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

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 Overview

• Status: Completed
• Conditions: Atherosclerosis; Hypercholesterolemia
• Intervention / Treatment: Drug: Ezetimibe + Simvastatin; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Organon and Co
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Rodney RA, Sugimoto D, Wagman B, Zieve F, Kerzner B, Strony J, Yang B, Suresh R, Veltri E. Efficacy and safety of coadministration of ezetimibe and simvastatin in African-American patients with primary hypercholesterolemia. J Natl Med Assoc. 2006 May;98(5):772-8.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2003
• Primary Completion (Actual): September 1, 2004
• Study Completion (Actual): September 1, 2004

Study Registration Dates

• First Submitted: March 31, 2008
• First Submitted That Met QC Criteria: March 31, 2008
• First Posted (Estimate): April 2, 2008

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Ezetimibe
• Other Study ID Numbers: P03377

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis