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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00862251
First received: March 12, 2009
Last updated: March 26, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Cardiovascular Disorder
Diabetes Mellitus
Drug: ezetimibe (+) simvastatin
Drug: simvastatin 40 mg or atorvastatin 20 mg
Drug: Rosuvastatin
Drug: atorvastatin 10 mg or simvastatin 20 mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Active-Controlled Study of Patients With Cardiovascular Disease and Diabetes Mellitus Not Adequately Controlled With Simvastatin or Atorvastatin: Comparison of Switching to Combination Tablet Ezetimibe/Simvastatin Versus Switching to Rosuvastatin or Doubling the Statin Dose

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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). [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol (TC) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in LDL-C/HDL-C Ratio [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in TC/HDL-C Ratio [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-HDL-C/HDL-C Ratio [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline Apolipoprotein A-I (Apo A-I) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apo B/Apo A-I Ratio [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]

Enrollment: 808
Study Start Date: April 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ezetimibe/simvastatin Drug: ezetimibe (+) simvastatin
ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks.
Other Name: Vytorin
Drug: atorvastatin 10 mg or simvastatin 20 mg
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Other Name: Lipitor, Zocor
Active Comparator: Doubling statin dose Drug: simvastatin 40 mg or atorvastatin 20 mg
simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.
Other Name: Lipitor, Zocor
Drug: atorvastatin 10 mg or simvastatin 20 mg
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Other Name: Lipitor, Zocor
Active Comparator: Rosuvastatin Drug: Rosuvastatin
rosuvastatin 10 mg tablets, taken once daily for six weeks.
Other Name: Crestor
Drug: atorvastatin 10 mg or simvastatin 20 mg
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Other Name: Lipitor, Zocor

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00862251

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00862251     History of Changes
Other Study ID Numbers: MK-0653A-133, 2009_559
Study First Received: March 12, 2009
Results First Received: February 23, 2012
Last Updated: March 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
cardiovascular disorder

Additional relevant MeSH terms:
Cardiovascular Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Atorvastatin
Simvastatin
Rosuvastatin
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014