PMID- 35705501
OWN - NLM
STAT- MEDLINE
DCOM- 20231220
LR  - 20231224
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 99
IP  - 10
DP  - 2022 Sep 5
TI  - Long-term Efficacy and Safety From an Open-Label Extension of Adjunctive 
      Cenobamate in Patients With Uncontrolled Focal Seizures.
PG  - e989-e998
LID - 10.1212/WNL.0000000000200792 [doi]
AB  - BACKGROUND AND OBJECTIVES: To evaluate long-term efficacy (percent seizure 
      frequency reduction and responder rates), safety, and tolerability of adjunctive 
      cenobamate (CNB) in an open-label extension (OLE) of the randomized, 
      double-blind, placebo-controlled study. METHODS: Patients (aged 18-70 years) with 
      uncontrolled focal seizures despite treatment with 1-3 antiseizure medications 
      who completed the 18-week double-blind study (n = 360) could enter the OLE, where 
      they underwent a 2-week blinded conversion to CNB (target dose, 300 mg/d; 
      min/max, 50/400 mg/d). RESULTS: Three hundred fifty-five patients were included 
      in the OLE safety population (265 originally randomized to CNB, 90 originally 
      randomized to placebo), and 354 were included in the OLE modified intent-to-treat 
      population. As of July 2019, 58.9% of patients (209/355) were continuing CNB 
      treatment and 141 had discontinued, including 16.6% (59/355) because of lack of 
      efficacy, 8.7% (31/355) because of withdrawal by patient, and 7.6% (27/355) 
      because of adverse events. The median (range) duration of OLE exposure was 53.9 
      (1.1-68.7) months. Retention rates at 12, 24, 36, and 48 months were 83%, 71%, 
      65%, and 62%, respectively. Median percent seizure frequency reduction over 
      baseline increased with each 6-month OLE interval, up to 76.1% at months 43-48. 
      Among observed patients, 16.4% (36/220) achieved 100% and 39.1% (86/220) achieved 
      >/=90% seizure reduction during >36-48 months. Among the initial OLE modified 
      intent-to-treat population, 10.2% of patients (36/354) achieved 100% and 24.3% 
      (86/354) achieved >/=90% seizure reduction during >36-48 months. Similar to the 
      double-blind study, adverse events (AEs) included dizziness, somnolence, fatigue, 
      and headache. Serious AEs occurred in 20.3% of patients (72/355). DISCUSSION: 
      Long-term efficacy, including 100% and >/=90% seizure reduction, was sustained 
      during 48 months of CNB treatment, with 71% retention at 24 months. No new safety 
      issues were identified. These results confirm the findings of the double-blind 
      study and support the potential long-term clinical benefit of CNB. CLASSIFICATION 
      OF EVIDENCE: This study provides Class IV evidence that oral CNB 50-400 mg/d is 
      effective as an adjunctive treatment for the long-term management of patients 
      with uncontrolled focal seizures previously treated with 1-3 ASMs. TRIAL 
      REGISTRATION INFORMATION: ClinicalTrials.gov NCT01866111 
      (clinicaltrials.gov/ct2/show/results/NCT01866111).
CI  - Copyright (c) 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Klein, Pavel
AU  - Klein P
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain. kleinp@epilepsydc.com.
FAU - Aboumatar, Sami
AU  - Aboumatar S
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Brandt, Christian
AU  - Brandt C
AUID- ORCID: 0000-0001-8666-1640
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Dong, Fang
AU  - Dong F
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Krauss, Gregory L
AU  - Krauss GL
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Mizne, Sarah
AU  - Mizne S
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Sanchez-Alvarez, Juan Carlos
AU  - Sanchez-Alvarez JC
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Steinhoff, Bernhard J
AU  - Steinhoff BJ
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
FAU - Villanueva, Vicente
AU  - Villanueva V
AD  - From the Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Austin 
      Epilepsy Care Center (S.A.), Austin, TX; Bethel Epilepsy Centre (C.B.), Mara 
      Hospital, Bielefeld, Germany; SK Life Science, Inc. (F.D.), Paramus, NJ; Johns 
      Hopkins University School of Medicine (G.L.K.), Baltimore, MD; MedVal Scientific 
      Information Services (S.M.), Princeton, NJ; Unidad de Epilepsia (J.C.S.-A.), 
      Hospital Vithas la Salud, Granada, Spain; Kork Epilepsy Center (B.J.S.), 
      Kehl-Kork, Germany; Department of Neurology and Neurophysiology (B.J.S.), 
      University of Freiburg, Germany; and Refractory Epilepsy Unit (V.V.), Hospital 
      Universitari i Politecnic La Fe, Valencia, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT01866111
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220905
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - P85X70RZWS (Cenobamate)
RN  - 0 (Anticonvulsants)
SB  - IM
MH  - Humans
MH  - *Anticonvulsants/adverse effects
MH  - Treatment Outcome
MH  - Drug Therapy, Combination
MH  - *Seizures/drug therapy/chemically induced
MH  - Double-Blind Method
PMC - PMC9519254
EDAT- 2022/06/16 06:00
MHDA- 2023/12/20 06:42
PMCR- 2022/09/18
CRDT- 2022/06/15 22:13
PHST- 2021/06/30 00:00 [received]
PHST- 2022/04/11 00:00 [accepted]
PHST- 2023/12/20 06:42 [medline]
PHST- 2022/06/16 06:00 [pubmed]
PHST- 2022/06/15 22:13 [entrez]
PHST- 2022/09/18 00:00 [pmc-release]
AID - WNL.0000000000200792 [pii]
AID - WNL-2022-200774 [pii]
AID - 10.1212/WNL.0000000000200792 [doi]
PST - epublish
SO  - Neurology. 2022 Sep 5;99(10):e989-e998. doi: 10.1212/WNL.0000000000200792.