The PK of a sponsor’s candidate has been studied in a pediatric population, but is relatively unknown in an adult population. Due to the desired PK characteristics of the treatment (rapid onset of efficacy, sustained concentrations throughout the majority of the day, but drop in stimulant effect at night so that the patient can sleep), the sponsor is also developing an extended release formulation. With the unknown adult PK properties and the desire to optimize the PK profile with alternative formulations, the sponsor came to us to develop a modeling and simulation strategy.
We adapted the pediatric population PK model using allometric scaling to allow estimation of the adult PK profiles. The adult model was verified against the only clinical PK parameters in adults that was found in the literature. In order to determine the optimal formulation, simulations were conducted using Weibull absorption based on dissolution testing results. Once the formulation was selected, the simulations were also used to guide the clinical study design for a food effect study and a proof of concept study.
The proof of concept study had a positive outcome, so the sponsor is currently seeking interested parties in licensing the drug. The work on the formulations was included in a patent that was filed in 2016.