To evaluate the impact of phenytoin CYP induction on the pharmacokinetics of XEN901 and potential pharmacodynamic interactions between XEN901 and phenytoin.

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). In early clinical development, XEN901 will be used as adjunctive therapy with other antiepileptic drugs (AEDs), many of which are potent CYP inducers (e.g., carbamazepine and phenytoin). Since phenytoin is a more potent CYP inducer than carbamazepine and is one of the two inducers of the CYP3A4 enzyme recommended for clinical drug-drug interaction studies by the Food and Drug Administration, phenytoin was selected for the study presented here.

To date, 18 subjects have completed the Day 1 dosing with 100 mg of XEN901, with no clinically significant electrocardiogram or laboratory findings. The safety data indicated that all reported AEs were mild and unrelated to XEN901, with the exception of one moderate related AE (vomiting). There have been no serious adverse events. Final results will be available for presentation.