Abstract Details

Title Cenobamate in Adolescent Patients With Focal Epilepsy: A Phase 1 Pharmacokinetic Study to Determine an Appropriate Dosing Regimen to Optimize Safety, Tolerability, and Efficacy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-003

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.

Authors/Disclosures
Vijaykumar Vashi (SK Life Science Inc) PRESENTER	Vijaykumar Vashi has nothing to disclose.
Gopal Krishna, PhD	Dr. Krishna has received personal compensation for serving as an employee of SK Life Sciences .
Fredrik Jonsson, PhD	The institution of Dr. Jonsson has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Company qPharmetra. LLC.
Sunita N. Misra, MD (SK Life Science)	Dr. Misra has received personal compensation for serving as an employee of SK Life Science, Inc. An immediate family member of Dr. Misra has received personal compensation for serving as an employee of Neurocrine Biosciences.

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