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)

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01370590
• Other study ID #: 0653C-185
• Status: Completed
• Phase: Phase 3
• Start date: September 2011
• Est. completion date: April 2012

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Atorvastatin
20 mg tablet administered orally once daily
• Ezetimibe
10 mg tablet administered orally once daily
• Ezetimibe/atorvastatin
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet administered orally once daily
• Placebo to atorvastatin
Administered orally once daily
• Placebo to ezetimibe
Administered orally once daily
• Placebo to ezetimibe/atorvastatin
Administered orally once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & 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): — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment	Serum TC measured at baseline and after 6 week of treatment in each of the 2 treatment periods.	Baseline and Week 6
Secondary	Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment	Serum HDL-C calculated at baseline and after 6 weeks of treatment in each of the 2 treatment periods.	Baseline and Week 6
Secondary	Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment	Non-HDL-C measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.	Baseline and Week 6
Secondary	Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment	Serum Apo B measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.	Baseline and Week 6
Secondary	Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment	Serum TG measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.	Baseline and Week 6