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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hypercholesterolemia, Atherosclerosis

Intervention / Treatment
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* Drug: Ezetimibe
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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<br> | Drug: Ezetimibe<br>* oral tablet; ezetimibe 10 mg once daily for 6 weeks (added to ongoing simvastatin 10 or 20 mg once daily)<br>* Other names: Zetia;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* oral tablet; ezetimibe placebo once daily for 6 weeks (added to ongoing simvastatin 10 or 20 mg once daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |