title: Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome.
abstract: OBJECTIVE
  To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as adjunctive therapy for Lennox-Gastaut syndrome (LGS).
  
  
  METHODS
  Patients aged 2-60 years were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day. Study consisted of 4-week baseline, 3-week titration, and 12-week maintenance phases, followed by a 2- or 3-week taper or continuation in an open-label extension. Primary endpoint was percentage decrease in mean weekly drop seizure rates during maintenance vs baseline phases for modified intention-to-treat (mITT) population. Secondary outcomes included other seizure types, responder rates, and physicians' and caregivers' global assessments.
  
  
  RESULTS
  A total of 305 patients were screened, 238 were randomized, and 217 composed the mITT population. Of patients enrolled after a protocol amendment, 125/157 (79.6%) completed. Average weekly drop seizure rates decreased 12.1% for placebo vs 41.2% (p = 0.0120), 49.4% (p = 0.0015), and 68.3% (p < 0.0001) for the clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Responder rates (≥50%) were 31.6% (placebo) vs 43.4% (p = 0.3383), 58.6% (p = 0.0159), and 77.6% (p < 0.0001) for clobazam 0.25-, 0.5-, and 1.0-mg/kg/day groups. Physicians' and caregivers' assessments indicated clobazam significantly improved symptoms. Somnolence, pyrexia, upper respiratory infections, and lethargy were the most frequent adverse events reported for clobazam.
  
  
  CONCLUSIONS
  Clobazam significantly decreased weekly drop seizure rates in LGS. No new safety signals were identified.
  
  
  METHODS
  This study provides Class II evidence that clobazam as adjunctive therapy is efficacious, in a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients with LGS over 12 weeks.
authors.affiliation: St. Joseph’s Hospital Medical Center and Barrow Neurological Institute, Phoenix, AZ, USA. y-ng@ouhsc.edu
authors.forename: Y T
authors.initials: YT
authors.lastname: Ng
authors.forename: J A
authors.initials: JA
authors.lastname: Conry
authors.forename: R
authors.initials: R
authors.lastname: Drummond
authors.forename: J
authors.initials: J
authors.lastname: Stolle
authors.forename: M A
authors.initials: MA
authors.lastname: Weinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D001315:Australia; D001569:Benzodiazepines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy*; D007391:International Cooperation; D065768:Lennox Gastaut Syndrome; D008297:Male; D008875:Middle Aged; D013036:Spasms, Infantile / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam