Target-Mediated Modeling of Alirocumab in Adolescents and Children ≥8 to <12 Years of Age Using Phase II and III Data

Abstract

A population pharmacokinetic (PK) covariate analysis was conducted utilizing data from adolescents and children ≥8 to <12 years of age with heterozygous familial hypercholesterolemia. One phase II and 1 phase III study were analyzed (121 patients on active treatment). A 2-compartment target-mediated model with linear and target-mediated elimination and transit compartments describing lag time in absorption was utilized. Weight and high-dose statins were statistically significant covariate. Except for the central volume, estimated population PK parameters describing linear kinetics were similar across pediatric patients and healthy adults. Coadministration of concomitant high doses of statins was associated with an increase in the production rate of proprotein convertase subtilisin/kexin type 9. The primary covariate model adequately described alirocumab PKs in the pediatric population. The analysis supports the recommended weight-adjusted subcutaneous dosing regimens for alirocumab in children with heterozygous hypercholesterolemia aged ≥8 years.