Dyslipidemia - Expert groups have identified low-density lipoprotein cholesterol (LDL-C) as the primary target for cholesterol lowering therapy because it is strongly associated with coronary heart disease (CHD) risk but, more importantly, clinical studies document that lowering LDL-C reduces the risk for major CHD events (Expert Panel NCEP ATP III 2001: De Backer et al 2003
Conditions
Interventions
Trade Name: CRESTOR
Product Name: rosuvastatin calcium
Pharmaceutical Form: Tablet
INN or Proposed INN: rosuvastatin calcium
CAS Number: CAS-287714-4
Concentration unit: mg milligram(s)
Concentration
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At Visit 1 (Week -6) For inclusion in the dietary lead-in phase, patients must fulfil all of the following criteria at Visit 1: 1. Provision of signed written informed consent 2. Male or female patients aged 18 years of age or older. 3. A history of CHD or a CHD risk equivalent, clinical evidence of atherosclerosis (definitions given in Appendix G) or a 10-year Framingham risk score of >20% for CHD, as described in NCEP ATP III guidelines 4. The patient must have a reasonable likelihood of attaining LDL-C values of = 130 mg/dL to =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: At Visit 1 (Week -6) Any of the following is regarded as a criterion for exclusion from the study: 1. Use of lipid lowering drugs and other prohibited concomitant medications from Visit 1 2. 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 3. Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have a positive serum pregnancy test (serum ß-HCG analysis) 4. Patients considered to be unstable by the Investigator after the following events (event within 8 to 12 weeks of study entry (Visit 1) at the Investigators discretion): a myocardial infarction, recent episode of unstable angina, myocardial revascularisation or a transient ischaemic attack or stroke. (These patients should be on a statin and should not be entered into a washout phase, therefore they are unsuitable for this study) 5. Severe congestive cardiac failure 6. Patients awaiting a planned myocardial revascularisation prior to Visit 1. (These patients require statin therapy and so a washout phase is not appropriate; therefore they are unsuitable for this study) 7. History of malignancy with the exception of resected basal cell or squamous cell carcinoma of the skin. Women with a history of cervical dysplasia will be permitted to enter the study provided they have 3 consecutive clear Papanicolaou (Pap) smears. (So that patients who are at risk of recurrence of malignancy requiring treatment are not included) 8. History of homozygous familial hypercholesterolaemia (the severity of hypercholesterolaemia in these patients usually dictates the need for individualised treatment regimens which can include phoresis) 9. History of alcohol or drug abuse within the last 5 years 10. Current active liver disease [alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) = 2 x upper limit of normal (ULN)] or severe hepatic impairment 11. Participation in another investigational drug study (including a previous rosuvastatin study) 1.5 x ULN (this is due to the relationship between myopathy and patients with hypothyroidism undergoing statin therapy) 16. Patients with unexplained creatine kinase (CK) within 3 months prior to enrolment in the dietary lead-in phase, defined as >1 x ULN 17. Serum creatinine >176 µmol/L or 2.0 mg/dL at Visit 2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. The percent change in LDL-C of rosuva 10mg/ezetimibe 10 vs simva 80mg/ezetimibe 10 mg 2. The percent change in HDL-C, TC, TG, nonHDL-C, ApoB, ApoA-1 of of rosuva 10mg/ezetimibe 10 vs simva 80mg/ezetimibe 10 mg 3. rosuva 20/ezetimibe 10 vs simva 40 mg/ezetimibe 10mg on the proportion of patients achieving lipid goals after 6 weeks. 4. rosuva 10/ezetimibe 10 vs simva 40 mg/ezetimibe 10mg on the proportion of patients achieving lipid goals after 6 weeks. 5. rosuva 20/ezetimibe 10 vs simva 80 mg/ezetimibe 10mg on the proportion of patients achieving lipid goals after 6 weeks. 6. rosuva 10/ezetimibe 10 vs simva 80 mg/ezetimibe 10mg on the proportion of patients achieving lipid goals after 6 weeks. 7. To assess rosuva 10mg and 20mg with ezetimibe 10mg vs the same dose of rosuva alone on the percent change in lab values ;Primary end point(s): Primary outcome variable: · Percentage LDL-C change from baseline to 6 weeks (mean of weeks 4 and 6) of combination therapy · Statistical significance of the following 3 comparisons will be tested simultaneously by a Hochberg procedure to control for multiple comparisons: 1. Rosuvastatin 20 mg + ezetimibe 10mg vs simvastatin 40 mg+ 10 mg ezetimibe. 2. Rosuvastatin 10 mg + ezetimibe 10mg vs simvastatin 40 mg+ 10 mg ezetimibe. 3. Rosuvastatin 20 mg + ezetimibe 10mg vs simvastatin 80 mg+ 10 mg ezetimibe ;Main Objective: The primary objective of this study is to evaluate the LDL-C lowering efficacy of rosuvastatin 10 mg and 20 mg in combination with ezetimibe relative to that of simvastatin in a fixed dose combination with ezetimibe. This objective has 3 specific components: 1. Percentage change from baseline in LDL-C for rosuvastatin 20mg in combination with ezetimibe 10mg vs simvastatin 40mg in combination with ezetimibe 10mg after 6 weeks combination therapy (mean value of 4 and 6 weeks of combination therapy will be used) 2. Percentage change from baseline in LDL-C for rosuvastatin 10mg in combination | — |
Countries
Lithuania, Netherlands
Outcome results
None listed