Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579)

Efficacy, Safety, and Tolerability of Ezetimibe in Coadministration With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia

This is a randomized, double-blind, controlled, parallel-group, multicenter, Phase-3 study to evaluate the efficacy and safety of ezetimibe with simvastatin taken alone in subjects ages 10-17 years with Heterozygous Familial Hypercholesterolemia.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: ezetimibe with simvastatin; Drug: simvastatin

Detailed Description

This study consisted of 3 distinct periods. In Period 1, subjects received daily treatment for 6 weeks as part of either the ezetimibe with simvastatin group or part of the simvastatin monotherapy group. Subjects in the ezetimibe with simvastatin group received one of three treatments: coadministration of ezetimibe 10 mg/day plus simvastatin 10 mg/day, 20 mg/day, or 40 mg/day. Subjects in the simvastatin monotherapy group received one of three treatments: ezetimibe placebo plus simvastatin 10 mg/day, 20 mg/day, or 40 mg/day. The primary and key secondary efficacy analysis were based on the evaluations performed during Period 1 and were presented as data for subjects pooled from either the ezetimibe with simvastatin treatment groups compared with data for subjects pooled from the simvastatin monotherapy treatment groups.

In Period 2, subjects received ezetimibe 10 mg/day plus simvastatin 40 mg/day or ezetimibe placebo plus simvastatin 40 mg/day for 27 additional weeks maintaining the same treatment assignment (coadministration vs monotherapy) as in Period 1.

In Period 3, all subjects received ezetimibe 10 mg/day plus open-label simvastatin daily for 20 weeks.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adolescent (ages 10 - 17 years) boys or girls weighing at least 88 lbs (40 kg).
• Subjects must have high cholesterol (low density lipoprotein cholesterol [LDL-C] more than 159 mg/dL or 4.1 mmol/L) and a family history of high cholesterol.

Exclusion Criteria:

• Subjects diagnosed with delayed puberty.
• Subjects who are sensitive to simvastatin and/or ezetimibe.
• Subjects who drink alcohol excessively or who have a history of alcohol or drug abuse within the past 2 years.
• Subjects who are known to be HIV positive, are undergoing LDL apheresis or plasma apheresis, or have had a partial ileal bypass.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pooled subjects who received ezetimibe with simvastatin; Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg	Drug: ezetimibe with simvastatin; Ezetimibe 10 mg plus simvastatin 10 mg once a day for six weeks, or Ezetimibe 10 mg plus simvastatin 20 mg once a day for six weeks, or Ezetimibe 10 mg plus simvastatin 40 mg once a day for six weeks
Active Comparator: Pooled subjects who received simvastatin monotherapy; Pooled subjects who received ezetimibe matching placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg	Drug: simvastatin; Ezetimibe matching placebo plus simvastatin 10 mg once a day for six weeks, or Ezetimibe matching placebo plus simvastatin 20 mg once a day for six weeks, or Ezetimibe matching placebo plus simvastatin 40 mg once a day for six weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	Least squares mean percent change from Baseline in LDL-C at the end of Step 1 (Week 6) in the pooled groups who received ezetimibe plus simvastatin compared with pooled groups who received simvastatin monotherapy	baseline to 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Total Cholesterol (TC)	baseline to 6 weeks
Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C)	baseline to 6 weeks
Percent Change From Baseline in Triglycerides (TG)	baseline to 6 weeks
Percent Change From Baseline in Apolipoprotein B (Apo B)	baseline to 6 weeks
Percent Change From Baseline in HDL-C	baseline to 6 weeks

Collaborators and Investigators

• Sponsor: Organon and Co
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagne C, Shi G, Veltri E, Avis HJ, Kastelein JJ. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol. 2008 Oct 21;52(17):1421-9. doi: 10.1016/j.jacc.2008.09.002.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): June 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: August 9, 2005
• First Submitted That Met QC Criteria: August 9, 2005
• First Posted (Estimate): August 11, 2005

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: adolescent; hypercholesterolemia; cholesterol; drugs; randomized controlled trials
• 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; Simvastatin; Ezetimibe
• Other Study ID Numbers: P02579; EUDRACT NUMBER:2004-002627-40;; SCH 58235;; DOC ID 2526810