A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01370603
First received: June 8, 2011
Last updated: November 11, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to determine whether ezetimibe/atorvastatin 10 mg/40 mg combination tablet is equivalent to the coadministration of ezetimibe 10 mg and atorvastatin 40 mg in lowering low-density-lipoprotein-cholesterol (LDL-C) after 6 weeks of treatment.


Condition Intervention Phase
Hypercholesterolemia
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Ezetimibe/atorvastatin
Drug: Placebo to atorvastatin
Drug: Placebo to ezetimibe
Drug: Placebo to ezetimibe/atorvastatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Active-Controlled, Multicenter, Crossover Study to Evaluate the Efficacy of Ezetimibe/Atorvastatin 10 mg/40 mg Fixed-Dose Combination Tablet Compared to Co-Administration of Marketed Ezetimibe 10 mg and Atorvastatin 40 mg in Patients With Primary Hypercholesterolemia

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 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.


Secondary Outcome Measures:
  • Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Serum TC measured at baseline and after 6 week of treatment in each of the 2 treatment periods.

  • Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Serum HDL-C measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

  • Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Non-HDL-C calculated at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

  • Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Serum Apo B measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

  • Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
    Serum TG measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.


Enrollment: 328
Study Start Date: September 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ezetimibe and atorvastatin
Medication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including 10 mg ezetimibe, 40 mg atorvastatin, and placebo to ezetimibe/atorvastatin.
Drug: Atorvastatin
40 mg tablet administered orally once daily
Other Name: Lipitor®
Drug: Ezetimibe
10 mg tablet administered orally once daily
Other Name: Zetia®
Drug: Placebo to ezetimibe/atorvastatin
Administered orally once daily
Experimental: Ezetimibe/atorvastatin combination
Medication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including ezetimibe/atorvastatin 10 mg/40 mg, placebo to ezetimibe, and placebo to atorvastatin.
Drug: Ezetimibe/atorvastatin
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet administered orally once daily
Other Names:
  • Liptruzet®
  • MK-0653C
Drug: Placebo to atorvastatin
Administered orally once daily
Drug: Placebo to ezetimibe
Administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • At low, moderate, or moderately high cardiovascular risk (according to National Cholesterol Education Program adult treatment panel III [NCEP ATP III] guidelines) and either statin-naïve with LDL-C ≥130 mg/dL for low risk or ≥100 mg/dL for moderate or moderately high risk OR on an allowable statin with on-therapy LDL-C ≥100 mg/dL in acceptable range and can safely discontinue and switch to study medication.
  • Is willing to maintain a cholesterol-lowering diet throughout the study.
  • Female of reproductive potential agrees to remain abstinent or to use (or have their partner use) 2 acceptable methods of birth control throughout the study.
  • Female receiving non-cyclical hormone therapy, if maintained on a stable dose and regimen for at least 8 weeks prior to the study and if willing to continue the same regimen throughout the study.
  • Off-therapy LDL-C levels are: for low risk patients, ≥130 mg/dL and ≤300 mg/dL; for moderate risk patients, ≥100 mg/dL and ≤300 mg/dL; for moderately high risk patients, ≥100 mg/dL and ≤275 mg/dL.
  • Has liver transaminases ≤2 X upper limit of normal (ULN) with no active liver disease.
  • Has creatine kinase (CK) levels ≤3 X ULN.
  • Has triglyceride (TG) concentrations ≤400 mg/dL.

Exclusion criteria:

  • Hypersensitivity or intolerance to ezetimibe, atorvastatin, the ezetimibe/atorvastatin combination tablet, or any component of these medications, or a history of myopathy or rhabdomyolysis with ezetimibe or any statin.
  • Routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week).
  • Is pregnant or lactating.
  • Has been treated with any other investigational drug within 30 days of the study.
  • Is high risk (according to NCEP ATP III guidelines), including but not limited to one or more of the following: diabetes mellitus (Type I or II), myocardial infarction, coronary artery bypass surgery, angioplasty, stable or unstable angina.
  • Has any of the following medical conditions: congestive heart failure; uncontrolled cardiac arrhythmias or recent significant changes in an electrocardiogram (ECG); homozygous familial hypercholesterolemia or has undergone LDL apheresis; partial ileal bypass, gastric bypass, or other significant intestinal malabsorption; uncontrolled hypertension; kidney disease; disease known to influence serum lipids or lipoproteins; hematologic, digestive, or central nervous system disorder; known to be human immunodeficiency virus (HIV) positive; history of malignancy ≤5 years prior to the study, except for adequately treated basal cell or squamous cell skin cancer or in situ

cervical cancer; mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.

- Taking prohibited medications/foods including: systemic azole antifungals (e.g., fluconazole, ketoconazole), erythromycin or clarithromycin, and cyclosporine; ritonavir and saquinavir or lopinavir; >5 cups of grapefruit juice per day; combination therapies of ezetimibe + atorvastatin (10/80 mg) or ezetimibe + rosuvastatin (10/20 mg or 10/40 mg); non-statin lipid-lowering agents including fish oils containing >900 mg/day of eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA), red yeast extract, Cholestin™, bile acid sequestrants, other cholesterol-lowering agents, niacin (>200 mg/day), or fibrates; systemic corticosteroids; psyllium, other fiber-based laxatives, phytosterol margarines, and/or over the counter (OTC) therapies known to affect serum lipid levels; orlistat or other anti-obesity medications and not maintained on a stable dose; any cyclical hormones; warfarin treatment without a stable dose or a stable International Normalized Ratio (INR).

  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01370603     History of Changes
Other Study ID Numbers: 0653C-190
Study First Received: June 8, 2011
Results First Received: May 21, 2013
Last Updated: November 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014