Abstract Details

Title Cenobamate Adverse Events by Time of Onset and Dose From Two Randomized Clinical Studies in Patients With Uncontrolled Focal Seizures

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P11 - Poster Session 11 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-009

Objective Assess treatment-emergent adverse events (TEAEs) leading to discontinuation and serious TEAEs by time of onset and dose from 2 multicenter, placebo-controlled studies of cenobamate (YKP3089C013 [C013] and YKP3089C017 [C017]).

Background Each study had a 6-week titration phase leading into a maintenance phase of 6 (C013) or 12 (C017) weeks. Cenobamate was titrated up every other week (C013) or weekly (C017).

Design/Methods Adults with uncontrolled focal seizures having ≥3 seizures/month (C013) or ≥8 seizures/8 weeks (C017) despite treatment with stable doses of 1-3 AEDs were enrolled. In C013, patients were randomized to placebo or cenobamate 200mg/day. In C017, patients were randomized to placebo or 100, 200, or 400mg/day cenobamate. Doses of concomitant AEDs could not be adjusted in either study.

Results In C013, 4.4% (5/113) of cenobamate patients had TEAEs that led to discontinuation at doses of 50 (n=4) and 100mg (n=1). In 4/5 of the patients, the TEAEs occurred during the 6-week titration phase. In C017, 14.6% (48/329) of cenobamate patients had TEAEs that led to discontinuation at doses of 100 (31.3% [15/48]), 150 (6.3% [3/48]), 200 (27.1% [13/48]), 300 (8.3% [4/48]), and 400mg (27.1% [13/48]). In most patients, the TEAEs leading to discontinuation occurred during titration (77.1% [37/48]). In C013, 2 serious TEAEs occurring during titration at doses of 50 and 150mg were reported with cenobamate. In C017, serious TEAEs were reported in 22 patients with cenobamate. In 59.0% (13/22) of these patients, serious TEAEs occurred during titration and were reported at doses of 100 (54.5% [12/22]), 200 (13.6% [3/22]), 300 (4.5% [1/22]), and 400mg (27.3% [6/22]).

Conclusions Most TEAEs leading to treatment discontinuations and serious TEAEs occurred during the titration phase. TEAEs leading to discontinuation and serious TEAEs occurred less frequently in C013 vs C017, suggesting that titrating cenobamate at 2-week intervals may improve tolerability.

Authors/Disclosures
Louis Ferrari (SK Lifescience) PRESENTER	Louis Ferrari has received personal compensation for serving as an employee of SK Life science.
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 $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science.
Marc Kamin, MD	Dr. Kamin has received personal compensation for serving as an employee of SK LIFE SCIENCE INC.

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