Phase 3 N=808 Randomized Double-blind Treatment

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

Cardiovascular Disorder · Diabetes Mellitus

Bottom Line

View on ClinicalTrials.gov: NCT00862251 ↗

Enrolled (actual)

808

Serious AEs

0.6%

Results posted

Mar 2012

Primary outcome: Primary: 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). — -23.13; -8.37 Percent change — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: ezetimibe (+) simvastatin (Drug); simvastatin 40 mg or atorvastatin 20 mg (Drug); Rosuvastatin (Drug); atorvastatin 10 mg or simvastatin 20 mg (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Organon and Co
Primary completion: Mar 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY 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).	-23.13; -8.37	<0.001 sig
SECONDARY 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	-21.59; -7.98	<0.001 sig
SECONDARY 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	-24.58; -8.85	<0.001 sig
SECONDARY Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin	-23.13; -19.32	0.060
SECONDARY Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	171; 43; 134	<0.001 sig
SECONDARY 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)	84; 19	<0.001 sig
SECONDARY 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)	87; 24	<0.001 sig
SECONDARY Percent Change From Baseline in Total Cholesterol (TC)	-13.21; -4.88; -10.58	<0.001 sig
SECONDARY Percent Change From Baseline in Triglycerides	-5.51; -2.63; -3.35	0.316
SECONDARY Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	1.47; 1.00; 1.99	0.756
SECONDARY Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	-18.39; -6.77; -15.14	<0.001 sig
SECONDARY Percent Change From Baseline in LDL-C/HDL-C Ratio	-21.55; -7.39; -18.99	<0.001 sig
SECONDARY Percent Change From Baseline in TC/HDL-C Ratio	-12.52; -4.36; -10.70	<0.001 sig
SECONDARY Percent Change From Baseline in Non-HDL-C/HDL-C Ratio	-16.77; -5.32; -14.64	<0.001 sig
SECONDARY Percent Change From Baseline in Apolipoprotein B (Apo B)	-14.98; -6.97; -12.03	<0.001 sig
SECONDARY Percent Change From Baseline Apolipoprotein A-I (Apo A-I)	0.64; -0.93; 0.86	0.218
SECONDARY Percent Change From Baseline in Apo B/Apo A-I Ratio	-13.67; -4.75; -11.14	<0.001 sig
SECONDARY Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP)	-4.42; -1.64; -9.11	0.749

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.

Eligibility Criteria

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

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Data sourced from ClinicalTrials.gov (NCT00862251). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.