TY - JOUR
T1 - Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures
AU - Chung, Steve S.
AU - French, Jacqueline A.
AU - Kowalski, Jacek
AU - Krauss, Gregory L.
AU - Lee, Sang Kun
AU - MacIejowski, MacIej
AU - Rosenfeld, William E.
AU - Sperling, Michael R.
AU - Mizne, Sarah
AU - Kamin, Marc
N1 - Funding Information:
The authors thank Don Fallon, ELS, of MedVal Scientific Information Services, LLC (Princeton, NJ) for providing medical editing assistance, which was funded by SK Life Science, Inc. This manuscript was prepared according to the International Society for Medical Publication Professionals' “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.”
Funding Information:
S.S. Chung is a consultant for Adamas, Eisai, SK Life Science, Inc, and UCB; is a speaker for Eisai, Greenwich Biosciences, Sunovion, and UCB; and received grant support from Engage, SK Life Science, Inc, and UCB. J.A. French receives New York University (NYU) salary support from the Epilepsy Foundation and for consulting work and/or attending Scientific Advisory boards on behalf of the Epilepsy Study Consortium for Acadia, Adamas, Addex, Aeonian, Alexza, Anavex, Axcella, Axovant, Biogen, BioMotiv/Koutif, Blackfynn, Bloom Science, Bridge Valley Ventures, Cavion, Cerebral Therapeutics, Cerevel, Clinilabs, Concert Pharmaceuticals, Covance, Crossject, CuroNZ, Eisai, Empatica, Engage, Epitel, GW Pharma, Idorsia, Impax, Ionis, J&J Pharmaceuticals, Marinus, MonoSol Rx, Neurelis, Novartis, Otsuka, Ovid, Pfizer, Pfizer-Neusentis, Praxis, Redpin, Sage, Sancilio, Shire, SK Life Science, Inc, SpringWorks, Stoke, Sunovion, Supernus, Takeda, UCB, Ultragenyx, Upsher-Smith, Vyera, West Therapeutic Development, Xenon, Xeris, Zogenix, and Zynerba. J. French has also received research grants from Biogen, Cavion, Engage, Neurelis, Ovid, SK Life Science, Inc, UCB, and Zogenix, as well as grants from the Epilepsy Research Foundation, Epilepsy Study Consortium, and National Institute of Neurological Disorders and Stroke. She is on the editorial board of Lancet Neurology and Neurology Today. She is scientific officer for the Epilepsy Foundation, for which NYU receives salary support. She has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Adamas, Axovant, Biogen, Blackfynn, CuroNZ, Eisai, Engage, Idorsia, Neurelis, Novartis, Otsuka, Ovid, Pfizer, Redpin, Sage, SK Life Science, Inc, Sunovion, Takeda, UCB, Ultragenyx, and Zynerba. J. Kowalski has received research support from SK Life Science, Inc. G.L. Krauss is a consultant/advisor for Eisai, Otsuka, and Shire and received research support from SK Life Science, Inc, UCB, and Biogen. S.K. Lee is a consultant/advisor for Eisai, UCB, and SK Life Science, Inc. M. Maciejowski has served as a speaker for Biogen, Merck, Novartis, and Roche and received grant support from Roche. W.E. Rosenfeld is a consultant/advisor for SK Life Science, Inc and Eisai; has received honoraria for speaking from Eisai, Greenwich Biosciences (GW Pharmaceuticals), Sunovion, and UCB; and received grant/research support from Greenwich Biosciences, Marinus, Medtronic, Neurelis, Ovid, SK Life Science, Inc, Takeda, UCB, and Upsher-Smith. M.R. Sperling is a consultant/advisor for Medtronic (fee to institution) and consultant to NeurologyLive and received research support (to institution) from Eisai, Engage, Medtronic, Neurelis, Pfizer, SK Life Science, Inc, Takeda, UCB, and Xenon. S. Mizne is an employee of MedVal Scientific Information Services, which was contracted by SK Life Science, Inc for medical writing services. M. Kamin is an employee of SK Life Science, Inc. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2020/6/2
Y1 - 2020/6/2
N2 - ObjectiveTo evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs.MethodsIn this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment.ResultsTwo hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0-237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%).ConclusionAdjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated.ClinicalTrials.gov identifierNCT01397968.Classification of evidenceThis study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.
AB - ObjectiveTo evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs.MethodsIn this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment.ResultsTwo hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0-237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%).ConclusionAdjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated.ClinicalTrials.gov identifierNCT01397968.Classification of evidenceThis study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.
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U2 - 10.1212/WNL.0000000000009530
DO - 10.1212/WNL.0000000000009530
M3 - Article
C2 - 32409485
AN - SCOPUS:85085905523
SN - 0028-3878
VL - 94
SP - E2311-E2322
JO - Neurology
JF - Neurology
IS - 22
ER -