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)

Organon

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: Placebo to ezetimibe/atorvastatin; Drug: Ezetimibe; Drug: Atorvastatin; Drug: Ezetimibe/atorvastatin; Drug: Placebo to ezetimibe; Drug: Placebo to atorvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01370603

0653C-190

Details and patient eligibility

About

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.

Enrollment: 328 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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328 participants in 2 patient groups

Ezetimibe and atorvastatin

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to ezetimibe/atorvastatin

Drug: Atorvastatin

Drug: Ezetimibe

Ezetimibe/atorvastatin combination

Experimental group

Description:

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.

Treatment:

Drug: Placebo to atorvastatin

Drug: Placebo to ezetimibe

Drug: Ezetimibe/atorvastatin