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)

• ClinicalTrials.gov Identifier: NCT01370590
• Recruitment Status: Completed
• First Posted: June 10, 2011
• Results First Posted: August 5, 2013
• Last Update Posted: February 9, 2022
• Sponsor: Organon and Co
• Information provided by (Responsible Party): Organon and Co

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: Atorvastatin; Drug: Ezetimibe; Drug: Ezetimibe/atorvastatin; Drug: Placebo to atorvastatin; Drug: Placebo to ezetimibe; Drug: Placebo to ezetimibe/atorvastatin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 406 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Active-Controlled, Multicenter, Crossover Study to Evaluate the Efficacy and Safety of Ezetimibe/Atorvastatin 10 mg/20 mg Fixed-Dose Combination Tablet Compared to Co-administration of Marketed Ezetimibe 10 mg and Atorvastatin 20 mg in Patients With Primary Hypercholesterolemia
• Study Start Date: September 2011
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Ezetimibe and atorvastatin; Medication will be administered in a double dummy fashion as 3 tablets orally on a daily basis, including 10 mg ezetimibe, 20 mg atorvastatin, and placebo to ezetimibe/atorvastatin.	Drug: Atorvastatin; 20 mg tablet administered orally once daily; Other Name: Lipitor®; Drug: Ezetimibe; 10 mg tablet administered orally once daily; Other Name: Zetia®; Drug: Placebo to ezetimibe/atorvastatin; Administered orally once daily
Experimental: 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/20 mg, placebo to ezetimibe, and placebo to atorvastatin.	Drug: Ezetimibe/atorvastatin; Ezetimibe/atorvastatin 10 mg/20 mg combination tablet administered orally once daily; Other Names: Liptruzet®; MK-0653C; Drug: Placebo to atorvastatin; Administered orally once daily; Drug: Placebo to ezetimibe; Administered orally once daily

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ]
   Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

Secondary Outcome Measures :

1. Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ]
   Serum TC measured at baseline and after 6 week of treatment in each of the 2 treatment periods.
2. Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ]
   Serum HDL-C calculated at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
3. Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ]
   Non-HDL-C measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
4. Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ]
   Serum Apo B measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
5. Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment [ Time Frame: Baseline and Week 6 ]
   Serum TG measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

No Contacts or Locations Provided

More Information

Publications of Results:

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.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01370590
• Other Study ID Numbers: 0653C-185
• First Posted: June 10, 2011
• Results First Posted: August 5, 2013
• Last Update Posted: February 9, 2022
• Last Verified: February 2022

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Atorvastatin; Ezetimibe; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors