Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia.
OBJECTIVE
Evaluate the efficacy and safety of colesevelam hydrochloride in children with heterozygous familial hypercholesterolemia (heFH).


METHODS
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.
Stein
Evan A
EA
Metabolic and Atherosclerosis Research Center, 4685 Forest Ave., Suite A, Cincinnati, OH 45212, USA. ESteinMRL@aol.com
Marais
A David
AD
Szamosi
Tamas
T
Raal
Frederick J
FJ
Schurr
Daniel
D
Urbina
Elaine M
EM
Hopkins
Paul N
PN
Karki
Sulekha
S
Xu
Jianbo
J
Misir
Soamnauth
S
Melino
Michael
M
D000293:Adolescent; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D000069472:Colesevelam Hydrochloride; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008297:Male
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000499:Allylamine; D000069472:Colesevelam Hydrochloride