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

Official Title: “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”

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%

Intervention(s) in this Clinical Trial

• Drug: Rosuvastatin (Crestor)
  • 10mg and 20 mg
• Drug: Ezetimibe
  • 10 mg
• Drug: Simvastatin
  • 40mg and 80 mg

Primary Measures

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No

Secondary Measures

• Percent Change in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in Total Cholesterol (TC) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in Triglycerides (TG) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in Non-high-density Lipoprotein Cholesterol (nonHDL-C) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in Apolipoprotein B (ApoB) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in Apolipoprotein A1 (ApoA-1) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in TC/HDL-C After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in LDL-C/HDL-C After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in Non-HDL-C/HDL-C After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in ApoB/ApoA-1 After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in High-sensitivity C-reactive Protein (Hs-CRP) After 6 Weeks Combination Treatment
  • Time Frame: Mean of Weeks 4 and 6 on combination therapy (Last observation carried forward)
    Safety Issue?: No
• Percent Change in LDL-C After 6 Weeks Monotherapy
  • Time Frame: Mean of Weeks 4 and 6 on monotherapy (Last observation carried forward)
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: AstraZeneca Industry

Overall Clinical Trial Officials and Contacts

Christie M Ballantyne, MD FACP FACC Principal Investigator Centre for Cardiovascular Disease Prevention  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00525824

Study ID Number: D356FC00003

ClinicalTrials.gov Identifier: NCT00525824

Health Authority: United States: Food and Drug Administration