To generate pharmacokinetic (PK) data to guide the dosing regimen for an upcoming pediatric efficacy trial and conduct a retrospective comparative PK and safety assessment to bridge between XEN496 and previously developed IR tablet used in adults (Potiga®/Trobalt^TM, GlaxoSmithKline).

Xenon is developing XEN496, a pediatric immediate-release formulation of Ezogabine (a Kv7.2/7.3 potassium channel modulator), for the treatment of KNCQ2-related developmental and epileptic encephalopathy (KCNQ2-DEE).  Ezogabine was previously approved as an IR tablet by the US Food and Drug Administration (FDA) for treatment of adult focal onset seizures and used of label for KCNQ2-DEE; however, it was withdrawn from the global market in July 2017 for commercial reasons.  Xenon Pharmaceuticals has received orphan drug designation from the FDA for XEN496 as a treatment of KCNQ2-DEE and received supporting feedback to study XEN496 in infants and children up to 4 years old.

In this open label, randomized, single dose, two-treatment, two-period, two-sequence, crossover study, 24 subjects receive a single dose of XEN496 (equivalent to 400 mg of Ezogabine) under fasted or fed conditions for two 48-hour in-unit treatment periods, each separated by at least 6 days.

A 400 mg dose was used in this study. The dose selection was based on PK and safety data available for Potiga® (Product Monograph) and limited data available from off-label use of Potiga® in pediatric and adolescent populations (Millichap et al. and Tompson et al., respectively).  In addition, this strength was the reference standard recommended by the FDA to be used as the appropriate comparator for the purposes of bioequivalence testing for Potiga®.  This study is ongoing and the results will be available for poster presentation.

The results from this study are expected to provide guidance and facilitate dose selection for a planned XEN496 pediatric study in KCNQ2-DEE.