Overview

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)

Status:
Completed
Trial end date:
2012-05-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Merck Sharp & Dohme Corp.
Treatments:
Atorvastatin
Atorvastatin Calcium
Ezetimibe
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).