Modeling and Simulation Approach to Pediatric Drug Development

Authors: Grasela TH, Passarell JA, Ludwig E, Fiedler-Kelly J
Conference: PAGE
Keywords: breakpoint model, children, clinical trial, dose, dosing regimens, exposure, PD, Pediatric, pediatrics, pharmacodynamic, pharmacokinetic, PK, PK/PD, PKPD methodology, simulation, strategy, study design
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Purpose: Describe a process for determining pediatric drug doses using pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulation.

Methods: Using a PK model, 3 alternative dosage regimens were identified for Drug X. Drug exposures after administration of these regimens were simulated. Individual patient outcomes were then simulated using a PK/PD model.

Results: All of the 3 simulated regimens were found to provide pediatric patients with AUC0-24 values comparable to those seen previously in adults. Clinical trial simulations showed that the trial success rate ranged from 34% to 88% using a breakpoint model. The trial success rate increased with increasing number of baseline clinical episodes per week.

Conclusions: Improvements in design of future pediatric clinical trials to support PK/PD modeling and simulation would facilitate selection of appropriate dosing regimens in children. Furthermore, the application of this approach may support the objectives of the European Union (EU) Pediatric Regulation.

Population Approach Group in Europe (PAGE), St. Petersburg, Russia, June 2009

By Thaddeus Grasela, Julie Passarell, Elizabeth Ludwig, Jill Fiedler-Kelly