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)
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: Atorvastatin; Ezetimibe; Ezetimibe/atorvastatin; Placebo to atorvastatin; Placebo to ezetimibe; Placebo to ezetimibe/atorvastatin
Intervention description: 40 mg tablet administered orally once daily; 10 mg tablet administered orally once daily; Ezetimibe/atorvastatin 10 mg/40 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: 328.0
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/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.
    

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.

          -  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).