Abstracts

Rationale: Results from a 12-week, double-blind (DB), placebo-controlled YKP3089C013 (C013) study demonstrated significant reductions in median percentage seizure frequency/month with adjunctive cenobamate (CNB) 200 mg/day. The most common treatment-emergent adverse events (TEAEs) with CNB during DB treatment were somnolence, dizziness, and headache. Here we report long-term safety outcomes from the ongoing open-label extension (OLE) of C013. Methods: In C013, adults 18-65 years old with uncontrolled focal seizures who had >=3 seizures per month despite treatment with stable doses of 1-3 antiepileptic drugs (AEDs) were randomized to receive placebo (PBO) or CNB 200 mg/day. The study had a 6-week titration phase and a 6-week maintenance phase. Patients who completed the DB study were eligible to enroll in an OLE. At the end of DB treatment, patients were either tapered off study drug before transitioning to open-label treatment or were allowed to directly convert to open-label CNB without being tapered off, if medically warranted (following protocol amendment). The maximum allowed daily dose of CNB during the OLE was 400 mg. Results: Of the 201 patients who completed the C013 DB study, 43 were from study sites that did not participate in the OLE. Of the remaining 158 patients, 149 entered the OLE, including 76 patients originally randomized to CNB (CNB/CNB) and 73 patients originally randomized to PBO who transitioned to CNB (PBO/CNB). Demographics were similar between groups (median number of baseline AEDs 2 each). The median duration of CNB exposure was 60.6 months (range, 0.3-79.4 months). The median modal daily CNB dose was 200 mg (range, 50-400 mg). As of April 2018, 86 patients (57.7%) remained in the OLE, including 52.6% (40/76) of CNB/CNB patients and 63.0% (46/73) of PBO/CNB patients. Reasons for discontinuation overall were withdrawal by patient in 18.8% (n=15 CNB/CNB; n=13 PBO/CNB), adverse events in 9.4% (n=9 CNB/CNB; n=5 PBO/CNB), other in 8.7% (n=7 CNB/CNB; n=6 PBO/CNB), lost to follow-up in 2.7% (n=2 CNB/CNB; n=2 PBO/CNB), and pregnancy in <1% (n=1 CNB/CNB). Treatment-emergent adverse events (TEAEs) were reported in 88.6% (n=132) of patients (safety population, N=149). Dizziness, headache, and somnolence were the most frequently reported TEAEs (Table). Serious TEAEs occurred in 22.8% (n=34) of patients. Serious TEAEs occurring in >1% of patients were seizure (n=5) and pneumonia, sepsis, and osteoarthritis (n=2, each). TEAEs leading to discontinuation were reported in 9.4% (n=14) of patients overall, including 9 CNB/CNB patients and 5 PBO/CNB patients.  Conclusions: Adjunctive CNB was generally well tolerated with long-term treatment (up to 79 months), with 58% of patients ongoing at the time of this analysis. Most TEAEs were central nervous system-related consistent with the DB study. Funding: SK Life Science, Inc.