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)

NCT03867110 | Completed Phase 3 FDA Drug

• 2 other identifiers: P00692MK-0653-013
• Study Type: interventional
• Target: 628
• Locations: 0 countries
• Sites: N/A

Brief 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

Hypercholesterolemia

Keywords

Hypercholesterolemia; Ezetimibe; Atorvastatin; Low density lipoprotein-cholesterol

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and Week 12

Secondary Outcomes (13)

• Percent Change from Baseline at Week 12 for Calculated Low Density Lipoprotein-Cholesterol (LDL-C)

  Baseline and Week 12

• Percent Change from Baseline at Week 12 for Total Cholesterol (TC)

  Baseline and Week 12

• Percent Change from Baseline at Week 12 for Triglycerides (TG)

  Baseline and Week 12

• Percent Change from Baseline at Week 12 for High Density-Lipoprotein-Cholesterol (HDL-C)

  Baseline and Week 12

• Percent Change from Baseline at Week 12 for Apolipoprotein B (Apo B)

  Baseline and Week 12

Study Arms (10)

Placebo

PLACEBO COMPARATOR

Placebo is to be taken orally once a day (QD) in the morning for 12 consecutive weeks.

Drug: Placebo

Ezetimibe 10 mg

ACTIVE COMPARATOR

Ezetimibe 10 mg (MK-0653, SCH 58235) is to be taken orally QD in the morning for 12 consecutive weeks.

Drug: Ezetimibe 10 mg

Atorvastatin 10 mg

ACTIVE COMPARATOR

Atorvastatin 10 mg is to be taken orally QD in the morning for 12 consecutive weeks.

Drug: Atorvastatin 10 mg

Ezetimibe 10 mg + Atorvastatin 10 mg

EXPERIMENTAL

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

Atorvastatin 20 mg

ACTIVE COMPARATOR

Atorvastatin 20 mg is to be taken orally QD in the morning for 12 consecutive weeks.

Drug: Atorvastatin 20 mg

Ezetimibe 10 mg + Atorvastatin 20 mg

EXPERIMENTAL

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

Atorvastatin 40 mg

ACTIVE COMPARATOR

Atorvastatin 40 mg is to be taken orally QD in the morning for 12 consecutive weeks.

Drug: Atorvastatin 40 mg

Ezetimibe 10 mg + Atorvastatin 40 mg

EXPERIMENTAL

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

Atorvastatin 80 mg

ACTIVE COMPARATOR

Atorvastatin 80 mg is to be taken orally QD in the morning for 12 consecutive weeks.

Drug: Atorvastatin 80 mg

Ezetimibe 10 mg + Atorvastatin 80 mg

EXPERIMENTAL

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

Placebo DRUG

Placebo

Ezetimibe 10 mg DRUG

Also known as: MK-0653, SCH 58235, ZETIA®

Ezetimibe 10 mg; Ezetimibe 10 mg + Atorvastatin 10 mg; Ezetimibe 10 mg + Atorvastatin 20 mg; Ezetimibe 10 mg + Atorvastatin 40 mg; Ezetimibe 10 mg + Atorvastatin 80 mg

Atorvastatin 10 mg DRUG

Also known as: LIPITOR®

Atorvastatin 10 mg; Ezetimibe 10 mg + Atorvastatin 10 mg

Atorvastatin 20 mg DRUG

Also known as: LIPITOR®

Atorvastatin 20 mg; Ezetimibe 10 mg + Atorvastatin 20 mg

Atorvastatin 40 mg DRUG

Also known as: LIPITOR®

Atorvastatin 40 mg; Ezetimibe 10 mg + Atorvastatin 40 mg

Atorvastatin 80 mg DRUG

Also known as: LIPITOR®

Atorvastatin 80 mg; Ezetimibe 10 mg + Atorvastatin 80 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• 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.

  PMID: 12719279 RESULT

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Ezetimibe; Atorvastatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 7, 2019
• Study Start: March 6, 2000
• Primary Completion: July 27, 2001
• Study Completion: July 27, 2001
• Last Updated: May 10, 2024

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share