Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized, placebo-controlled trials.
OBJECTIVE
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.
Sperling
Michael R
MR
Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Michael.Sperling@jefferson.edu
Greenspan
Andrew
A
Cramer
Joyce A
JA
Kwan
Patrick
P
Kälviäinen
Reetta
R
Halford
Jonathan J
JJ
Schmitt
Jennifer
J
Yuen
Eric
E
Cook
Thomas
T
Haas
Magali
M
Novak
Gerald
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome
D000927:Anticonvulsants; D002219:Carbamates; D010919:Placebos; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase