Base and Covariate Population Pharmacokinetic Analyses of Dupilumab in Adolescents and Children ≥6 to <12 Years of Age Using Phase 3 Data

Abstract

Population pharmacokinetic (PK) base and covariate analyses were conducted using data from adolescents with moderate-to-severe atopic dermatitis (AD) and children ≥6 to <12 years of age with severe AD. Two phase 3 studies were analyzed (165 adolescents and 241 children on active treatment). A 2-compartment model with linear and Michaelis-Menten elimination and 3 transit compartments describing lag time in absorption was utilized. Weight, albumin, body mass index, and Eczema Area and Severity Index score were statistically significant covariates in at least 1 of the age populations. Only body weight had a consequential effect on central volume. Although an absorption rate and target-mediated clearance somewhat decreased with age, no dose adjustment was needed in addition to the adjustment for weight already implemented in the phase 3 studies. Otherwise, population PK parameters and covariates were similar across the 2 pediatric subpopulations and in adults. No allometric changes in elimination rate and beta half-life were observed with weight. Parameterization of models in terms of rates was a useful alternative to parameterization in terms of clearances, allowing for an absence of repeated covariates and preventing overparameterization. The model adequately described dupilumab pharmacokinetics in the pediatric populations.

Keywords: adolescents; atopic dermatitis; children; dupilumab; population pharmacokinetics.