Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia.

Abstract

OBJECTIVE:

Evaluate the efficacy and safety of colesevelam hydrochloride in children with heterozygous familial hypercholesterolemia (heFH).

STUDY DESIGN:

This was a randomized, double-blind, 41-site study in 194 children aged 10 to 17 years (inclusive) with heFH (statin-naïve or on a stable statin regimen). After a 4-week stabilization period (period I), subjects were randomized 1:1:1 to placebo, colesevelam 1.875 g/d, or colesevelam 3.75 g/d for 8 weeks (period II). All then received open-label colesevelam 3.75 g/d for 18 weeks (period III), with follow-up 2 weeks later. The primary endpoint was percent change in low-density lipoprotein (LDL)-cholesterol from baseline to week 8. Secondary endpoints included percent change in other lipoprotein variables, including non-high-density lipoprotein (non-HDL)-cholesterol. Adverse events were also evaluated.

RESULTS:

At week 8, a significant difference from baseline in LDL-cholesterol was reported with colesevelam 1.875 g/d (-6.3%; P = .031) and colesevelam 3.75 g/d (-12.5%; P < .001) compared with placebo. Significant treatment effects were also reported for total cholesterol (-7.4%), non-HDL-cholesterol (-10.9%), HDL-cholesterol (+6.1%), apolipoprotein A-I (+6.9%), and apolipoprotein B (-8.3%) and a nonsignificant effect for triglycerides (+5.1%) with colesevelam 3.75 g/d compared with placebo at week 8. These treatment effects were maintained during period III.

CONCLUSIONS:

Colesevelam significantly lowered LDL-cholesterol levels in children with heFH.

• Authors: Evan A Stein, A David Marais, Tamas Szamosi, Frederick J Raal, Daniel Schurr, Elaine M Urbina, Paul N Hopkins, Sulekha Karki, Jianbo Xu, Soamnauth Misir, Michael Melino
• Journal: The Journal of pediatrics (J Pediatr) Vol. 156 Issue 2 Pg. 231-6.e1-3 (Feb 2010) ISSN: 1097-6833 [Electronic] United States
• PMID: 19879596 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Mosby, Inc. All rights reserved.

Chemical References

• Anticholesteremic Agents
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Allylamine
• Colesevelam Hydrochloride

Topics

• Adolescent
• Allylamine (adverse effects, analogs & derivatives, pharmacology, therapeutic use)
• Anticholesteremic Agents (adverse effects, pharmacology, therapeutic use)
• Child
• Cholesterol, LDL (blood, drug effects)
• Colesevelam Hydrochloride
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Drug-Related Side Effects and Adverse Reactions
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage)
• Hyperlipoproteinemia Type II (drug therapy)
• Male