Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures
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Open Access
- 2 June 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 94 (22), e2311-e2322
- https://doi.org/10.1212/wnl.0000000000009530
Abstract
Objective To 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. Methods In 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. Results Two 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%). Conclusion Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated. ClinicalTrials.gov identifier NCT01397968. Classification of evidence This study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.Keywords
This publication has 35 references indexed in Scilit:
- Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089)Neurology, 2019
- Effects of cenobamate (YKP3089), a newly developed anti-epileptic drug, on voltage-gated sodium channels in rat hippocampal CA3 neuronsEuropean Journal of Pharmacology, 2019
- Active Epilepsy and Seizure Control in Adults — United States, 2013 and 2015Morbidity and Mortality Weekly Report (MMWR), 2018
- Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic DrugsJAMA Neurology, 2018
- ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and TerminologyEpilepsia, 2017
- Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and TerminologyEpilepsia, 2017
- Progress report on new antiepileptic drugs: A summary of the Eleventh Eilat Conference (EILAT XI)Epilepsy Research, 2013
- Patterns of treatment response in newly diagnosed epilepsyNeurology, 2012
- Add-on treatment with pregabalin for partial seizures with or without generalisation: Pooled data analysis of four randomised placebo-controlled trialsSeizure, 2009
- Early Identification of Refractory EpilepsyThe New England Journal of Medicine, 2000