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)

May 8, 2024 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
628

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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 Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Placebo is to be taken orally once a day (QD) in the morning for 12 consecutive weeks.
Drug: Placebo
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.
Drug: Ezetimibe 10 mg
Other Names:
  • MK-0653
  • SCH 58235
  • ZETIA®
Active Comparator: Atorvastatin 10 mg
Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Drug: Atorvastatin 10 mg
Other Names:
  • LIPITOR®
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.
Drug: Ezetimibe 10 mg
Other Names:
  • MK-0653
  • SCH 58235
  • ZETIA®
Drug: Atorvastatin 10 mg
Other Names:
  • LIPITOR®
Active Comparator: Atorvastatin 20 mg
Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Drug: Atorvastatin 20 mg
Other Names:
  • LIPITOR®
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.
Drug: Ezetimibe 10 mg
Other Names:
  • MK-0653
  • SCH 58235
  • ZETIA®
Drug: Atorvastatin 20 mg
Other Names:
  • LIPITOR®
Active Comparator: Atorvastatin 40 mg
Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Drug: Atorvastatin 40 mg
Other Names:
  • LIPITOR®
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.
Drug: Ezetimibe 10 mg
Other Names:
  • MK-0653
  • SCH 58235
  • ZETIA®
Drug: Atorvastatin 40 mg
Other Names:
  • LIPITOR®
Active Comparator: Atorvastatin 80 mg
Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.
Drug: Atorvastatin 80 mg
Other Names:
  • LIPITOR®
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.
Drug: Ezetimibe 10 mg
Other Names:
  • MK-0653
  • SCH 58235
  • ZETIA®
Drug: Atorvastatin 80 mg
Other Names:
  • LIPITOR®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Organon and Co

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Merck Sharp & Dohme LLC

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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 6, 2000

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 27, 2001

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 27, 2001

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 10, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P00692 (Other Identifier: Schering-Plough Protocol Number)
  • MK-0653-013 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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