Abstract Details

Title Cognitive and Psychiatric Adverse Events During Adjunctive Cenobamate Treatment in Phase 2 and Phase 3 Clinical Studies

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 10-005

Background Epilepsy treatment with antiseizure medications (ASMs) can be limited by cognitive and behavioral TEAEs that negatively affect patient quality of life.

Objective To evaluate cognitive and psychiatric treatment-emergent adverse events (TEAEs) during adjunctive cenobamate treatment.

Design/Methods This post-hoc analysis of adjunctive cenobamate clinical trials included adult patients with uncontrolled focal seizures taking 1-3 concomitant ASMs in a pooled analysis of two phase 2 randomized, double-blind, placebo-controlled trials (12-week YKP3089C013 [C013]/18-week YKP3089C017 [C017]; n=442 cenobamate, n=216 placebo) and in a pooled analysis of the long-term C013/C017 open-label extensions (OLEs) and the long-term maintenance phase of the phase 3 open-label safety study (YKP3089C021 [C021]). Total C013OLE/C017OLE/C021 pooled n=1844 cenobamate-treated. Cognitive TEAE areas included disturbance in attention, language, and memory. Psychiatric TEAE areas included aggression, anger, hostility, and irritability; mood changes, anxiety, and depression; confusional state; psychosis; and suicidality. The percentage of patients who had cognitive/psychiatric TEAEs are reported for the pooled C013/C017 double-blind studies. Pooled C013OLE/C017OLE/C021 TEAEs were analyzed using exposure-adjusted event rates through 5 years of cenobamate treatment.

Results In the pooled double-blind studies, memory impairment was the most frequent cognitive TEAE (1.8% of cenobamate patients [8/442] vs 0.5% of placebo patients [1/216]). Confusional state was the most frequent psychiatric TEAE (2.5% [11/442] cenobamate vs no placebo patients). Most cognitive and psychiatric TEAEs were mild/moderate. In the pooled C013OLE/C017OLE/C021 studies, the total cognitive TEAEs occurrence per patient-year was 0.0704 (Year 1), 0.0364 (Year 2), 0.0687 (Year 3), 0.0098 (Year 4), and 0.0857 (Year 5). The total psychiatric TEAEs occurrence per patient-year was 0.1963 (Year 1), 0.1233 (Year 2), 0.1418 (Year 3), 0.0391 (Year 4), and 0.1500 (Year 5).

Conclusions There was a low occurrence of cognitive and psychiatric TEAEs over a treatment duration of up to 5 years in adjunctive cenobamate clinical trials.

Authors/Disclosures
Gregory Krauss, MD (Johns Hopkins University) PRESENTER	Dr. Krauss has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvelle. Dr. Krauss has received stock or an ownership interest from EpiWatch.
Steve Chung, MD, FAAN (Banner University Medical Center)	The institution of Dr. Chung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ucb pharma. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SK Life sciences. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for ucb. Dr. Chung has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for SK Life sciences. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for sunovion.
Louis Ferrari	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 $100,000-$499,999 for serving on a Speakers Bureau for SK Life Science.