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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: ezetimibe/simvastatin 10/40; Drug: atorvastatin 20 mg; Drug: atorvastatin 40 mg

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ezetimibe/simvastatin 10/40; 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; ezetimibe/simvastatin 10/40 tablet once daily for 6 weeks.; Other Names: Vytorin; Drug: atorvastatin 20 mg; All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization; Other Names: Lipitor
Active Comparator: atorvastatin 40 mg; 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 20 mg; All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization; Other Names: Lipitor; Drug: atorvastatin 40 mg; atorvastatin 40 mg tablet once daily for 6 weeks; Other Names: Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, Milardo C, Triscari J. Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study. Lipids Health Dis. 2012 Jan 31;11:18. doi: 10.1186/1476-511X-11-18.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 29, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Actual): February 14, 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: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
• Other Study ID Numbers: 0653A-134; 2008_576

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php