Ezetimibe Plus Simvastatin Versus Simvastatin in Patients With Hypercholesterolemia and Coronary Risk Factors (P03405)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Ezetimibe 10 mg or Placebo Co-administered With Existing Simvastatin 10mg or 20mg in Attaining Low-Density Lipoprotein Cholesterol Target Levels in Patients With Hypercholesterolemia and Coronary Heart Disease and/or Type II Diabetes

The study was designed to assess whether 6 weeks of co-administration of ezetimibe and simvastatin is more effective than simvastatin monotherapy in allowing patients in the CHD risk strata of the NCEP III guidelines to achieve their LDL-C target goal of <=3.0 mmol/L. As this study was to be conducted in Canada, the target LDL-C goal for patients with CHD, or type II diabetic patients >30 years old with no CHD, was <2.5 mmol/L.

Study Overview

• Status: Terminated
• Conditions: Atherosclerosis; Hypercholesterolemia
• Intervention / Treatment: Drug: Ezetimibe; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 82
• 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:

• >=18 years of age and treated with simvastatin 10 mg or 20 mg for at least 6 weeks and LDL-C levels of > 2.5 mmol/L to <=4.20 mmol/L (97 mg/dL to 160 mg/dL) at Visit 1.
• history of coronary heart disease (type II diabetic patients > 30 years old with no CHD)
• triglycerides <= 4.00 mmol/L drawn, and liver transaminases (ALT, AST) <=50% above the upper limit of normal at Visit 2, with no active liver disease, and/or creatine kinase (CK) <=50% above the upper limit of normal

Exclusion Criteria:

• subjects with Body Mass Index >=35 kg/sqm at Visit 1
• alcohol consumption > 14 drinks per week
• pregnant or lactating
• treated with any other investigational drug within 30 days prior Visit 1
• previously treated with ezetimibe or participated in a clinical study with ezetimibe
• any condition or situation which, in the opinion of the investigator, might pose a risk to the patient or interfere with participation in the study

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 tablet; ezetimibe placebo once daily for 6 weeks (added to ongoing simvastatin 10 or 20 mg once daily)
Experimental: Ezetimibe	Drug: Ezetimibe; oral tablet; ezetimibe 10 mg once daily for 6 weeks (added to ongoing simvastatin 10 or 20 mg once daily); Other Names: SCH 58235; Zetia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients reaching LDL-C goal of < 2.5 mmol/L (97 mg/dL) at endpoint.	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline to endpoint in LDL-C.	6 weeks
Percent change from baseline to endpoint in total cholesterol (TC) triglycerides, HDL-C, non-HDL-C, LDL-C/HDL-C ratio, TC/HDL-C ratio, and apolipoprotein B.	6 weeks
Safety/tolerability: adverse events, laboratory test results, vital signs.	Throughout study

Collaborators and Investigators

• Sponsor: Organon and Co
• Collaborators: Merck Frosst Canada Ltd.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: March 31, 2008
• First Submitted That Met QC Criteria: April 1, 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; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: P03405