Ezetimibe Plus Simvastatin Versus Simvastatin Alone in African-American Subjects With Primary Hypercholesterolemia (P03377)

Condition(s) targeted: Hypercholesterolemia; Atherosclerosis

Intervention: Ezetimibe + Simvastatin (Drug); Simvastatin (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Schering-Plough

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.

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

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

Primary outcome: Percent change in LDL-C from baseline to endpoint.

Secondary outcome: Percent change from baseline to endpoint in TC, TG, HDL-C, non-HDL-C, and ApoB.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Starting date: October 2003
Ending date: September 2004
Last updated: March 31, 2008