Population pharmacokinetics of eptinezumab in paediatric patients with migraine and dose selection for phase 3 paediatric migraine studies.

This population pharmacokinetics (PopPK) analysis of eptinezumab used data from a paediatric study and a prior adult PopPK model to compare eptinezumab pharmacokinetics between adult and paediatric populations to determine dose recommendations for the phase 3 paediatric studies in migraine. The data consisted of 16 adolescents and 12 children with migraine, with corresponding demographics and 278 plasma concentrations in total. PopPK analysis was performed through nonlinear mixed effect modelling and with prior knowledge taken from a previous PopPK model in adults. A two-compartment model-adjusted for body weight impact on clearances and volumes of distributions and scaled to the power of 0.75 and 1.0, respectively-was found to adequately describe the paediatric pharmacokinetic data. The simulated population showed overlap in area under the plasma concentration-time curve and maximum plasma concentration between the paediatric and adult populations, with paediatric exposures within 10%-15% above adult levels on average. To provide comparable exposure to the approved adult doses, weight-based dosing adjustments are recommended for paediatric patients weighing ≤40 kg, while no adjustments are needed for patients weighing >40 kg. These results support the dosing strategy being used in the ongoing efficacy and safety studies with eptinezumab in children and adolescents with migraine.