Comparison of Co-administration of Ezetimibe Plus Simvastatin Versus Simvastatin Alone in Primary Hypercholesterolemia (P03476)

A Multicenter, Randomized, Parallel Groups, Placebo-Controlled Study Comparing The Efficacy, Safety, And Tolerability Of The Daily Co-administration Of Ezetimibe 10 Mg Or Ezetimibe Placebo To Ongoing Treatment With Simvastatin 20 Mg In Subjects With Primary Hypercholesterolemia And Coronary Heart Disease

This study will assess whether the daily co-administration of ezetimibe 10 mg with ongoing treatment of simvastatin 20 mg will be more effective than treatment with simvastatin 20 mg alone in further reducing LDL-C concentrations.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Hypercholesterolemia; Coronary Heart Disease
• Intervention / Treatment: Drug: Ezetimibe; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
• Subjects must be >= 18 years and <= 75 years of age.
• Subjects must have an LDL-C concentration >= 2.6 mmol/L (100 mg/dL) to <= 4.1 mmol/L (160 mg/dL) using the Friedewald calculation available at the time of randomization Visit 3 (Baseline Visit).
• Subjects must have triglyceride concentrations of < 3.99 mmol/L (350 mg/dL) at Visit 3 (Baseline Visit).
• Subjects must have documented coronary heart disease (CHD). For the purposes of this study, CHD will include one or more of the following features: documented stable angina (with evidence of ischemia on exercise testing); history of myocardial infarction; history of percutaneous coronary intervention (primarily PTCA with or without stent placement); symptomatic peripheral vascular disease (claudication); documented history of atherothrombotic cerebrovascular disease; and/or documented history of unstable angina or non-Q wave myocardial infarction.
• Subject must be currently taking simvastatin 20 mg daily and by history has taken 80% of daily evening doses for the preceding 6 weeks prior to Visit 3 (Baseline Visit).
• Subjects must have liver transaminases (ALT, AST) < 50% above the upper limit of normal, with no active liver disease, and CK < 50% above the upper limit of normal at Visit 3 (Baseline Visit).
• Clinical laboratory tests (CBC, blood chemistries, urinalysis) must be within normal limits or clinically acceptable to the investigator at Visit 3 (Baseline Visit).
• Subjects must have maintained a cholesterol lowering diet program for at least 4 weeks prior to the study and be willing to continue the same diet program during the study.
• Subjects must report a stable weight history for at least 4 weeks prior to entry into study at Visit 3 (Baseline Visit).
• Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study.
• Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation).
• Subjects must be free of any clinically significant diseases other than hyperlipidemia or coronary heart disease that would interfere with study evaluations.
• Subjects must understand and be able to adhere to the dosing and visit schedules, and must agree to remain on their cholesterol-lowering diet and their exercise regimen for the duration of the study.

Exclusion Criteria:

• Subjects whose body mass index (BMI) is >= 30 Kg/m^2 at Visit 3 (Baseline Visit).
• Subjects who consume > 14 alcoholic drinks per week. (A drink is: a can of beer, glass of wine, or single measure of spirits).
• Any condition or situation which, in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study.
• Women who are pregnant or nursing.
• Subjects who have not observed the designated washout periods for any of the prohibited medications

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
Placebo Comparator: Placebo	Drug: Placebo; oral tablets: placebo to match ezetimibe 10 mg once daily for 6 weeks (plus continued simvastatin)
Experimental: Ezetimibe	Drug: Ezetimibe; oral tablets: ezetimibe 10 mg once daily for 6 weeks (plus continued simvastatin); Other Names: SCH 58235

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in LDL-cholesterol with ezetimibe added to simvastatin versus continued simvastatin alone.	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects who achieve target LDL-C as defined by the ESC or NCEP guidelines with ezetimibe added to simvastatin versus continued simvastatin alone	6 weeks
Percent change from baseline in total cholesterol, HDL-C and triglycerides with ezetimibe added to simvastatin versus continued simvastatin alone.	6 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Zubaid M, Shakir DK, Bazargani N, Binbrek A, Gopal R, Al-Tamimi O, Bakir S. Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial. J Cardiovasc Med (Hagerstown). 2008 Jul;9(7):688-93. doi: 10.2459/JCM.0b013e3282f3a1b1.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2003
• Primary Completion (Actual): August 1, 2004
• Study Completion (Actual): August 1, 2004

Study Registration Dates

• First Submitted: March 31, 2008
• First Submitted That Met QC Criteria: April 1, 2008
• First Posted (Estimated): April 2, 2008

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• 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; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hypercholesterolemia; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: P03476

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis