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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
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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 evaluate the LDL-C lowering efficacy of the addition of ezetimibe (10 mg) to rosuvastatin (5 or 10 mg) (pooled across doses) compared with doubling the baseline dose of rosuvastatin (pooled) in patients with primary hypercholesterolemia at moderately high or high risk for CHD, who are treated with rosuvastatin (5 or 10 mg) alone and not at their NCEP ATP III LDL-C goal. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the LDL-C lowering efficacy of the addition of ezetimibe (10 mg) to the rosuvastatin 5 mg compared with rosuvastatin 10 mg in patients with primary hypercholesterolemia at moderately high or high risk for CHD, who are treated with rosuvastatin 5 mg alone and not at their NCEP ATP III LDL-C goal. 2. To evaluate the LDL-C lowering efficacy of the addition of ezetimibe (10 mg) to rosuvastatin 10 mg compared with rosuvastatin 20 mg in patients with primary hypercholesterolemia at moderately high or high risk for CHD, who are treated with rosuvastatin 10 mg alone and not at their NCEP ATP III LDL-C goal. 3. In patients with primary hypercholesterolemia at moderately high or high risk for CHD, who are treated with rosuvastatin 5 or 10 mg alone and not at their NCEP ATP III LDL-C goal:
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women between 18 and 79 years of age. • Patient is currently taking a stable dose of lipid-lowering agents listed below and the LDL-C prescreen value is within the range noted in Appendix 6.8. Simvastatin 5 mg, 10 mg, 20 mg, 40 mg, 80 mg* Atorvastatin 10 mg, 20 mg, 40 mg* Rosuvastatin 5 mg, 10 mg Pravastatin 10 mg, 20 mg, 40 mg Fluvastatin 20 mg, 40 mg, 80 mg Lovastatin 10 mg, 20 mg, 40 mg, 80 mg Ezetimibe 10 mg Ezetimibe 10 mg + Pravastatin 10 mg Ezetimibe 10 mg + Simvastatin 10 mg* Ezetimibe + Fluvastatin 10 /20 mg or 10/40 mg Ezetimibe + Lovastatin 10/10 mg or 10/20 mg
• Patient is moderately high risk (patients with multiple (2+) risk factors that confer a 10-year risk for CHD of 10 to 20% as estimated from Framingham risk scores): Visit 2 LDL-C ≥100 mg/dL but ≤160 mg/dL (2.6 and 4.2 mmol/L) -or- Patient is high risk without atherosclerotic vascular disease (patients with CHD risk equivalents: diabetes mellitus or multiple (2+) risk factors that confer a 10-year risk for CHD >20% as estimated from Framingham risk scores): Visit 2 LDL-C ≥100 mg/dL but ≤160 mg/dL (2.6 and 4.2 mmol/L) -or- Patient is high risk with atherosclerotic vascular disease (patients with established CHD; or patients with CHD risk equivalents: diabetes mellitus or multiple (2+) risk factors that confer a 10-year risk for CHD >20% as estimated from Framingham risk scores AND other atherosclerotic vascular disease*: Visit 2 LDL-C ≥70 mg/dL but ≤160 mg/dL (1.8 and 4.2 mmol/L)
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E.4 | Principal exclusion criteria |
• Patient has hypersensitivity or intolerance to ezetimibe, or rosuvastatin or any component of these medications, or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin. • Patient has uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mm Hg or diastolic >100 mm Hg. Investigators are encouraged to maximize blood pressure control according to current guidelines prior to randomization. • Patient has diabetes mellitus (Type 1 or 2) that is poorly controlled (HbA1c ≥8.5% at Visit 1 or newly diagnosed (within 3 months of Visit 1) and/or patient has recent history of repeated hypoglycemia or unstable glycemic control, or has had a change in treatment (changes in dosage or addition of new therapy) of antidiabetic pharmacotherapy or change of ±10 units of insulin, within 2 months of Visit 1. • Current use of cyclosporine, itraconazole, lopinavir or ritonavir • Current use of fibrates, niacin, or resins
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E.5 End points |
E.5.1 | Primary end point(s) |
• Percent change from baseline in LDL-C |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 6 |
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 | 8 |