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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: ezetimibe with simvastatin
* Drug: simvastatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pooled subjects who received ezetimibe with simvastatin<br>Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg | Drug: ezetimibe with simvastatin<br>* 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<br>|
| Active Comparator: Pooled subjects who received simvastatin monotherapy<br>Pooled subjects who received ezetimibe matching placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg | Drug: simvastatin<br>* 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<br>|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholesterol, drugs, hypercholesterolemia, adolescent, randomized controlled trials