A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1)
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: Atorvastatin; Ezetimibe; Ezetimibe/atorvastatin; Placebo to atorvastatin; Placebo to ezetimibe; Placebo to ezetimibe/atorvastatin
Intervention description: 20 mg tablet administered orally once daily; 10 mg tablet administered orally once daily; Ezetimibe/atorvastatin 10 mg/20 mg combination tablet administered orally once daily; Administered orally once daily; Administered orally once daily; Administered orally once daily
Intervention MeSH terms: Atorvastatin; Ezetimibe
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 406.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether ezetimibe/atorvastatin 10 mg/20 mg
      combination tablet is equivalent to the coadministration of ezetimibe 10 mg and atorvastatin
      20 mg in lowering low-density-lipoprotein-cholesterol (LDL-C) after 6 weeks of treatment.
    

Eligibility 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.

          -  Has any condition or situation that might pose a risk to the participant or interfere
             with participation in 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 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 systems 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 + simvastatin (10/80 mg), ezetimibe + atorvastatin
             (10/40 mg or 10/80 mg), ezetimibe + rosuvastatin (10/10 mg, 10/20 mg, or 10/40 mg),
             ezetimibe + pitavastatin (10/4 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).