Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures

• Published in: Neurology Vol. 94; no. 22; p. e2311
• Main Authors: Chung, Steve S, French, Jacqueline A, Kowalski, Jacek, Krauss, Gregory L, Lee, Sang Kun, Maciejowski, Maciej, Rosenfeld, William E, Sperling, Michael R, Mizne, Sarah, Kamin, Marc
• Format: Journal Article
• Language: English
• Published: United States 02.06.2020
• Subjects: Adolescent; Adult; Anticonvulsants - administration & dosage; Carbamates - administration & dosage; Chlorophenols - administration & dosage; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Seizures - diagnosis; Seizures - drug therapy; Seizures - physiopathology; Tetrazoles - administration & dosage; Young Adult
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000009530

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. 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. 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%; < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo ( < 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%). Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated. NCT01397968. This study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.