Cenobamate Adverse Events by Time of Onset and Dose from Two Randomized Clinical Studies in Patients with Uncontrolled Focal Seizures
Abstract number :
1.322
Submission category :
7. Antiepileptic Drugs / 7D. Drug Side Effects
Year :
2019
Submission ID :
2421317
Source :
www.aesnet.org
Presentation date :
12/7/2019 6:00:00 PM
Published date :
Nov 25, 2019, 12:14 PM
Authors :
Louis Ferrari, SK Life science; William E. Rosenfeld, Comprehensive Epilepsy Care Center; Marc Kamin, SK Life Science, Inc.
Rationale: Results from two multicenter, placebo-controlled studies (YKP3089C013 [C013] and YKP3089C017 [C017]) showed that adjunctive treatment with cenobamate (CNB) 100, 200, and 400 mg/day (once daily) significantly decreased focal seizure frequency. The most common treatment-emergent adverse events (TEAEs) in both studies were CNS-related. Each study had a 6-week (wk) titration phase leading into a maintenance phase of 6 (C013) or 12 (C017) wks. In C013, patients were titrated up every other week, whereas patients in C017 were titrated up weekly. In this report, the number of TEAEs leading to discontinuation and serious TEAEs from both studies were assessed by time of onset and actual dose received. Methods: Adults with poorly controlled focal seizures who had >=3 seizures per month (C013) or >=8 seizures per 8 wks (C017) despite treatment with stable doses of 1-3 AEDs were enrolled. In C013, patients were randomized to placebo (PBO) or CNB 200 mg/day. During titration in C013, patients received 50 mg/day for 2 wks, 100 mg/day for 2 wks, and 150 mg/day for 2 wks before reaching 200 mg target dose. In C017, patients were randomized to PBO or 100, 200, or 400 mg/day CNB. During titration in C017, patients received increasing doses to reach their target dose: 50 mg/day for 1 wk, then 100 mg/day for 1 wk, then 150 mg/day for 1 wk, then 200 mg/for 1 wk, then 300 mg/day for 1 wk, then 400 mg/day for 1 wk. Dose of concomitant AEDS could not be adjusted in either study. Results: In C013, 4.4% (5/113) of CNB patients had TEAEs that led to discontinuation at doses of 50 mg (n=4) and 100 mg (n=1). In 4/5 of the patients, the TEAEs occurred during the 6-wk titration period and in 1 patient, the TEAE occurred during wk 11. In C017, 14.6% (48/329) of CNB patients had TEAEs that led to discontinuation, and these events were reported by patients at doses of 100 mg (31.3% [15/48]), 150 mg (6.3% [3/48]), 200 mg (27.1% [13/48]), 300 mg (8.3% [4/48]), and 400 mg (27.1% [13/48]). In the majority of patients, the TEAEs leading to discontinuation occurred during titration (70.8% [34/48]). In C013, two serious TEAEs were reported with CNB (drug hypersensitivity and urinary tract infection). Both occurred during the 6-wk titration phase, one at a dose of 50 mg and another at 150 mg. In C017, serious TEAEs were reported in 22 patients with CNB. Seizure and suicidal ideation were the only serious TEAEs that occurred in >=1% of patients. In 59.0% (13/22), the serious TEAEs occurred during the 6-wk titration phase. Serious TEAEs were reported at doses of 100 mg (54.5% [12/22]), 200 mg (13.6% [3/22]), 300 mg (4.5% [1/22]), and by 400 mg (27.3% [6/22]). Conclusions: Most TEAEs leading to treatment discontinuations and serious TEAEs occurred during titration and, based on the dose at which they occurred, generally were earlier in the titration phase. TEAEs leading to discontinuation and serious TEAEs occurred less frequently in C013 compared to C017, suggesting titrating CNB at 2-wk intervals may improve tolerability. Funding: SK Life Science, Inc.
Antiepileptic Drugs