Pharmacokinetics of XEN496, a Novel Pediatric Formulation of Ezogabine, Under Fed and Fasted Conditions: A Phase 1 Trial.

INTRODUCTION: XEN496 is a novel, granular, immediate-release formulation of ezogabine intended for pediatric use. The objective of this study was to assess the effect of food on the pharmacokinetics (PK) of XEN496 and its N-acetyl metabolite (NAMR) in healthy volunteers. METHODS: Twenty-four adult subjects were enrolled in this phase 1, single center, open-label, randomized, single-dose, two-way crossover study. Subjects received 400 mg XEN496 as an oral suspension in both fed and fasted states separated by a 6-day washout period. Serial blood samples were collected up to 48 h post-administration. PK parameters evaluated included maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration (Tmax), and area under the concentration-time curve (AUC(0-t) and AUCinf). Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. RESULTS: For XEN496, median Tmax was 3 and 2 h in the fed and fasted states, respectively. AUC parameters in the fed and fasted states were equivalent, whereas food decreased Cmax of XEN496 by 32% compared to the fasted state. The ratio of geometric means [90% CI] for Cmax was 72% [64-82%]. For NAMR, food delayed Tmax by 1 h, while Cmax and AUC parameters were equivalent in the fed and fasted states. The safety profile of XEN496 in this study appeared comparable to that previously reported for ezogabine tablets. CONCLUSION: The biopharmaceutical performance of XEN496 in this study was as expected for an immediate-release, granular dosage formulation, and generally comparable to that reported for ezogabine tablets. Future studies are needed to characterize the efficacy, safety, and PK of XEN496 in a pediatric population.