezetimibe/simvastatin 10/20 mg when administrated daily versus doubling the dose of simvastatin to 40 mg at endpoint after 6 weeks of treatment with respect to 1. the percentage of subjects who achieve the target LDL-C goal as defined by the NCEP III guidelines 2.6 mmol/L; 100 mg/dL . 2. percent change from baseline in the concentrations of total cholesterol, HDL-C , triglycerides and C-reactive protein. 3. safety and tolerability. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Subjects must have documented coronary heart disease CHD . For the purposes of this study, CHD will include one or more of the following features documented stable angina with evidence of ischemia on exercise testing ; history of myocardial infarction; history of percutaneous coronary intervention primarily PCI with or without stent placement ; symptomatic peripheral vascular disease claudication ; documented history of atherothrombotic cerebrovascular disease; and/or documented history of unstable angina or non-Q wave myocardial infarction. 2. Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent. 3. Subjects must be 18 years and 75 years of age. 4. Subjects must have an LDL-C concentration 2.6 mmol/L 100 mg/dL to 4.1 mmol/L 160 mg/dL using the Friedewald calculation see Section 8.8 available at the time of randomization Visit 3 Baseline Visit . 5. Subjects must have triglyceride concentrations of 3.99 mmol/L 350 mg/dL at Visit 3 Baseline Visit . 6. Subject must be currently taking simvastatin 20 mg daily and by history has taken 80 of daily evening doses for the 6 weeks prior to Visit 3 Baseline Visit . 7. Subjects must have liver transaminases ALT, AST 50 above the upper limit of normal, with no active liver disease, and CK 50 above the upper limit of normal at Visit 3 Baseline Visit . 8. Clinical laboratory tests CBC, blood chemistries, urinalysis must be within normal limits or clinically acceptable to the investigator at Visit 3 Baseline Visit . 9. Subjects must have maintained a cholesterol lowering diet and exercise program for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study. 10. Subjects must report a stable weight history for at least 4 weeks prior to entry into study at Visit 3 Baseline Visit . 11. Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study. 12. Women of childbearing potential includes women who are less than 1 year postmenopausal and women who become sexually active must be using an acceptable method of birth control e.g., hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide or be surgically sterilized e.g., hysterectomy or tubal ligation . 13. Subjects must be free of any clinically significant diseases other than hyperlipidemia or coronary heart disease that would interfere with study evaluations. 14. Subjects must understand and be able to adhere to the dosing and visit schedules, and must agree to remain on their cholesterol-lowering diet and their exercise regimen for the duration of the study. |
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E.4 | Principal exclusion criteria |
1. Subjects whose body mass index BMI weight kg /height2 m is 35 Kg/m2 at Visit 3 Baseline Visit . 2. Subjects who consume 14 alcoholic drinks per week. A drink is a can of beer, glass of wine, or single measure of spirits . 3. Any condition or situation which, in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study. 4. Women who are pregnant or nursing. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the efficacy of ezetimibe/simvastatin 10/20 mg when administrated daily versus doubling the dose of simvastatin to 40 mg in reducing the concentration of LDL-C at endpoint after 6 weeks 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 | 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 | Information not present in EudraCT |
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) | No |
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 | 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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 0 |
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 | 0 |