Abstract Details

Title The Pharmacokinetics of Cenobamate in Special Populations

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-034

Objective Three clinical studies were conducted with the objective of assessing differences in the pharmacokinetics (PK) of cenobamate in special populations, including elderly, renally impaired, and hepatically impaired subjects compared to healthy adult subjects.

Background Cenobamate is a novel compound developed for partial-onset seizures. A ¹⁴C-labeled cenobamate study in healthy volunteers showed that cenobamate is extensively metabolized and renally excreted with approximately 87.5% of the dose being recovered in urine (6.4% as unchanged drug). Understanding PK differences in renal impairment (RI), hepatic impairment (HI), and elderly populations is important for dosing cenobamate appropriately in these special populations.

Design/Methods The HI, RI, and elderly studies were conducted in 24, 22, and 26 subjects, respectively. Each subject received a single 200-mg oral dose of cenobamate. PK samples were collected up to 456 hours post-dose. Geometric least-squared mean (GLSM) PK parameters (C_max or AUC) of subjects with mild or moderate HI (Child-Pugh), mild or moderate RI (Cockcroft-Gault), and elderly (age >65 years) subjects were compared to the GLSM PK parameters in healthy adult subjects with normal renal or hepatic functions, or younger age (18-45 years old), respectively.

Results Subjects with mild (n=8) or moderate (n=6) RI showed an approximate 1.5-fold increase in AUC. Changes in C_max were deemed insignificant. Subjects with mild (n=8) or moderate (n=8) HI showed a 2-fold increase in AUC with limited effect on C_max. No clinically meaningful differences in cenobamate PK were observed in elderly subjects (n=12). A single 200 mg dose of cenobamate was safe and well tolerated across all studies.

Conclusions The Increase in total body exposure (AUC) of cenobamate in the RI and HI studies may need to be accounted for when properly dosing patients with cenobamate. No dose adjustment of cenobamate is needed in elderly patients. No significant safety or tolerability concerns were identified across these 3 studies.

Authors/Disclosures
Stephen Greene (SK Life Science Inc) PRESENTER	Stephen Greene has received personal compensation for serving as an employee of SK Life Science, Inc.
	No disclosure on file
Caroline Streicher (Axsome Therapeutics)	Caroline Streicher has received personal compensation for serving as an employee of Axsome Therapeutics. Caroline Streicher has stock in Axsome Therapeutics.
Laurent Vernillet	No disclosure on file

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