A Study of Ezetimibe Added On to Rosuvastatin Versus Up Titration of Rosuvastatin in Patients With Hypercholesterolemia (MK0653-139)

Study Overview
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Brief Summary
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A study to evaluate the low-density lipoprotein cholesterol (LDL-C) lowering efficacy of the addition of ezetimibe to rosuvastatin compared with doubling dose of rosuvastatin in participants treated with rosuvastatin alone and not at their National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal

Official Title
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A Multicenter, Randomized, Double-Blind, Titration Study to Evaluate the Efficacy and Safety of Ezetimibe Added On to Rosuvastatin Versus Up Titration of Rosuvastatin in Patients With Hypercholesterolemia at Risk for Coronary Heart Disease

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Comparator: rosuvastatin 5 mg + ezetimibe 10 mg
* Drug: Comparator: rosuvastatin 10 mg
* Drug: Comparator: rosuvastatin 10 mg + ezetimibe 10 mg
* Drug: Comparator: rosuvastatin 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is currently taking a stable dose of lipid lowering agent(s). (if applicable) or is statin naive Participant is currently taking a stable dose of lipid lowering agent(s). (if is at least moderate high risk for Coronary Heart Disease (CHD)) Participant is currently taking a stable dose of lipid lowering agent(s). (if is willing to maintain Therapeutic Lifestyle Changes (TLC) / American Diabetes Association(ADA) diet) Exclusion Criteria: Participant weighs less than 100 lbs (45 kg). Participant has hypersensitivity or intolerance to ezetimibe, or rosuvastatin or any components of these medications. If female, participant is pregnant or breastfeeding. Participant consumes more than 2 alcoholic beverages per day. Participant has been in a clinical trial within the last 30 days. Participant has heart problems such as CHF, unstable angina or heart attack. Participant has type 1 or 2 diabetes and has changed their medication in the last 2 months. Participant has liver disease. Participant is Human Immunodeficiency Virus (HIV) positive. Participant has a history of drug or alcohol abuse in the last year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin 5 mg + Ezetimibe 10 mg<br>Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 5 mg rosuvastatin for an additional 6 weeks. | Drug: Comparator: rosuvastatin 5 mg + ezetimibe 10 mg<br>* Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 5 mg rosuvastatin for an additional 6 weeks.<br>* Other names: Crestor, Zetia;|
| Active Comparator: Rosuvastatin 10 mg<br>Participants who received rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks. | Drug: Comparator: rosuvastatin 10 mg<br>* Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.<br>* Other names: Crestor;|
| Experimental: Rosuvastatin 10 mg + Ezetimibe 10 mg<br>Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 10 mg rosuvastatin for an additional 6 weeks. | Drug: Comparator: rosuvastatin 10 mg + ezetimibe 10 mg<br>* Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 10 mg rosuvastatin for an additional 6 weeks.<br>* Other names: Crestor, Zetia;|
| Active Comparator: Rosuvastatin 20 mg<br>Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks. | Drug: Comparator: rosuvastatin 20 mg<br>* Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in LDL-Cholesterol (mg/dL) After 6 Weeks of Treatment | The percent change from baseline in LDL-C (mg/dL) after 6 weeks of treatment in participants who were administered ezetimibe 10 mg to rosuvastatin (5 or 10 mg) in comparison with doubling the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks. | Baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in LDL-Cholesterol (mg/dL) After 6 Weeks of Treatment in Each Stratum | The percent change from baseline in LDL-C (mg/dL) after 6 weeks of treatment by stratum I and stratum II in participants who were administered with ezetimibe 10 mg to rosuvastatin (5 or 10 mg) in comparison with the doubling of the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks. | Baseline to 6 weeks | 
| Number of Participants Who Reached Their Target LDL-C Level | Participants were analyzed to evaluate the LDL-C (<100 mg/dL for moderately high risk patients and high risk patients without AVD and <70 mg/dL for high risk patients with AVD) lowering efficacy with the addition of ezetimibe 10 mg to (5 or 10 mg) compared with doubling the baseline rosuvastatin (10 or 20 mg), daily for 6 weeks of treatment. | 6 weeks of treatment | 
| Number of Participants in Each Stratum Who Reached Their Target LDL-C Level | Participants in stratum I were analyzed to evaluate the LDL-C lowering efficacy with the additional of ezetimibe 10 mg to rosuvastatin 5 mg daily for 6 weeks compared with doubling the baseline dose to rosuvastatin 10 mg daily for 6 weeks. Participants in stratum II were analyzed to evaluate the LDL-C lowering efficacy with the additional of ezetimibe 10 mg to rosuvastatin 10 mg daily for 6 weeks compared with doubling the baseline dose to rosuvastatin 20 mg daily for 6 weeks. | 6 weeks of treatment | 
| Number of Participants Who Reached the LDL-C Level of <70 mg/dl | Participants across all strata who reached the LDL-C Level of <70 mg/dl after the addition of ezetimibe 10 mg to rosuvastatin (5 or 10 mg) daily for 6 weeks compared with doubling the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks. | 6 weeks of treatment | 
| Number of Participants in Each Stratum Who Reached the LDL-C Level of <70 mg/dl | Participants in stratum I and in stratum II who reached the LDL-C Level of <70 mg/dl after the addition of ezetimibe to rosuvastatin (5 or 10 mg)daily for 6 weeks compared with doubling the baseline dose of rosuvastatin (10 or 20 mg). | 6 weeks of treatment | 
| Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels | Participants who were analyzed to assess the Total Cholesterol (TC), Triglycerides, High-Density Lipoprotein Cholesterol, Non High-Density Lipoprotein Cholesterol, LDL Cholesterol/HDL Cholesterol, Total Cholesterol/HDL Cholesterol, Non-HDL Cholesterol/HDL Cholesterol, Apolipoprotein B (Apo B), Apolipoprotein A-I (Apo A-I), Apolipoprotein B/Apo A-I, high-sensitivity C-reactive protein (hs-CRP)levels after 6 weeks of treatment. | Baseline to 6 weeks |