Ezetimibe/Simvastatin in Patients With Metabolic Syndrome (0653A-107)(COMPLETED)

A Multicenter, Randomized, Double-Blind, Parallel Arm, 6-Week Study to Evaluate the Efficacy and Safety of Ezetimibe/Simvastatin Versus Atorvastatin in Patients With Metabolic Syndrome and Hypercholesterolemia at High Risk for Coronary Heart Disease

A 6-week clinical trial in patients with metabolic syndrome and hypercholesterolemia at high risk for coronary heart disease to study the effects of ezetimibe/simvastatin and atorvastatin on lipids.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Hypercholesterolemia
• Intervention / Treatment: Drug: ezetimibe (+) simvastatin; Drug: Comparator: atorvastatin calcium; Drug: Comparator: Placebo (unspecified)

• Study Type: Interventional
• Enrollment (Actual): 1143
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients 18 to 79 years of age with metabolic syndrome and hypercholesterolemia at high risk for coronary heart disease (CHD) with LDL-C above 70 mg/dL or 100 mg/dL depending on their CHD risk category

Exclusion Criteria:

• A condition which, in the opinion of the investigator, pose a risk to the patient or interfere with participating in the study
• Patient is likely to be greater than 20% noncompliant in taking study medications
• Patients with chronic medical conditions
• Patients with unstable doses of medications
• Pregnant or lactating women, women intending to become pregnant
• Patient is currently receiving prescription therapy with statins or other lipid-altering medications
• Patient with Type 1 or Type 2 diabetes mellitus that is poorly controlled, newly diagnosed, or is taking new or recently adjusted antidiabetic pharmacotherapy (with the exception of +/- 10 units of insulin)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; Arm 1: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A; Vytorin®; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ®; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 2; Arm 2: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A; Vytorin®; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ®; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 3; Arm 3: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A; Vytorin®; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ®; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 4; Arm 4: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A; Vytorin®; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ®; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 5; Arm 5: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A; Vytorin®; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ®; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 6	Baseline and 6 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Total Cholesterol(mg/dL) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Triglyceride (TG) (mg/dL) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Non- High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Apolipoprotein- B (Apo-B) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Apolipoprotein-A1 (Apo-A1) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Total-Cholesterol: High Density Lipoprotein-Cholesterol (Total-C:HDL- C) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Low Density Lipoprotein Cholesterol: High Density Lipoprotein Cholesterol (LDL-C: HDL-C) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Apolipoprotein-B: Apolipoprotein-A1 (Apo-B:Apo-A1) at Week 6	Baseline and 6 weeks
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol: High Density Lipoprotein Cholesterol (Non-HDL-C:HDL-C) at Week 6	Baseline and 6 Weeks
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 6 in Patients With Atherosclerotic Vascular Disease (AVD)	Baseline and 6 Weeks
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 6 in Patients Without Atherosclerotic Vascular Disease (AVD)	Baseline and 6 Weeks
Percent Change From Baseline in High-Sensitivity C-reactive (Hs-CRP) (mg/dL) at Week 6	Baseline and 6 Weeks

Collaborators and Investigators

• Sponsor: Organon and Co
• Investigators: Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Rosen JB, Ballantyne CM, Hsueh WA, Lin J, Shah AK, Lowe RS, Tershakovec AM. Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk. Lipids Health Dis. 2015 Sep 4;14:103. doi: 10.1186/s12944-015-0075-5.
• Robinson JG, Ballantyne CM, Hsueh W, Rosen J, Lin J, Shah A, Lowe RS, Hanson ME, Tershakovec AM. Achievement of specified low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol apolipoprotein B, and high-sensitivity C-reactive protein levels with ezetimibe/simvastatin or atorvastatin in metabolic syndrome patients with and without atherosclerotic vascular disease (from the VYMET study). J Clin Lipidol. 2011 Nov-Dec;5(6):474-82. doi: 10.1016/j.jacl.2011.06.004. Epub 2011 Jun 15.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: December 8, 2006
• First Submitted That Met QC Criteria: December 8, 2006
• First Posted (Estimated): December 11, 2006

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Syndrome; Metabolic Syndrome; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Calcium-Regulating Hormones and Agents; Atorvastatin; Calcium; Simvastatin; Ezetimibe
• Other Study ID Numbers: 0653A-107; 2006_527

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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