Colesevelam Hydrochloride: Efficacy and Safety in Pediatric Subjects with Heterozygous Familial Hypercholesterolemia

• Published in: The Journal of pediatrics Vol. 156; no. 2; pp. 231 - 236.e3
• Main Authors: Stein, Evan A., MD, PhD, Marais, A. David, MD, Szamosi, Tamas, MD, PhD, Raal, Frederick J., MD, PhD, Schurr, Daniel, MD, Urbina, Elaine M., MD, Hopkins, Paul N., MD, MSPH, Karki, Sulekha, BAMS, Xu, Jianbo, MS, Misir, Soamnauth, PharmD, Melino, Michael, PhD
• Format: Journal Article
• Language: English
• Published: Maryland Heights, MO Mosby, Inc 01.02.2010; Elsevier
• Subjects: Adolescent; Allylamine - adverse effects; Allylamine - analogs & derivatives; Allylamine - pharmacology; Allylamine - therapeutic use; Anticholesteremic Agents - adverse effects; Anticholesteremic Agents - pharmacology; Anticholesteremic Agents - therapeutic use; Biological and medical sciences; Child; Cholesterol, LDL - blood; Cholesterol, LDL - drug effects; Colesevelam Hydrochloride; Disorders of blood lipids. Hyperlipoproteinemia; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; General aspects; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hyperlipoproteinemia Type II - drug therapy; Male; Medical sciences; Metabolic diseases; Pediatrics; cIMT; AE; NCEP; LOCF; Adverse event; Last observation carried forward; Heterozygous familial hypercholesterolemia; Upper limit of normal; heFH; HCl; Hydrochloride; Low-density lipoprotein; HDL; High-density lipoprotein; LDL; SAE; ULN; Carotid intima-media thickness; Serious adverse event; National Cholesterol Education Program; Human; Pediatrics; Toxicity; Treatment efficiency; Metabolic diseases; Polymer; Lipids; Hyperlipoproteinemia; Lipoprotein; Cholesterol; Colesevelam; Heterozygosity; Genetic disease; Hypercholesterolemia; Hydrochlorides; Safety; Dyslipemia; Child; Antilipemic agent
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2009.08.037

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.