title: Randomized, controlled, dose-ranging trial of carisbamate for partial-onset seizures.
abstract: OBJECTIVE
  To evaluate the efficacy, safety, and tolerability of carisbamate (CRS), an investigational drug, as adjunctive treatment for partial-onset seizures in adults.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, multicenter, dose-ranging study was conducted in 12 countries. Patients counted seizures during an 8-week baseline period, and then, if eligible, entered a double-blind phase consisting of a 4-week dose-titration period (target CRS doses: 100, 300, 800, or 1,600 mg/d or placebo in two divided doses) and a 12-week maintenance period. The primary efficacy variable was percent reduction in partial-onset seizure frequency during the double-blind phase compared with pretreatment baseline. Safety data and responder rates were also assessed.
  
  
  RESULTS
  Five hundred thirty-seven patients were randomized, and 82% completed the study. In the intent-to-treat population (n = 533), CRS at doses of > or =300 mg/d (p < or = 0.006) reduced the frequency of partial-onset seizures vs placebo: 6% (placebo) vs 24% (300 mg/d), 21% (800 mg/d), and 29% (1,600 mg/d) for CRS. Adverse events consisted primarily of CNS effects, and led to discontinuation of drug in 8% of the placebo group vs 5% (100 mg/d), 6% (300 mg/d), 12% (800 mg/d), and 19% (1,600 mg/d) of the CRS groups.
  
  
  CONCLUSIONS
  Carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures.
authors.affiliation: University of Alabama at Birmingham Epilepsy Center, Civitan International Research Center 312, 1719 6th Ave. South, Birmingham, AL 35294-0021, USA. faught@uab.edu
authors.forename: E
authors.initials: E
authors.lastname: Faught
authors.forename: G L
authors.initials: GL
authors.lastname: Holmes
authors.forename: W E
authors.initials: WE
authors.lastname: Rosenfeld
authors.forename: G
authors.initials: G
authors.lastname: Novak
authors.forename: W
authors.initials: W
authors.lastname: Neto
authors.forename: A
authors.initials: A
authors.lastname: Greenspan
authors.forename: J
authors.initials: J
authors.lastname: Schmitt
authors.forename: E
authors.initials: E
authors.lastname: Yuen
authors.forename: S
authors.initials: S
authors.lastname: Reines
authors.forename: M
authors.initials: M
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000927:Anticonvulsants / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002219:Carbamates / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; D000410:Alanine Transaminase