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

Phase 3
Completed
Conditions
Hypercholesterolemia
Interventions
Registration Number
NCT00129402
Lead Sponsor
Organon and Co
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
248
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pooled subjects who received ezetimibe with simvastatinezetimibe with simvastatinPooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Pooled subjects who received simvastatin monotherapysimvastatinPooled subjects who received ezetimibe matching placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)baseline to 6 weeks

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

Secondary Outcome Measures
NameTimeMethod
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-Cbaseline to 6 weeks
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