To assess the pharmacokinetics (PK) of XEN901 pediatric formulation (granules), the impact of food (high-fat meal) on this formulation, and its relative bioavailability to an adult immediate-release (IR) tablet formulation.

XEN901 is a potent and highly selective Na_V1.6 inhibitor currently in clinical development for the treatment of adult focal seizures and SCN8A (gain of function) developmental epileptic encephalopathy (SCN8A-DEE). We have developed a pediatric-friendly formulation of XEN901 to enable a proof of concept study in pediatric patients with SCN8A-DEE. Prior to this human bioavailability study, we evaluated the suitability of the pediatric formulation in dogs. 

In this single center, open-label, randomized study, 24 subjects (8 per arm) received XEN901 adult IR tablet or pediatric formulation in a fasted or fed state (high-fat meal) in a 3-period, 3-sequence crossover design. XEN901 was specially formulated as IR granules suitable for pediatric use (see Xenon’s abstract on XEN901 formulation).

Pervious dog PK study demonstrated that in vivo performance of the pediatric formulation in dogs was comparable with pediatric formulation. Subsequently, a 50 mg dose was used in this adult PK study based on the PK and safety data available from an earlier Phase 1 study. In addition, based on the data obtained from the Phase 1 study, it was determined that a 3-period, 3-sequence crossover design was the most efficient design to generate adequate PK data for the initiation of a proof-of-concept study in patients with SCN8A-DEE. This study is ongoing and the results will be available for presentation.

The results from this study are expected to provide useful PK and safety data to bridge between an earlier Phase 1 study using API-in-capsule and IR tablet formulations of XEN901 and upcoming efficacy studies in SCN8A-DEE.