Abstracts

Rationale: Carisbamate is a novel neuromodulatory agent in development for the adjunctive treatment of epilepsy. This study assessed the efficacy and tolerability of adjunctive treatment with 4 dosages of carisbamate in patients with refractory partial-onset seizures (POS). Methods: In this multicenter, randomized, double-blind placebo-controlled trial, subjects (n=537) aged 17-69 were randomly assigned to treatment with placebo or 1 of 4 dosages of carisbamate (100, 300, 800, and 1600mg/d in 2 divided doses), added to 1-3 concomitant antiepileptic drugs (AEDs). A prospective 8-wk baseline period was followed by 16-wk of double-blind treatment, including a 4-wk titration. The primary efficacy variable was percent reduction of POS from baseline. An intention to treat analysis was conducted using a Wilcoxon rank sum test controlled for pooled centers. Results: Adult subjects (mean age 37.1 ±11.58 years old) had epilepsy for a median of 22 years with a median of 6 prior AED exposures; 35.8% were receiving 3 concomitant AEDs. All treatment groups were similar in POS frequency at baseline (median 10.5/28 days, range 3-445). The median percent reduction from baseline in POS versus placebo was 6.2%; 100mg, 15.4% (p=0.073 vs. placebo); 300mg, 24.0% (p<0.001); 800mg, 20.9% (p=0.006); and 1,600mg, 28.6% (p<0.001). Most common treatment-emergent adverse events (AEs) were headache, dizziness, and somnolence, generally mild to moderate in severity and more common at 1,600mg. Fewer subjects discontinued due to AE in the 100mg (5%) and 300mg (6%) groups than for placebo (8%), while 12% discontinued from the 800mg and 19% from the 1,600mg groups. Serious AEs occurred at a rate of 6% for placebo in comparison to 3-4% for any carisbamate dose. Conclusions: Dosages of 300, 800 and 1,600mg/d were of comparable significant efficacy in reducing seizure frequency in this highly refractory population. The 100, 300, and 800mg/d dosages were well tolerated. A daily dosage of 300mg provided the optimal balance of efficacy and tolerability.