Clinical trial NCT00129402: Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579)
Official title: Efficacy, Safety, and Tolerability of Ezetimibe in Coadministration With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: cholesterol
drugs
hypercholesterolemia
adolescent
randomized controlled trials
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2005-08-11
Enrollment: 248
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: baseline to 6 weeks
Secondary outcomes:
measure: Percent Change From Baseline in Total Cholesterol (TC)
timeFrame: baseline to 6 weeks
measure: Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C)
timeFrame: baseline to 6 weeks
measure: Percent Change From Baseline in Triglycerides (TG)
timeFrame: baseline to 6 weeks
measure: Percent Change From Baseline in Apolipoprotein B (Apo B)
timeFrame: baseline to 6 weeks
measure: Percent Change From Baseline in HDL-C
timeFrame: baseline to 6 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: 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.