CompletedNCT03867110Updated May 10, 2024

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)

A Phase 3 interventional study of Placebo and Ezetimibe 10 mg in Hypercholesterolemia, sponsored by Organon and Co. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-05-10.

Sponsored by Organon and Co · Phase 3, Interventional, and Treatment

From the registry’s dates

Primary completion was Jul 2001, 25 years 2 months ago, and no results have been posted to the registry.
Registered 19 years after the study started (first participant enrolled Mar 2000, registered Mar 2019).

Phase: Phase 3
Study type: Interventional
Enrollment: 628
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Conditions studied

Hypercholesterolemia

Browse trials for

Hypercholesterolemia 1,238

Keywords

Hypercholesterolemia
Ezetimibe
Atorvastatin
Low density lipoprotein-cholesterol

In context

Hypercholesterolemia

1,238 studies on the registry are indexed under Hypercholesterolemia; 109 are open to participants now.

This study's enrollment of 628 is above the median of 99 across 991 interventional studies indexed under Hypercholesterolemia.

Browse Hypercholesterolemia studies →

Lead sponsor

Organon and Co is the lead sponsor of 478 studies on the registry; none are open to participants now.

Of its 21 completed or terminated interventional studies of FDA-regulated products, 17 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 628 participants (actual)

Study arms

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
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
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 · Drug: Atorvastatin 10 mg
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
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 · Drug: Atorvastatin 20 mg
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
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 · Drug: Atorvastatin 40 mg
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
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 · Drug: Atorvastatin 80 mg

Interventions

DrugPlacebo
DrugEzetimibe 10 mg
Also known as: MK-0653, SCH 58235, ZETIA®
DrugAtorvastatin 10 mg
Also known as: LIPITOR®
DrugAtorvastatin 20 mg
Also known as: LIPITOR®
DrugAtorvastatin 40 mg
Also known as: LIPITOR®
DrugAtorvastatin 80 mg
Also known as: LIPITOR®

What researchers measure

Primary outcomes

Percent Change from Baseline at Week 12 of Plasma Low Density Lipoprotein Cholesterol (LDL-C)
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.
Time frame: Baseline and Week 12

Secondary outcomes

Percent Change from Baseline at Week 12 for Calculated Low Density Lipoprotein-Cholesterol (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.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Total Cholesterol (TC)
Participants had TC levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Triglycerides (TG)
Participants had TG levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for High Density-Lipoprotein-Cholesterol (HDL-C)
Participants had HDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Apolipoprotein B (Apo B)
Participants had Apo B levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Non-High Density-Lipoprotein-Cholesterol (Non-HDL-C)
Participants had Non-HDL-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for High Density-Lipoprotein 2-Cholesterol (HDL2-C)
Participants had HDL2-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for High Density-Lipoprotein 3-Cholesterol (HDL3-C)
Participants had HDL3-C levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Apolipoprotein A-I (Apo A-I),
Participants had Apo A1 levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: 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
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.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Direct Total Cholesterol/High Density-Lipoprotein 3-Cholesterol (TC/HDL-C) Ratio
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.
Time frame: Baseline and Week 12
Percent Change from Baseline at Week 12 for Lipoprotein (a) (Lp[a])
Participants had Lp(a) levels assessed at baseline and after 12 weeks of study drug administration. The percent change from baseline was calculated.
Time frame: 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)
LDL cholesterol level goal is \<100 mg per deciliter (2.60 mmol per L)
Time frame: Week 12

Study locations

No study locations are listed for this record.

References and documents

Publications

Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP; Ezetimibe Study Group. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15. doi: 10.1161/01.CIR.0000068312.21969.C8. Epub 2003 Apr 28. PubMed 12719279 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 10, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03867110
Lead sponsor: Organon and Co
Responsible party: Sponsor
First posted: Mar 7, 2019
Start date: Mar 6, 2000
Primary completion: Jul 27, 2001
Completion: Jul 27, 2001
Last update: May 10, 2024

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2022. You cannot join it, but the record below documents what was studied.

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