Dose Selection for Fremanezumab (AJOVY) Phase 3 Pediatric Migraine Studies Using Pharmacokinetic Data From a Pediatric Phase 1 Study and a Population Pharmacokinetic Modeling and Simulation Approach

Authors: Cohen-Barak O, Radivojevic A, Jones A, Fiedler-Kelly J, Gillespie M, Brennan M, Gutman D, Rasamoelisolo M, Hallak H, Loupe P, Kessler Y, Ning X, Levi M, Ahn AH, Rabinovich-Guilatt L
Publication: Cephalalgia
Keywords: calcitonin-gene-related peptide, CGRP, fremanezumab, migraine, pediatric dosing, population pharmacokinetics
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Background
Potential fremanezumab doses for pediatric patients were evaluated using pharmacokinetic modeling and simulation. An open-label phase 1 pharmacokinetic and safety study was conducted in pediatric patients with migraine. This study’s results together with refinement of the adult population pharmacokinetic model were used to determine fremanezumab dose recommendations for phase 3 pediatric studies.

Methods
Initial application of the adult model suggested that a 75 mg dose in pediatric patients would match exposures determined safe and efficacious in adults; thus, in the phase 1 study, 15 patients, aged 6–11 years and weighing 17–45 kg received a single subcutaneous 75 mg fremanezumab dose. The sparse pharmacokinetic data collected were used to refine the adult model and simulate concentration-time profiles for monthly subcutaneous doses (60 to 225 mg) in a virtual pediatric population.

By Orit Cohen-Barak, Andrijana Radivojevic, Aksana Jones, Jill Fiedler-Kelly, Michael Gillespie, Michael Brennan, Dikla Gutman, Michele Rasamoelisolo, Hussein Hallak, Pippa Loupe, Yoel Kessler, Xiaoping Ning, Micha Levi, Andrew H Ahn, Laura Rabinovich-Guilatt