title: Rufinamide as an adjunctive therapy for Lennox-Gastaut syndrome: a randomized double-blind placebo-controlled trial in Japan.
abstract: OBJECTIVE
  To evaluate the efficacy, safety, and pharmacokinetics of rufinamide as an adjunctive therapy for patients with Lennox-Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to rufinamide or placebo. The primary efficacy variable was the percent change in the tonic-atonic seizure frequency per 28 days.
  
  
  RESULTS
  Of the 59 patients, 29 were randomized to the rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the rufinamide group than in the placebo group; the median percent change in frequency of tonic-atonic seizures was -24.2% and -3.3%, respectively, (p=0.003) and that of total seizures was -32.9% and -3.1%, respectively (p<0.001). Subgroup analyses indicated that the efficacy of rufinamide was consistent independent of clinical background characteristics. The common treatment-related adverse events in the rufinamide group were decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%). Transient seizure aggravations were observed in 13 (22.0%) of the 59 patients, though a causal relationship with rufinamide was suspected in only one patient. All adverse events were mild to moderate in severity. The mean plasma concentration of rufinamide between 1 and 9 within 12h after administration was 17.2 μg/mL.
  
  
  CONCLUSIONS
  The present results showed a favorable risk-benefit profile for rufinamide as an adjunctive therapy for patients with LGS.
authors.affiliation: Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: ohtsuka@okayama-u.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohtsuka
authors.affiliation: Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Yoshinaga
authors.affiliation: Shirasaka Clinic, East Court 2nd Avenue 103, 1-14 Koyo-cho Naka, Higashinada-ku, Kobe 658-0032, Japan.
authors.forename: Yukiyoshi
authors.initials: Y
authors.lastname: Shirasaka
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka 420-8688, Japan.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Takayama
authors.affiliation: Japan/Asia Clinical Research Product Creation Unit, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takano
authors.affiliation: Department of Pediatrics, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima 730-8518, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Iyoda
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D065768:Lennox Gastaut Syndrome / Q000188:drug therapy*; D008297:Male; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide
keywords: Efficacy; Lennox–Gastaut syndrome; Pharmacokinetics; Randomized double-blind placebo-controlled trial; Rufinamide; Tolerability