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

Study Overview
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Brief Summary
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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
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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

Conditions
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Hypercholesterolemia, Atherosclerosis

Intervention / Treatment
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* Drug: Ezetimibe + Simvastatin
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ezetimibe + Simvastatin<br> | Drug: Ezetimibe + Simvastatin<br>* oral tablets; ezetimibe 10 mg and simvastatin 20 mg once daily for 12 weeks<br>* Other names: SCH 58235;|
| Active Comparator: Simvastatin<br> | Drug: Simvastatin<br>* oral tablet; simvastatin 20 mg once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in LDL-C from baseline to endpoint. |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline to endpoint in TC, TG, HDL-C, non-HDL-C, and ApoB. |  | Week 12 |