Dose Selection Based on Modeling and Simulation for Rivipansel in Pediatric Patients Aged 6 to 11 Years With Sickle Cell Disease.

Abstract

This modeling and simulation exercise aimed to provide dosing recommendations for rivipansel phase III studies in children aged 6–11 years with sickle cell disease (SCD). Pharmacokinetic data from 109 patients aged 12–51 years who received rivipansel (2–40 mg/kg) in previous studies (three phase I and one phase II) were integrated to build a three‐compartmental simulation model. Renal clearance simulations across the age range accounted for renal function development and postulated hyperfiltration in SCD. Simulated demographic distributions for the pediatric SCD population were used to predict concentration‐time profiles from three dosing regimens, which were then compared against efficacious average steady‐state concentrations observed in phase II. A dosing regimen comprising a 40‐mg/kg loading dose followed by a 20‐mg/kg maintenance dose every 12 hours was selected, as it will likely provide an efficacious concentration range. Its validity will be confirmed in the ongoing phase III study.