12-week Open-label, Phase IIIb Comparing Efficacy and Safety of Rosuvastatin (CRESTOR™) in Combination With Ezetimibe

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treatment of Rosuvastatin (CRESTOR™) or Simvastatin given as monotherapy or given in combination with Ezetimibe, will lower the Low Density Lipoprotein Cholesterol (LDL-C) in patients with Hypercholesterolaemia and Coronary Heart Disease (CHD) or a CHD Risk Equivalent, Atherosclerosis or a 10-year CHD Risk of >20%

Official Title
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A 12-week Open-label, Randomised, Parallel-group, Multicentre, Phase IIIb Study to Compare the Efficacy and Safety of Rosuvastatin (CRESTOR™) in Combination With Ezetimibe and Simvastatin in Patients With Hypercholesterolaemia and CHD

Conditions
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Hypercholesterolemia, Coronary Heart Disease, Atherosclerosis

Intervention / Treatment
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* Drug: Rosuvastatin (Crestor)
* Drug: Ezetimibe
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with with hypercholesterolaemia and CHD or a CHD risk equivalent, clinical evidence of atherosclerosis or a Framingham 10-year CHD risk score of >20 Patients will need to sign an informed consent before any visit procedures can be performed, including procedures for the optional genetic research and biomarker studies. Patients must be 18 years or older and will be asked to stop taking any current cholesterol-lowering medications. Dietary counselling will be provided which will include an overview of the Therapeutic Lifestyle Change (TLC) diet the patients will be asked to follow Exclusion Criteria: Use of lipid lowering drugs and other prohibited concomitant medications. History of statin-induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins), including rosuvastatin, simvastatin and/or a history of hypersensitivity to any components of ezetimibe. Patients considered to be unstable by their physician after the following events: a myocardial infarction, recent episode of unstable angina, myocardial revascularisation [percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG) surgery or another revascularisation procedure] or a transient ischaemic attack (TIA) or stroke and patients awaiting a planned myocardial revascularisation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Rosuvastatin (Crestor)|10mg and 20 mg|
|Drug: Ezetimibe|10 mg|
|Drug: Simvastatin|40mg and 80 mg|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks Combination Treatment | Percent change in LDL-C = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks Combination Treatment | Percent change in HDL-C = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in Total Cholesterol (TC) After 6 Weeks Combination Treatment | Percent change in TC = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in Triglycerides (TG) After 6 Weeks Combination Treatment | Percent change in TG = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in Non-high-density Lipoprotein Cholesterol (nonHDL-C) After 6 Weeks Combination Treatment | Percent change in nonHDL-C = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in Apolipoprotein B (ApoB) After 6 Weeks Combination Treatment | Percent change in ApoB = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in Apolipoprotein A1 (ApoA-1) After 6 Weeks Combination Treatment | Percent change in ApoA-1 = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in TC/HDL-C After 6 Weeks Combination Treatment | Percent change in TC/HDL-C = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in LDL-C/HDL-C After 6 Weeks Combination Treatment | Percent change in LDL-C/HDL-C = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in Non-HDL-C/HDL-C After 6 Weeks Combination Treatment | Percent change in non-HDL-C/HDL-C = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in ApoB/ApoA-1 After 6 Weeks Combination Treatment | Percent change in ApoB/ApoA-1 = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in High-sensitivity C-reactive Protein (Hs-CRP) After 6 Weeks Combination Treatment | Percent change in hs-CRP = (Combination treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward) | 
| Percent Change in LDL-C After 6 Weeks Monotherapy | Percent change in LDL-C = (Monotherapy treatment value - Baseline value)/Baseline value*100 | Mean of Weeks 4 and 6 on monotherapy (Last observation carried forward) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolaemia, Coronary Heart Disease (CHD), Atherosclerosis