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)

NCT01370603 | Completed Phase 3 Results

• 1 other identifier: 0653C-190
• Study Type: interventional
• Target: 328
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment

  Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.

  Baseline and Week 6

Secondary Outcomes (5)

• Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment

  Baseline and Week 6

• Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment

  Baseline and Week 6

• Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment

  Baseline and Week 6

• Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment

  Baseline and Week 6

• Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment

  Baseline and Week 6

Study Arms (2)

Ezetimibe and atorvastatin

ACTIVE COMPARATOR

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.

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

Ezetimibe/atorvastatin combination

EXPERIMENTAL

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.

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

Interventions

Atorvastatin DRUG

40 mg tablet administered orally once daily

Also known as: Lipitor®

Ezetimibe and atorvastatin

Ezetimibe DRUG

10 mg tablet administered orally once daily

Also known as: Zetia®

Ezetimibe and atorvastatin

Ezetimibe/atorvastatin DRUG

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

Also known as: Liptruzet®, MK-0653C

Ezetimibe/atorvastatin combination

Placebo to atorvastatin DRUG

Administered orally once daily

Ezetimibe/atorvastatin combination

Placebo to ezetimibe DRUG

Administered orally once daily

Ezetimibe/atorvastatin combination

Placebo to ezetimibe/atorvastatin DRUG

Administered orally once daily

Ezetimibe and atorvastatin

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• 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.

  PMID: 25431239 RESULT

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Atorvastatin; Ezetimibe; liptruzet

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Azetidines; Azetines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 10, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: February 9, 2022
• Results First Posted: July 10, 2013

Record last verified: 2022-02