Ezetimibe/Simvastatin (10 mg/40 mg) vs. the Doubling of Atorvastatin in High Risk Participants (MK-0653A-134 AM1)(COMPLETED)

Study Overview
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Brief Summary
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Participants currently taking atorvastatin 20 mg will be switched to either atorvastatin 40 mg or ezetimibe/simvastatin 10 mg/40 mg (10/40). After 6 weeks of treatment, the percent reduction in low-density lipoprotein cholesterol (LDL-C) will be assessed and compared between the two treatment groups.

Official Title
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A Randomized, Double-Blind, Active-Controlled Study of Patients With Primary Hypercholesterolemia and High Cardiovascular Risk and Not Adequately Controlled With Atorvastatin: A Comparison of Switching to a Combination Tablet Ezetimibe/Simvastatin Versus Doubling the Baseline Dose of Atorvastatin

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: ezetimibe/simvastatin 10/40
* Drug: atorvastatin 40 mg
* Drug: atorvastatin 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are either statin naive or on approved lipid lowering therapy for 6 weeks prior to study initiation Participant meets Adult Treatment Panel (ATP) III High Risk criteria Exclusion Criteria: Females who are pregnant or breastfeeding Participant consumes more than 14 alcoholic beverages per week Participant has been treated with an investigational drug within the last 30 days Participant has congestive heart failure (New York Heart Association [NYHA] Type III or IV) Participant has had gastric bypass Participant is newly diagnosed with type 1 or 2 diabetes Participant is Human Immunodeficiency Virus (HIV) positive Participant has a history of drug or alcohol abuse within the last 5 years

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: ezetimibe/simvastatin 10/40<br>Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, ezetimibe/simvastatin 10/40 was administered once daily in tablet form during the 6-week double-blind treatment period | Drug: ezetimibe/simvastatin 10/40<br>* ezetimibe/simvastatin 10/40 tablet once daily for 6 weeks.<br>* Other names: Vytorin;Drug: atorvastatin 20 mg<br>* All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization<br>* Other names: Lipitor;|
| Active Comparator: atorvastatin 40 mg<br>Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, 40 mg atorvastatin was administered once daily in tablet form during the 6-week double-blind treatment period | Drug: atorvastatin 40 mg<br>* atorvastatin 40 mg tablet once daily for 6 weeks<br>* Other names: Lipitor;Drug: atorvastatin 20 mg<br>* All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Low Density Lipoprotein (LDL)-C |  | Baseline (Treatment Day 1), Treatment Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reaching LDL-C Target Goals of <70 mg/dL | Target LDL-C level of < 70 mg/dL (1.81 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population. | Treatment Week 6 | 
| Number of Participants Reaching LDL-C Target Goal <77 mg/dL | Target LDL-C level of < 77 mg/dL (2.00 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population. | Treatment Week 6 | 
| Number of Participants Reaching LDL-C Target Goal <100 mg/dL | Target LDL-C level of < 100 mg/dL (2.59 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population. | Treatment Week 6 | 
| Percent Change From Baseline in Total Cholesterol |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Triglycerides |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Non-HDL Cholesterol |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Apolipoprotein B |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Apolipoprotein A-1 |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in Apolipoprotein B/A-1 Ratio |  | Baseline (Treatment Day 1), Treatment Week 6 | 
| Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP) |  | Baseline (Treatment Day 1), Treatment Week 6 |