Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized, placebo-controlled trials

Authors


Address correspondence to Michael R. Sperling, M.D., Baldwin Keyes Professor of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, 900 Walnut St., Suite 200 Philadelphia, PA 19107, U.S.A. E-mail: Michael.Sperling@jefferson.edu

Summary

Purpose: 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 ≥1 year. Therapy-refractory epilepsy patients (≥16 years) remained on stable doses of prescribed antiepileptic drugs (≤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 ≥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 (≥5% in any group), those with an incidence exceeding placebo (≥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.

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