Randomized, controlled, dose-ranging trial of carisbamate for partial-onset seizures.
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.
Faught
E
E
University of Alabama at Birmingham Epilepsy Center, Civitan International Research Center 312, 1719 6th Ave. South, Birmingham, AL 35294-0021, USA. faught@uab.edu
Holmes
G L
GL
Rosenfeld
W E
WE
Novak
G
G
Neto
W
W
Greenspan
A
A
Schmitt
J
J
Yuen
E
E
Reines
S
S
Haas
M
M
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
D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; D000410:Alanine Transaminase