A Study of SCH 58235 (Ezetimibe) When Added to Ongoing Therapy With a Statin in Participants With Primary Hypercholesterolemia, Known Coronary Heart Disease, or Multiple Cardiovascular Risk Factors (P02173)

NCT03882905 | Completed Phase 3 FDA Drug

• 3 other identifiers: P02173MK-0653-001SCH 58235 P02173
• Study Type: interventional
• Target: 769
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study to evaluate the lipid-altering efficacy, safety, and tolerability of ezetimibe when added to ongoing therapy with an 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) in participants with primary hypercholesterolemia, multiple cardiovascular risk factors, or known coronary heart disease (CHD) or CHD-equivalent disease. The statin and dose in use by the participant at screening will be maintained at the same dose for the 8-week treatment phase of the study. Following the treatment, there will be a 6-week cholesterol reversibility phase to determine the rebound effect on cholesterol after ezetimibe is discontinued, but the participant is still on their statin therapy. The primary hypothesis is that the addition of ezetimibe 10 mg/day to ongoing statin monotherapy will result in a further reduction in low-density lipoprotein-cholesterol (LDL-C) compared with placebo. The protocol was amended to include an extension for participants who complete the base study. The extension will evaluate the safety and tolerability of concomitant treatment of simvastatin with ezetimibe10 mg/day over a 1-year period. All participants in the extension will be converted from current statin to an equivalent dose of simvastatin for 6 weeks. Participants then will be randomly assigned to receive simvastatin coadministered with either with Ezetimibe 10 mg daily or matching placebo for the reminder of study.

Conditions

Primary Hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

• Percentage Change from Baseline in LDL-C: Base Study

  Baseline and Week 8 of Base Study

• Percentage Participants with Consecutive Elevations ≥3 x Upper Limit of Normal (ULN) in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT): Extension

  up to 48 weeks (Extension)

Secondary Outcomes (12)

• Percentage of Participants Achieving LDL-C National Cholesterol Education Program (NCEP) Adult Treatment Program II (ATP II) Target Levels: Base Study

  Week 8 of Base Study

• Percentage Change from Baseline in Total Cholesterol (TC) : Base Study

  Baseline and Week 8 of Base Study

• Percentage Change from Baseline in Triglycerides (TG): Base Study

  Baseline and Week 8 of Base Study

• Percentage Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) : Base Study

  Baseline and Week 8 of Base Study

• Percentage Change from Baseline in Non-HDL-C: Base Study

  Baseline and Week 8 of Base Study

Study Arms (4)

Ezetimibe: Base Study

EXPERIMENTAL

10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks.

Drug: Ezetimibe; Drug: Statin

Placebo: Base Study

PLACEBO COMPARATOR

Placebo for ezetimibe 10-mg tablet, oral taken once daily concomitantly with the participant' s current statin therapy for 8 weeks.

Drug: Placebo; Drug: Statin

Ezetimibe: Extension

EXPERIMENTAL

10-mg tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.

Drug: Ezetimibe; Drug: Simivastatin

Placebo: Extension

PLACEBO COMPARATOR

Placebo for ezetimibe tablet, oral taken once daily concomitantly with simvastatin for 48 weeks.

Drug: Placebo; Drug: Simivastatin

Interventions

Ezetimibe DRUG

10 mg tablet, oral, once daily

Ezetimibe: Base Study; Ezetimibe: Extension

Placebo DRUG

one tablet, oral, once daily

Placebo: Base Study; Placebo: Extension

Simivastatin DRUG

Once daily administration at dose to be determined

Ezetimibe: Extension; Placebo: Extension

Statin DRUG

Statin administered orally once daily at dose determined by treatment prior to enrollment by personal physician

Ezetimibe: Base Study; Placebo: Base Study

Eligibility Criteria

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

You may qualify if:

• Currently taking an approved and stable (for at least 6 weeks prior to screening) daily dose of a statin and by history had taken \>80% of daily doses for the preceding 6 weeks
• Have a negative pregnancy test
• Agree to practice an effective barrier method of birth control during the study if of childbearing potential
• Females receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, maintain a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study
• Must verify previous instruction on an National Cholesterol Education Program (NCEP) Step 1 diet or similar diet and must maintain a stable diet regimen for the duration of the study

You may not qualify if:

• History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy
• Previously enrolled to any study evaluating ezetimibe
• Pregnant or lactating
• Consumes greater than 14 alcoholic drinks/week
• Taking a lipid-altering agent (other than statins) in previous 6 weeks
• Taking Oral corticosteroids, unless the corticosteroids were for replacement therapy to treat pituitary/adrenal disease and were treated with a stable regimen for at least the previous 6 weeks
• Treatment with psyllium, other fiber-based laxatives, and other over-the-counter (OTC) therapies that affect serum lipids, unless treated with a stable regimen for at least 6 weeks
• Taking orlistat
• Taking cyclosporine
• Use of any investigational drugs within 30 days
• Treatment with agents with known interactions with statins including antifungal azoles (itraconazole and ketoconazole), macrolide antibiotics (erythromycin and clarithromycin) and nefazodone or with other potent agents that could significantly interfere with cytochrome P-450 system
• Congestive heart failure New York Heart Association (NYHA) Class III or IV
• Uncontrolled cardiac arrhythmias
• Myocardial infarction, coronary artery bypass surgery or angioplasty within 3 months
• Unstable or severe peripheral artery disease within 3 months

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (2)

• Masana L, Mata P, Gagne C, Sirah W, Cho M, Johnson-Levonas AO, Meehan A, Troxell JK, Gumbiner B; Ezetimibe Study Group. Long-term safety and, tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005 Feb;27(2):174-84. doi: 10.1016/j.clinthera.2005.02.011.

  PMID: 15811480 RESULT

• Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, Cho M, Musliner TA, Gumbiner B; Ezetimibe Study Group. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002 Nov 15;90(10):1084-91. doi: 10.1016/s0002-9149(02)02774-1.

  PMID: 12423708 RESULT

MeSH Terms

Interventions

Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

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 19, 2019
• First Posted: March 20, 2019
• Study Start: January 31, 2001
• 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