A randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of adjunctive carisbamate treatment in patients with partial-onset seizures.

Abstract

PURPOSE:

To assess the efficacy, safety, and tolerability of adjunctive carisbamate treatment at 800 mg/day and 1,200 mg/day in patients with partial-onset seizures (POS).

METHODS:

Patients ≥ 16 years of age with an established diagnosis of POS for ≥ 1 year and uncontrolled on one to three antiepileptic drugs were enrolled. Eligible patients remained on stable doses of prescribed antiepileptic drugs for an 8-week pretreatment baseline phase and were then randomized (1:1:1) to receive carisbamate (800 mg/day or 1,200 mg/day), or placebo, for a 14-week double-blind phase. Primary efficacy endpoints were percentage reduction in POS frequency and responder rate (patients with ≥ 50% reduction in POS frequency) during the double-blind versus baseline phase.

KEY FINDINGS:

Five hundred forty-seven patients were randomized; 540 composed the intent-to-treat (ITT) analysis. Four hundred thirty-four patients (79%) completed the study. The median percent reduction from baseline to treatment phase in POS frequency was: 21% (placebo); 30% (carisbamate 800 mg); 36% (carisbamate 1,200 mg), and 32% (combined carisbamate doses). The combined carisbamate dose group was not significantly different from placebo for the median percent reduction of POS frequency (p = 0.20) or responder rate (p = 0.18). Therefore, the difference from placebo for the individual carisbamate dose groups was also considered nonsignificant, based on a prespecified step-down analysis. Dizziness was the most common treatment-emergent adverse event, with a higher incidence (≥ 5% difference) in the combined carisbamate group (31%) than placebo (9%); the incidence was higher with carisbamate 1,200 mg (32%, n = 58) than with carisbamate 800 mg (30%, n = 53).

SIGNIFICANCE:

Adjunctive carisbamate therapy in patients with POS did not demonstrate efficacy across the dose range assessed versus placebo. No new safety findings were observed.

• Authors: Jonathan J Halford, Elinor Ben-Menachem, Patrick Kwan, Seth Ness, Jennifer Schmitt, Mariëlle Eerdekens, Gerald Novak
• Journal: Epilepsia (Epilepsia) Vol. 52 Issue 4 Pg. 816-25 (Apr 2011) ISSN: 1528-1167 [Electronic] United States
• PMID: 21320109 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Chemical References

• Anticonvulsants
• Carbamates
• S-2-O-carbamoyl-1-o-chlorophenyl-ethanol

Topics

• Adult
• Anticonvulsants (administration & dosage, adverse effects)
• Carbamates (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination (methods)
• Epilepsies, Partial (diagnosis, drug therapy)
• Female
• Humans
• Male
• Middle Aged
• Outcome Assessment, Health Care (methods)