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

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.