Official Title: “A Multicenter, Double-Blind, Randomized Study to Evaluate the Lipid-Altering Efficacy, Safety, and Tolerability of Ezetimibe Coadministered With Simvastatin Versus Simvastatin Monotherapy in African-American Subjects With Primary Hypercholesterolemia”

The purpose of this study is to evaluate whether coadministration of ezetimibe 10 mg/day with simvastatin 20 mg/day for 12 weeks will result in greater reduction of LDL-C, total cholesterol (TC), triglycerides (TG), non HDL-C, and apolipoprotein B (ApoB), and greater increase in HDL-C, compared with simvastatin 20 mg/day as monotherapy for 12 weeks in African-American subjects with primary hypercholesterolemia. This study is being performed to better define the efficacy of ezetimibe coadministered with simvastatin in this population.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2004

Intervention(s) in this Clinical Trial

• Drug: Ezetimibe + Simvastatin
  • oral tablets; ezetimibe 10 mg and simvastatin 20 mg once daily for 12 weeks
• Drug: Simvastatin
  • oral tablet; simvastatin 20 mg once daily for 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Ezetimibe + Simvastatin
• Active Comparator: Simvastatin

Primary Measures

• Percent change in LDL-C from baseline to endpoint.
  • Time Frame: Week 12
    Safety Issue?: No

Secondary Measures

• Percent change from baseline to endpoint in TC, TG, HDL-C, non-HDL-C, and ApoB.
  • Time Frame: Week 12
    Safety Issue?: No

Inclusion Criteria:

• Adult African-American or Black subjects with diagnosis of primary hypercholesterolemia with plasma LDL-C >=145 mg/dL and <=250 mg/dL, and plasma TG
• <=350 mg/dL
• Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable HRT or raloxifene regimen for at least 6 weeks and throughout the study
• Female subjects of non-childbearing potential
• Willingness to give written consent, participate and complete all study-related procedures, and ability to follow a stable NCEP Step I (or stricter) diet regimen and keep a diet diary when required.
• Clinical laboratory tests (CBC, blood chemistries, and urinalysis) within normal limits (except as noted below) or clinically acceptable.
• ALT (SGPT) and AST (SGOT) concentrations <=2 times the upper limit of normal (ULN) and creatine phosphokinase <=2 times the ULN.

Exclusion Criteria:

• Pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study
• Secondary forms of hyperlipidemia or underlying disease likely to limit life span to less than one year
• Known hypersensitivity or any contraindication to simvastatin or ezetimibe
• Use of investigational drugs within 30 days of study entry
• Concomitant illnesses: congestive heart failure NYHA Class III or IV; obstructive cardiomyopathy; uncontrolled cardiac arrhythmias; severe aortic stenosis; MI, CABG or angioplasty within 3 months of study; unstable or severe peripheral artery disease;
• unstable angina pectoris; study-limiting disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease;
• uncontrolled or newly diagnosed diabetes mellitus; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (clinically euthyroid subjects on stable replacement doses of thyroid hormone are eligible for enrollment);
• uncontrolled hypertension; known impairment of renal function (plasma creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram); hepatobiliary or hepatic disease (AST or ALT >2 times the upper limit of the reference range); HIV positive; known coagulopathy.

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 Sponsor: Schering-Plough

Information obtained from ClinicalTrials.gov on August 21, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00650663

Study ID Number: P03377

ClinicalTrials.gov Identifier: NCT00650663

Health Authority: United States: Food and Drug Administration