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)

NCT ID: NCT01370603

Last Updated: 2022-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 328 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-05-31

Brief 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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ezetimibe and atorvastatin

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.

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

40 mg tablet administered orally once daily

Ezetimibe

Intervention Type: DRUG

10 mg tablet administered orally once daily

Placebo to ezetimibe/atorvastatin

Intervention Type: DRUG

Administered orally once daily

Ezetimibe/atorvastatin combination

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.

Group Type: EXPERIMENTAL

Ezetimibe/atorvastatin

Intervention Type: DRUG

Ezetimibe/atorvastatin 10 mg/40 mg combination tablet administered orally once daily

Placebo to atorvastatin

Intervention Type: DRUG

Administered orally once daily

Placebo to ezetimibe

Intervention Type: DRUG

Administered orally once daily

Interventions

Atorvastatin

40 mg tablet administered orally once daily

Intervention Type: DRUG

Ezetimibe

10 mg tablet administered orally once daily

Intervention Type: DRUG

Ezetimibe/atorvastatin

Ezetimibe/atorvastatin 10 mg/40 mg combination tablet administered orally once daily

Intervention Type: DRUG

Placebo to atorvastatin

Administered orally once daily

Intervention Type: DRUG

Placebo to ezetimibe

Administered orally once daily

Intervention Type: DRUG

Placebo to ezetimibe/atorvastatin

Administered orally once daily

Intervention Type: DRUG

Other Intervention Names

Lipitor®; Zetia®; Liptruzet®; MK-0653C

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Organon and Co

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Bays HE, Chen E, Tomassini JE, McPeters G, Polis AB, Triscari J. Fixed-dose combination ezetimibe+atorvastatin lowers LDL-C equivalent to co-administered components in randomized trials: use of a dose-response model. Fundam Clin Pharmacol. 2015 Apr;29(2):209-18. doi: 10.1111/fcp.12096. Epub 2015 Feb 27.

Reference Type: RESULT

PMID: 25431239 (View on PubMed)

Other Identifiers

0653C-190

Identifier Type: -

Identifier Source: org_study_id