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.
Minimum age: 18 Years.
Maximum age: 79 Years.
Gender(s): Both.
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).