TY - JOUR
T1 - Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures
T2 - Open-label extension of a randomized clinical study
AU - French, Jacqueline A.
AU - Chung, Steve S.
AU - Krauss, Gregory L.
AU - Lee, Sang Kun
AU - Maciejowski, Maciej
AU - Rosenfeld, William E.
AU - Sperling, Michael R.
AU - Kamin, Marc
N1 - Funding Information:
J.A.F.: Salary support to New York University: Epilepsy Foundation; consultant/advisor (on behalf of the Epilepsy Study Consortium): Adamas, Aeonian/Aeovian, Anavex, Arkin Holdings, Arvelle, Athenen Therapeutics/Carnot Pharma, Baergic, Biogen, BioXcel, Cavion, Cerebral, Cerevel, Crossject, CuroNZ, Eisai, Eliem, Encoded, Engage, Engrail, Epiminder, Equilibre, Fortress, Greenwich, GW Pharma, Janssen, Knopp, Lundbeck, Marinus, Mend Neuroscience, Merck, NeuCyte, Neurocrine, Otsuka, Ovid, Passage, Praxis, Redpin, Sage, SK Life Science, Sofinnova, Stoke, Supernus, Synergia Medical, Takeda, UCB Pharma, West Therapeutic Development, Xenon, Xeris, Zogenix, Zynerba; research support: Epilepsy Research Foundation, Epilepsy Study Consortium (funded by Andrews Foundation, Eisai, Engage, Lundbeck, Pfizer, SK Life Science, Sunovion, UCB Pharma, Vogelstein Foundation), Epilepsy Study Consortium/Epilepsy Foundation (funded by Engage, Neurelis, SK Life Science, UCB Pharma), GW/One8 Foundation/FACES, National Institute of Neurological Disorders and Stroke; editorial board: , ; travel reimbursement: Arvelle, Biogen, Cerevel, Engage, Epilepsy Study Consortium, Epilepsy Foundation, Lundbeck, NeuCyte, Otsuka, Sage, UCB Pharma, Xenon, Zogenix. S.S.C.: Consultant/advisor: Adamas, Eisai, SK Life Science, UCB Pharma; speaker: Eisai, Greenwich Biosciences, Sunovion, UCB Pharma; research support: Engage, SK Life Science, UCB Pharma. G.L.K.: Consultant/advisor: Adamas, Eisai, Otsuka, Shire; research support: Biogen, SK Life Science, UCB Pharma, Upsher‐Smith. S.K.L.: Consultant/advisor: Eisai, SK Life Science, UCB Pharma. M.M.: Speaker: Biogen, Merck, Novartis, Roche; research support: Roche. W.E.R.: Consultant/advisor: SK Life Science; speaker: Eisai, Greenwich Biosciences (GW Pharmaceuticals), SK Life Science, Sunovion, UCB Pharma; research support: Greenwich Biosciences, Marinus, Medtronic, Neurelis, Ovid, SK Life Science, Takeda, UCB Pharma, Upsher‐Smith. M.R.S.: Consultant/advisor: Medtronic; speaker: Eisai, International Medical Press, Medscape, NeurologyLive, Projects in Knowledge; research support: Cavion, Cerevel, Eisai, Engage, Medtronic, Neurelis, SK Life Science, Takeda, UCB Pharma, Xenon. M.K.: Employee, SK Life Science. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Lancet Neurology Neurology Today
Funding Information:
This study was funded by SK Life Science. The authors thank Lynanne McGuire, PhD, and Don Fallon, ELS, of MedVal Scientific Information Services for medical writing and editorial assistance, which were funded by SK Life Science. This article was prepared according to the International Society for Medical Publication Professionals’ Good Publication Practice for Communicating Company‐Sponsored Medical Research: GPP3.
Funding Information:
This study was funded by SK Life Science. The authors thank Lynanne McGuire, PhD, and Don Fallon, ELS, of MedVal Scientific Information Services for medical writing and editorial assistance, which were funded by SK Life Science. This article was prepared according to the International Society for Medical Publication Professionals’ Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.
Publisher Copyright:
© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
PY - 2021/9
Y1 - 2021/9
N2 - Objective: This study was undertaken to examine long-term (up to 7.8 years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open-label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968). Methods: Patients who completed the 12-week, multicenter, multinational, double-blind, randomized, placebo-controlled C013 study, which examined adjunctive cenobamate treatment of adults with uncontrolled focal seizures, were eligible to enroll in the OLE. During the OLE, dose adjustments of cenobamate and concomitant ASMs were allowed. Safety assessments included frequency of treatment-emergent adverse events (TEAEs) and serious TEAEs, TEAE severity, and TEAEs leading to discontinuation. Probability of patient continuation in the OLE was examined using a Kaplan–Meier analysis. Results: One hundred forty-nine patients entered the OLE (median duration of cenobamate treatment = 6.25 years). As of the data cutoff, 57% of patients (85/149) remained in the OLE (median treatment duration = 6.8 years, range = 6.4–7.8 years). The median modal daily cenobamate dose was 200 mg (range = 50–400 mg). The probability of treatment continuation at 1–6 years of cenobamate treatment was 73%, 67%, 63%, 61%, 60%, and 59%, respectively. Among patients who continued at 1 year (n = 107), the probability of continuing at Years 2–5 was 92%, 87%, 83%, and 82%. The most common discontinuation reasons were patient withdrawal (19.5%, 29/149), adverse event (10.1%, 15/149), and lack of efficacy (5.4%, 8/149). TEAEs leading to discontinuation in 1% or more of patients were fatigue (1.3%, 2/149), ataxia (1.3%, 2/149), and memory impairment or amnesia (1.3%, 2/149). Dizziness (32.9%, 49/149), headache (26.8%, 40/149), and somnolence (21.5%, 32/149) were the most frequently reported TEAEs and were primarily mild or moderate in severity. Significance: Long-term retention in the C013 OLE study demonstrated sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8 years in adults with treatment-resistant focal seizures taking one to three ASMs.
AB - Objective: This study was undertaken to examine long-term (up to 7.8 years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open-label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968). Methods: Patients who completed the 12-week, multicenter, multinational, double-blind, randomized, placebo-controlled C013 study, which examined adjunctive cenobamate treatment of adults with uncontrolled focal seizures, were eligible to enroll in the OLE. During the OLE, dose adjustments of cenobamate and concomitant ASMs were allowed. Safety assessments included frequency of treatment-emergent adverse events (TEAEs) and serious TEAEs, TEAE severity, and TEAEs leading to discontinuation. Probability of patient continuation in the OLE was examined using a Kaplan–Meier analysis. Results: One hundred forty-nine patients entered the OLE (median duration of cenobamate treatment = 6.25 years). As of the data cutoff, 57% of patients (85/149) remained in the OLE (median treatment duration = 6.8 years, range = 6.4–7.8 years). The median modal daily cenobamate dose was 200 mg (range = 50–400 mg). The probability of treatment continuation at 1–6 years of cenobamate treatment was 73%, 67%, 63%, 61%, 60%, and 59%, respectively. Among patients who continued at 1 year (n = 107), the probability of continuing at Years 2–5 was 92%, 87%, 83%, and 82%. The most common discontinuation reasons were patient withdrawal (19.5%, 29/149), adverse event (10.1%, 15/149), and lack of efficacy (5.4%, 8/149). TEAEs leading to discontinuation in 1% or more of patients were fatigue (1.3%, 2/149), ataxia (1.3%, 2/149), and memory impairment or amnesia (1.3%, 2/149). Dizziness (32.9%, 49/149), headache (26.8%, 40/149), and somnolence (21.5%, 32/149) were the most frequently reported TEAEs and were primarily mild or moderate in severity. Significance: Long-term retention in the C013 OLE study demonstrated sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8 years in adults with treatment-resistant focal seizures taking one to three ASMs.
KW - epilepsy
KW - focal seizures
KW - long-term
KW - retention
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85109693426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85109693426&partnerID=8YFLogxK
U2 - 10.1111/epi.17007
DO - 10.1111/epi.17007
M3 - Article
C2 - 34254673
AN - SCOPUS:85109693426
SN - 0013-9580
VL - 62
SP - 2142
EP - 2150
JO - Epilepsia
JF - Epilepsia
IS - 9
ER -