Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579)(COMPLETED) - Full Text View

Sponsor:	Schering-Plough
Collaborator:	Merck
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00129402

Purpose

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.

Condition	Intervention	Phase
Hypercholesterolemia	Drug: ezetimibe with simvastatin Drug: simvastatin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Efficacy, Safety, and Tolerability of Ezetimibe in Coadministration With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis hypercholesterolemia

MedlinePlus related topics: Cholesterol

Drug Information available for: Simvastatin Ezetimibe

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]
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:

Percent Change From Baseline in Total Cholesterol (TC) [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]
Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C) [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]
Percent Change From Baseline in Triglycerides (TG) [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]
Percent Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]
Percent Change From Baseline in HDL-C [ Time Frame: baseline to 6 weeks ] [ Designated as safety issue: No ]

Enrollment:	248
Study Start Date:	August 2005
Study Completion Date:	June 2007

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	10 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided by Schering-Plough

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagné 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.

Responsible Party:	Head, Clinical Trials Registry & Results Disclosure Group, Schering-Plough
ClinicalTrials.gov Identifier:	NCT00129402 History of Changes
Other Study ID Numbers:	P02579, EUDRACT NUMBER:2004-002627-40;, SCH 58235;, DOC ID 2526810
Study First Received:	August 9, 2005
Results First Received:	January 14, 2010
Last Updated:	March 17, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Schering-Plough:

cholesterol
drugs
hypercholesterolemia
adolescent
randomized controlled trials

Additional relevant MeSH terms:

Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Simvastatin

Ezetimibe
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012