Ezetimibe/Simvastatin (MK-0653A) Versus Rosuvastatin Versus Doubling Statin Dose in Participants With Cardiovascular Disease and Diabetes Mellitus (MK-0653A-133)(COMPLETED)

Phase 3

Completed

• Conditions: Cardiovascular Disorder; Diabetes Mellitus
• Interventions: Drug: ezetimibe (+) simvastatin; Drug: simvastatin 40 mg or atorvastatin 20 mg; Drug: Rosuvastatin; Drug: atorvastatin 10 mg or simvastatin 20 mg

• Registration Number: NCT00862251
• Lead Sponsor: Organon and Co

Brief Summary

The purpose of this study is to determine the efficacy of switching to a combination tablet ezetimibe/simvastatin (10mg/20mg) versus rosuvastatin (10 mg) versus doubling the statin dose in those patients who have cardiovascular disease and diabetes mellitus not adequately controlled on simvastatin 20 mg or atorvastatin 10 mg.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-03-12
• Study First Submitted QC: 2009-03-13
• Study First Posted: 2009-03-16
• Study Start: 2009-04
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Results First Submitted: 2012-02-23
• Results First Submitted QC: 2012-02-23
• Results First Posted: 2012-03-16
• Status Verified: 2022-02
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 808

Inclusion Criteria

• Patient has not taken common statins or ezetimibe within 6 weeks of study screening or patient is currently taking a daily dose of the following statins for 6 weeks prior to study screening: simvastatin, atorvastatin, pravastatin, fluvastatin, ezetimibe, lovastatin, or ezetimibe + fluvastatin
• Patient is willing to go on a cholesterol and glucose lowering diet for the duration of the study
• Patient is willing to remain abstinent or use birth control for the duration of the study
• Patient has Diabetes Mellitus with cardiovascular disease

Exclusion Criteria

• Patient has sensitivity to certain common statin drugs
• Patient is Asian and would not be able to start taking the higher doses of rosuvastatin necessary for the study design
• Patient consumes more than 2 alcoholic drinks per day
• Patient is pregnant or breast-feeding
• Patient has been treated with other investigational drugs within 30 days of first visit
• Patient is currently on prohibited doses of the following statin drugs: rosuvastatin, simvastatin, atorvastatin, and pravastatin
• Patient has congestive heart failure
• Patient has uncontrolled high blood pressure
• Patient has kidney disease
• Patient has uncontrolled endocrine or metabolic disease which are known to possibly increase blood lipoproteins
• Patient has diabetes mellitus that is not well controlled
• Patient is human immunodeficiency virus (HIV) positive
• Patient is currently taking medications that inhibit Cytochrome P450 3A4 (CYP3A4)
• Patient is currently taking therapies that would increase the risk of muscle weakness
• Patient has been taking certain over- the-counter lipid-lowering agents within 6 weeks prior to visit 1
• Patient is currently taking psyllium or other fiber-based laxatives

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Doubling statin dose	atorvastatin 10 mg or simvastatin 20 mg	-
Ezetimibe/simvastatin	atorvastatin 10 mg or simvastatin 20 mg	-
Ezetimibe/simvastatin	ezetimibe (+) simvastatin	-
Doubling statin dose	simvastatin 40 mg or atorvastatin 20 mg	-
Rosuvastatin	atorvastatin 10 mg or simvastatin 20 mg	-
Rosuvastatin	Rosuvastatin	-

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin).	Baseline and Week 6

Secondary Outcome Measures

Name	Time	Method
In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin	Baseline and Week 6
Percent Change From Baseline in TC/HDL-C Ratio	Baseline and Week 6
Percent Change From Baseline Apolipoprotein A-I (Apo A-I)	Baseline and Week 6
In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	Week 6
Percent Change From Baseline in Total Cholesterol (TC)	Baseline and Week 6
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	Baseline and Week 6
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Baseline and Week 6
In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin	Baseline and Week 6
Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin	Baseline and Week 6
Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	Week 6
Percent Change From Baseline in Triglycerides	Baseline and Week 6
Percent Change From Baseline in LDL-C/HDL-C Ratio	Baseline and Week 6
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio	Baseline and Week 6
Percent Change From Baseline in Apolipoprotein B (Apo B)	Baseline and Week 6
Percent Change From Baseline in Apo B/Apo A-I Ratio	Baseline and Week 6
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP)	Baseline and Week 6
In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	Week 6