A Randomized, Double-Blind, Active-Controlled, Multicenter Study of Patients with Primary Hypercholesterolemia and High Cardiovascular Risk Who Are Not Adequately Controlled with Atorvastatin 10 mg: A Comparison of the Efficacy and Safety of Switching to Coadministration Ezetimibe and Atorvastatin Versus Doubling the Dose of Atorvastatin or Switching to Rosuvastati

Phase 3

Completed

Conditions: Primary Hypercholesterolemia and High Cardiovascular Risk
Patients with Primary Hypercholesterolemia and High Cardiovascular Risk

Registration Number: NL-OMON38112

Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 40

Inclusion Criteria

1. Men or women >18 and <80 years of age
2. Patient understands the study procedures, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
3. Patient is at high cardiovascular risk (determined by a preliminary Cardiovascular Risk Assessment usign historical lab values) and one of the following conditions are met:
- Naïve to lipid-lowering therapy (or have been off such therapy for >6 weeks pior to Visit 1) and has a historical LDL-C value approximately within the range noted in Appendix 6.4
or
-Currently taking stable dose of a statin, ezetimibe, or statin + ezetimibe combination listed below with LDL-C lowering efficacy equivalent to or less than atorvastatin 10 mg and has a historical LDL-C value approximately within the range noted in Appendix 6.4.: Simvastatin 10, 20mg, Pitavastatin 1mg, Atorvastatin 10mg, Pravastatin 10, 20, 40 mg, Fluvastatin 20, 40, 80 mg, Lovastatin 10, 20 ,40 mg, Ezetimibe 10 mg, Ezetimibe 10mg + Lovastatin 10 mg, Ezetimibe 10 mg + Pavastatin 10 mg, Ezetimibe 10 mg + Fluvastatin 20 mg.
4. Patient is willing to maintian an ESC/NCEP ATP III Therapeutic Lifestyle Changes (TLC) or similar cholesterol lowering diet for the duration of the study.
5. A female patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 accemtable methods of birth control for the duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, condom, vasectomy, and non-cyclical hormonal contraception.
6. Female patients who are receiving non-cyclical hormone therapy (including non-cyclical hormone replacement therapy or any estrogen antagonist/agonist, or non-cyclical oral contraceptives) if maintained on a stable dose and regimen for at least 8 weeks prior to Visit 1 and if willing to continue the same regimen throughout the study.

Exclusion Criteria

1. Patient is Asian
2. Patient has hypersensitivity or intolerance to ezetimibe, atorvastatin, rosuvastatin, or any component of these medications, or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin.
3. Patient routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week).
4. Female patient who is pregnant or lactating
5. Patient has been treated with any other investigational drug within 30 days of Visit 1 (Week 6)
6. Patient has any condition or situation which, in the opinion of the investigator, might have posed a risk to hte patient or interfere with participation in the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Hypothesis<br /><br>In patients with primary hypercholesterolemia and high cardiovascular risk with<br /><br>LDL-C >=100 mg/dL (2.59 mmol/L) and <=160 mg/dL (4.14 mmol/L):<br /><br>1)at the end of Phase I, coadministered ezetimibe 10 mg + atorvastatin 10 mg is<br /><br>superior to atorvastatin 20 mg with respect to the percentage reduction in<br /><br>LDL-C after 6 weeks of treatment among patients who are not adequately<br /><br>controlled with atorvastatin 10 mg prior to randomization.<br /><br>2)at the end of Phase I, coadministered ezetimibe 10 mg + atorvastatin 10 mg is<br /><br>superior to rosuvastatin 10 mg with respect to the percentage reduction in<br /><br>LDL-C after 6 weeks of treatment among patients who are not adequately<br /><br>controlled with atorvastatin 10 mg prior to randomization.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Hypothesis<br /><br>In patients with primary hypercholesterolemia and high cardiovascular risk with<br /><br>LDL-C >=100 mg/dL (2.59 mmol/L) and <=160 mg/dL (4.14 mmol/L):<br /><br>1)at the end of Phase II, coadministered ezetimibe 10 mg + atorvastatin 20 mg<br /><br>is superior to atorvastatin 40 mg with respect to the percentage reduction in<br /><br>LDL-C after 6 weeks of treatment among patients who are not adequately<br /><br>controlled with atorvastatin 10 mg prior to randomization and who are not<br /><br>adequately controlled with atorvastatin 20 mg during Phase I.<br /><br>2)at the end of Phase II, coadministered ezetimibe 10 mg + atorvastatin 20 mg<br /><br>is superior to rosuvastatin 20 mg with respect to the percentage reduction in<br /><br>LDL-C after 6 weeks of treatment among patients who are not adequately<br /><br>controlled with atorvastatin 10 mg prior to randomization and who are not<br /><br>adequately controlled with rosuvastatin 10 mg during Phase I.</p><br>