CARISBAMATE AS ADJUNCTIVE TREATMENT OF PARTIAL ONSET SEIZURES IN ADULTS IN TWO INTERNATIONAL, RANDOMIZED, PLACEBO-CONTROLLED TRIALS
Abstract number :
1.243
Submission category :
7. Antiepileptic Drugs
Year :
2008
Submission ID :
8785
Source :
www.aesnet.org
Presentation date :
12/5/2008 12:00:00 AM
Published date :
Dec 4, 2008, 06:00 AM
Authors :
Michael Sperling, A. Greenspan, Joyce Cramer, Patrick Kwan, R. Kalviainen, Jonathan Halford, Jennifer Schmitt, M. Haas, Eric Yuen and Gerad Novak
Rationale: The efficacy and safety of carisbamate as adjunctive treatment in partial onset seizures (POS) was previously demonstrated in a phase 2 trial. The trials reported here assessed the efficacy, safety, and tolerability of carisbamate (200 mg/day or 400 mg/day) as adjunctive treatment, including the lower end of the dose range previously tested. Methods: Two identically designed randomized, phase 3, placebo-controlled, global studies were conducted September 2006 - October 2007. Adults with an established diagnosis of uncontrolled POS for ≧1 yr were eligible. Patients remained on stable doses of prescribed AEDs (≤2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to receive carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, without titration, in 2 equally divided doses, for a 12-week double-blind (DB) phase. Efficacy endpoints were median percent reduction in seizure frequency in the DB phase compared to the prospective baseline phase and the proportion of patients with ≥50% reduction in POS frequency (responder rate) during the DB phase. Safety assessments included adverse events (AEs), laboratory tests, and ECGs. Results: Patient characteristics were similar across both studies and treatment arms: mean ages, 35 yrs (range 16-75; study 1 [S1]) and 36 yrs (range 16-74; study 2 [S2]), approximately 50% men. Most patients were either white (61% S1; 53 % S2) or Asian (36% S1; 46% S2). Most completed the DB phase: n=527/ 565 (93%; S1) and 528/562 (94%; S2). The most frequently used concomitant AEDs were carbamazepine, 43% (S1), 48% (S2) and valproate, 35% (S1), 28% (S2). Treatment with carisbamate 400 mg resulted in improvement in both efficacy measures compared with placebo only in S1, not S2. Carisbamate 200 mg did not differ from placebo in either study (Table 1). Concomitant use of uridine diphosphate glucuronosyltransferase inducing AEDs lowered plasma levels of carisbamate by up to 40% (S2) and 44% (S1). The most common adverse events (≧5% in any group) with an incidence exceeding placebo were dizziness and somnolence. The rate of treatment-emergent adverse events resulting in discontinuation from carisbamate was 3% in each study. Of 752 carisbamate-treated patients, 2 (0.3%) patients had clinically significant elevations of alanine aminotransferase, including one with acute hepatitis B infection. Conclusions: Carisbamate 400mg/day was effective in one of these studies. These results support previous data that more than 200 mg/day of carisbamate is required for efficacy. Carisbamate was well tolerated with minimal CNS-related adverse events and a low discontinuation rate.
Antiepileptic Drugs