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

Abstract

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 (C_max), time of maximum observed plasma concentration (T_max), and area under the concentration-time curve (AUC_(0-t) and AUC_inf). Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring.

Results: For XEN496, median T_max 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 C_max of XEN496 by 32% compared to the fasted state. The ratio of geometric means [90% CI] for C_max was 72% [64-82%]. For NAMR, food delayed T_max by 1 h, while C_max 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.

Keywords: Ezogabine; Pharmacokinetics; Phase 1; XEN496.