- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03867110
An Efficacy and Safety Study of Ezetimibe (MK-0653, SCH 58235) in Addition to Atorvastatin Compared to Placebo in Participants With Primary Hypercholesterolemia (MK-0653-013)
February 7, 2022 updated by: Organon and Co
A Phase 3, Double-Blind Efficacy and Safety Study of Ezetimibe (SCH 58235) 10 mg in Addition to Atorvastatin Compared to Placebo in Subjects With Primary Hypercholesterolemia (Protocol P00692)
This is a multicenter, randomized, double-blind, placebo-controlled, balanced-parallel-group, efficacy and safety trial of ezetimibe coadministered with atorvastatin in adult participants with primary hypercholesterolemia.
The primary hypothesis is that the coadministration of ezetimibe 10 mg/day with atorvastatin (pooled across all doses: 10 mg, 20 mg, 40 mg, 80 mg) will result in a significantly greater reduction in direct low density lipoprotein-cholesterol (LDL-C) when compared with atorvastatin (pooled across all doses: 10 mg, 20 mg, 40 mg, 80 mg) alone and ezetimibe 10 mg alone.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
628
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- If female, is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP), or is a WOCBP who has used a contraceptive consistent with local regulations.
- Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene regimen during the study period.
- Primary hypercholesterolemic participants with a plasma LDL-Cholesterol ≥145 mg/dL (3.75 mmol/L) and ≤250 mg/dL (6.48 mmol/L) and plasma triglyceride ≤350 mg/dL (3.99 mmol/L) after adequate drug washout
- Must be willing to observe the National Cholesterol Education Program (NCEP) Step I diet as determined by a Ratio of Ingested Saturated fat and Cholesterol to Calories (RISCC) score not greater than 24 throughout this study. Ability to complete Diet Diaries needs to be demonstrated.
Exclusion Criteria:
- Has a history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
- Underlying disease likely to limit life span to less than 1 year.
- Participants with hypercholesterolemia in whom withholding of approved lipid-lowering therapy would be inappropriate.
- Have previously been randomized in any of the studies evaluating Ezetimibe (SCH 58235).
- Known hypersensitivity or any contraindication to atorvastatin (LIPITOR®).
- Pregnant or lactating women.
- Congestive heart failure New York Heart Association (NYHA) Class III or IV.
- Uncontrolled cardiac arrhythmias.
- Myocardial infarction, coronary bypass surgery or angioplasty within 6 months of study entry.
- Unstable or severe peripheral artery disease within 3 months of study entry.
- Unstable angina pectoris.
- Disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
- Uncontrolled or newly diagnosed (within 1 month of study entry) diabetes mellitus.
- Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins.
- Known impairment of renal function (plasma creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease.
- Active or chronic hepatobiliary or hepatic disease.
- Participants who are known to be Human Immunodeficiency Virus (HIV) positive.
- Participants with known coagulopathy.
- Lipid-altering agents, other than study drugs for the whole duration of the study.
- Oral corticosteroids.
- Cardiovascular drugs such as: beta blockers, calcium channel blockers, ACE inhibitors, nitrates or α-adrenergic blockers or thiazide diuretics will be allowed, provided the dose remains constant for the duration of the study and the participant has received a stable dose for at least 8 weeks before the initial qualifying LDL-C level is drawn. Aspirin up to 325 mg/day is permitted. In addition, aspirin is allowed as a as needed (prn) concomitant medication.
- Treatment with psyllium or other fiber-based laxatives unless treated with a stable regimen for at least 4 weeks before initial qualifying lipid determination. Dose must remain constant throughout the study period.
- Treatment with troglitazone (Rezulin®) unless treated with a stable regimen for at least 6 weeks before initial qualifying lipid determination. Dose must remain constant throughout the study period.
- Treatment with cyclosporine.
- Use of any investigational drugs within 30 days of study entry.
- Treatment with agents with known drug interaction with atorvastatin including antifungal azoles (itraconazole and ketoconazole), macrolide antibiotics (erythromycin and clarithromycin), and nefazodone. In addition, treatment with other agents that may interfere with or induce the CYP3A4 isoenzyme of the cytochrome P450 system should be avoided.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
Placebo is to be taken orally once a day (QD) in the morning for 12 consecutive weeks.
|
|
ACTIVE_COMPARATOR: Ezetimibe 10 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
|
ACTIVE_COMPARATOR: Atorvastatin 10 mg
Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
|
EXPERIMENTAL: Ezetimibe 10 mg + Atorvastatin 10 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
Other Names:
|
ACTIVE_COMPARATOR: Atorvastatin 20 mg
Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
|
EXPERIMENTAL: Ezetimibe 10 mg + Atorvastatin 20 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
Other Names:
|
ACTIVE_COMPARATOR: Atorvastatin 40 mg
Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
|
EXPERIMENTAL: Ezetimibe 10 mg + Atorvastatin 40 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
Other Names:
|
ACTIVE_COMPARATOR: Atorvastatin 80 mg
Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
|
EXPERIMENTAL: Ezetimibe 10 mg + Atorvastatin 80 mg
Ezetimibe 10 mg (MK-0653, SCH 58235) + Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
|
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change from Baseline at Week 12 of Plasma Low Density Lipoprotein Cholesterol (LDL-C)
Time Frame: Baseline and Week 12
|
Plasma LDL-C determined following a standard ultracentrifugation / precipitation (quantification) procedure (direct LDL-C).
Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change from Baseline at Week 12 for Calculated Low Density Lipoprotein-Cholesterol (LDL-C)
Time Frame: Baseline and Week 12
|
Participants had LDL-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Total Cholesterol (TC)
Time Frame: Baseline and Week 12
|
Participants had TC levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Triglycerides (TG)
Time Frame: Baseline and Week 12
|
Participants had TG levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for High Density-Lipoprotein-Cholesterol (HDL-C)
Time Frame: Baseline and Week 12
|
Participants had HDL-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Apolipoprotein B (Apo B)
Time Frame: Baseline and Week 12
|
Participants had Apo B levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Non-High Density-Lipoprotein-Cholesterol (Non-HDL-C)
Time Frame: Baseline and Week 12
|
Participants had Non-HDL-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for High Density-Lipoprotein 2-Cholesterol (HDL2-C)
Time Frame: Baseline and Week 12
|
Participants had HDL2-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for High Density-Lipoprotein 3-Cholesterol (HDL3-C)
Time Frame: Baseline and Week 12
|
Participants had HDL3-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Apolipoprotein A-I (Apo A-I),
Time Frame: Baseline and Week 12
|
Participants had Apo A1 levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Direct Low Density-Lipoprotein 3-Cholesterol/High Density-Lipoprotein 3-Cholesterol (LDL-C/HDL-C) Ratio
Time Frame: Baseline and Week 12
|
Participants had LDL-C and HDL-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline in the LDL-C/HDL-C ratio was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Direct Total Cholesterol/High Density-Lipoprotein 3-Cholesterol (TC/HDL-C) Ratio
Time Frame: Baseline and Week 12
|
Participants had TC and HDL-C levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline in the TC/HDL-C ratio was calculated.
|
Baseline and Week 12
|
Percent Change from Baseline at Week 12 for Lipoprotein (a) (Lp[a])
Time Frame: Baseline and Week 12
|
Participants had Lp(a) levels assessed at baseline and after 12 weeks of study drug administration.
The percent change from baseline was calculated.
|
Baseline and Week 12
|
The Percentage of Participants Achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP II) Target Goal for Direct Low Density Lipoprotein-Cholesterol (LDL-C)
Time Frame: Week 12
|
LDL cholesterol level goal is <100 mg per deciliter (2.60 mmol per L)
|
Week 12
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
March 6, 2000
Primary Completion (ACTUAL)
July 27, 2001
Study Completion (ACTUAL)
July 27, 2001
Study Registration Dates
First Submitted
March 6, 2019
First Submitted That Met QC Criteria
March 6, 2019
First Posted (ACTUAL)
March 7, 2019
Study Record Updates
Last Update Posted (ACTUAL)
February 17, 2022
Last Update Submitted That Met QC Criteria
February 7, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Hypercholesterolemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
- Ezetimibe
Other Study ID Numbers
- P00692 (OTHER: Schering-Plough Protocol Number)
- MK-0653-013 (OTHER: Merck Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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