Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized, placebo-controlled trials

Epilepsia. 2010 Mar;51(3):333-43. doi: 10.1111/j.1528-1167.2009.02318.x. Epub 2009 Oct 27.


Purpose: To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial-onset seizures (POS).

Methods: Two identical, randomized, placebo-controlled, double-blind studies were conducted in adults with POS uncontrolled for >or=1 year. Therapy-refractory epilepsy patients (>or=16 years) remained on stable doses of prescribed antiepileptic drugs (<or=2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12-week double-blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with >or=50% reduction in POS frequency) during the double-blind phase compared with the prospective baseline phase.

Results: Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16-75 years) and 36 years (study 2, range 16-74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p < 0.01) in both efficacy measures compared with placebo in study 1 but not in study 2. Carisbamate 200 mg/day did not differ statistically from placebo in either study. Among the most common treatment-emergent adverse events (>or=5% in any group), those with an incidence exceeding placebo (>or=3%) were dizziness (400 mg/day group) and somnolence.

Conclusions: Carisbamate 400 mg/day was effective in patients with refractory partial-onset seizures in one of these global studies. More than 200 mg/day of carisbamate is required for efficacy. Carisbamate was well-tolerated in both studies.

Trial registration: NCT00425282 NCT00433667.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use*
  • Carbamates / adverse effects
  • Carbamates / pharmacokinetics
  • Carbamates / therapeutic use*
  • Dizziness / chemically induced
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Epilepsies, Partial / drug therapy*
  • Epilepsies, Partial / metabolism
  • Female
  • Glucuronosyltransferase / metabolism
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Sleep / drug effects
  • Treatment Outcome


  • Anticonvulsants
  • Carbamates
  • Placebos
  • S-2-O-carbamoyl-1-o-chlorophenyl-ethanol
  • UDP-glucuronosyltransferase, UGT1A6
  • Glucuronosyltransferase

Associated data