Abstract Details

Title The Pharmacokinetics of Cenobamate When Used as Monotherapy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P4 - Poster Session 4 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-009

Background

To support monotherapy use, the drug dosages used as monotherapy should result in exposures that are similar to those demonstrated to be safe and effective when the drug is used as adjunctive therapy for the treatment of focal seizures.

Objective A population pharmacokinetic (PK) model-based analysis of pooled data from clinical studies conducted in healthy subjects, special populations, and patients with focal seizures was used to evaluate expected exposure to cenobamate when used as monotherapy compared to adjunctive therapy.

Design/Methods Repeated daily maintenance dosing of cenobamate at 100, 200, and 400 mg was used to simulate plasma exposure, expressed as area under the plasma concentration vs time curve (AUC). The following antiseizure medications (ASMs) were tested as covariates for statistically significant effects on the apparent clearance (CL/F) of cenobamate based on their use in clinical studies of patients with focal seizures: carbamazepine, clobazam, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and valproate. ASMs with a statistically significant effect on the CL/F of cenobamate were used as the adjunctive therapy in the comparison with monotherapy. Treatment equivalence was determined if the derived 90% confidence interval (CI) of the ratio of the AUC log under cenobamate monotherapy, divided by the simulated AUC log when given as adjunctive therapy, fell within 0.8-1.25 (ie, no effect).

Results Lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and valproate did not show any statistically significant effects on CL/F of cenobamate in the population PK model. Clobazam and carbamazepine showed statistically significant effects on CL/F; however, the derived 90% CIs of the monotherapy/adjunctive therapy ratios fell within the 0.8-1.25 limit. Therefore, plasma cenobamate exposures with adjunctive therapy were comparable to monotherapy.

Conclusions Based on these findings, cenobamate monotherapy should result in plasma exposures comparable to those that have been demonstrated to be safe and effective when used as adjunctive therapy for the treatment of focal seizures.

Authors/Disclosures
Vijaykumar Vashi (SK Life Science Inc) PRESENTER	No disclosure on file
William E. Rosenfeld, MD, FAAN (Comprehensive Epilepsy Care Center for Children and Adults)	The institution of Dr. Rosenfeld has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for SK Life Science. Dr. Rosenfeld has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for SK Life Science.
Louis Ferrari	Louis Ferrari has received personal compensation for serving as an employee of SK Life science.
Marc Kamin, MD	Dr. Kamin has received personal compensation for serving as an employee of SK LIFE SCIENCE INC.