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Abstract Details

A Review of the Pharmacokinetic Properties of Cenobamate (YKP3089), a Novel Antiepileptic Drug for the Treatment of Uncontrolled Focal Seizures in Adults
Epilepsy/Clinical Neurophysiology (EEG)
P11 - Poster Session 11 (8:00 AM-9:00 AM)
12-008
Review results from multiple studies evaluating effects of age, renal impairment (RI), hepatic impairment (HI), food, coadministration of other antiepileptics, and cytochrome P450 (CYP) probes on pharmacokinetics (PK) and safety of cenobamate.
Cenobamate is an antiepileptic in development for treatment of uncontrolled focal seizures.
Age effect study included healthy young (18-45 y/o; n=12) and elderly (≥65 y/o; n=12) subjects. RI study included mild RI (n=8), moderate RI (n=6), and normal (n=8) subjects. HI study included mild HI, moderate HI, and normal subjects (N=24). All others included healthy subjects (food effect: N=34; drug-drug interaction [DDI]: N=80; CYP probe: N=24). Absence of effect was concluded if 90% CIs of geometric mean ratios for Cmax and AUC were within reference range (0.80-1.25) for test vs reference groups.
In elderly vs young subjects, no meaningful difference was observed in Cmax or AUC. Cenobamate Cmax was within reference range, and AUC values were ~1.5-fold higher in mild and moderate RI vs normal subjects. Mild or moderate HI subjects had ~2-fold greater AUC and limited Cmax effects vs normal subjects. Cenobamate AUC values were similar in fed vs fasted conditions with ~1-h delay in tmax with food. Coadministration of cenobamate with phenobarbital, carbamazepine, or divalproex showed limited effects on cenobamate exposure. Phenytoin significantly decreased cenobamate Cmax and AUC. Cenobamate coadministration increased Cmax and AUC for phenobarbital and phenytoin and decreased carbamazepine exposure. For CYP probes, cenobamate 200 mg/day induced CYP2B6 (bupropion) and CYP3A (midazolam) and inhibited CYP2C19 (omeprazole) with high variability. CYP3A induction by cenobamate was less marked at 100 mg/day. No significant effects were observed on CYP2C9 (warfarin) activity. Cenobamate was generally safe and well-tolerated in all studies.
These studies provide an understanding of the disposition of cenobamate in special populations and in combination with other drugs. Results will be used to support dosing recommendations.
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.
Laurent Vernillet No disclosure on file