Objective:

To report the pharmacokinetics (PK) of cenobamate single- and multiple-dose regimens in the adolescent subgroup of patients (12 to <18 years old) from the open-label clinical studies (Study C039 [NCT04903314] and Study C040 [NCT05067634]) in pediatric patients (2 to <18 years old) with focal seizures.

Background:

Cenobamate is an antiseizure medication approved in the United States (XCOPRI®) for the treatment of focal seizures in adults.

Design/Methods:

Pediatric and adolescent PK data from studies C039 and C040, as well as data from healthy adults in bioavailability study C037, were incorporated into a previous population PK (PopPK) model of adult patients with focal seizures to determine the appropriate cenobamate dosing regimen (ie, body weight-based or flat-fixed) in adolescent patients. Dosing regimens were simulated assuming a 10-week up-titration period and maintenance dosing of 10 weeks. Steady-state exposures (AUC at steady-state) were simulated at the end of each target dose level in the 2-8 mg/kg (ie, 100-400 mg, adult equivalent) once-daily range.

Results:

Cenobamate PK was adequately described by a two-compartment model with first-order absorption and first-order elimination. The simulations indicated that the mean (90% prediction interval or PI) AUCs at steady state in adolescents on a cenobamate weight-based dose of 4 mg/kg once-daily (510 [251, 883] µg•h/mL) or flat dose of 200 mg once-daily (546 [260, 973] µg•h/mL) were comparable to the mean (90% PI) AUC at steady state in adults on a flat (ie, modal) dose of 200 mg once-daily (434 [207, 777] µg•h/mL). Exposures at all respective target doses (ie, mg/kg body weight-based or mg flat-fixed in adolescents vs flat-fixed in adults) were comparable.

Conclusions:

Cenobamate exposures in adolescent patients from the flat (mg) once-daily target doses of 100-400 mg were similar to those in adult subjects at the same respective approved cenobamate adult doses.