Abstracts

To examine the efficacy and safety of oxcarbazepine (OXC) as monotherapy and adjunctive therapy in adolescents (12-17 years) with newly diagnosed or uncontrolled partial seizures. Data collected from 10 multicenter, double-blind, randomized clinical trials (5 monotherapy, 3 substitution to monotherapy, 2 adjunctive) designed to evaluate the efficacy and safety of OXC were included in the analysis. New onset patients were enrolled in 5 monotherapy studies: 2 placebo-controlled (18-36 mg/kg/day; 1200 mg/day) and 3 active-controlled (1 study: 2400 mg/day OXC, 2400 mg/day valproate; 2 studies: 2400 mg OXC, 800 mg/day phenytoin). Refractory patients were enrolled in 5 adjunctive/substitution studies: 2 placebo-controlled, add-on parallel-group (study 1: 600, 1200, and 2400 mg/day; study 2: up to 46 mg/kg/day), one parallel-group (2700 mg/day BID vs TID), and 2 dose-controlled (300 and 2400 mg/day). The duration of the studies ranged from 12 weeks to 56 weeks (monotherapy) and 16 to 56 weeks (adjunctive/substitution). Data for all OXC-treated patients in both types of studies were combined and analyzed separately. Response rates for patients becoming seizure free and experiencing a 75% or 50% reduction in seizure frequency throughout the double-blind period were assessed for the intent-to-treat population. Adverse events (AEs) were tabulated. A total of 72 and 96 adolescents received OXC as monotherapy or adjunctive/substitution therapy, respectively, with a mean age of 15 years for both types of studies. In the monotherapy studies, 39 (54%) patients completed their respective study: 6 (8%) discontinued due to AEs, 1 (1%) for lack of efficacy, and 26 (36%) for other reasons. In the adjunctive/substitution studies, 78 (81%) patients completed their respective study: 15 (16%) discontinued due to AEs, 1 (1%) for lack of efficacy, and 2 (2%) for other reasons. For the monotherapy studies, 53% of OXC-treated patients were seizure free with 86% and 88% of patients experiencing at least a 75% and 50% response, respectively. In the adjunctive/substitution studies, 4% of OXC-treated patients were seizure free with 25% and 41% of patients experiencing at least a 75% and 50% response, respectively. The most common ([ge]20%) AEs in the monotherapy studies were headache, dizziness, somnolence, viral infection and nausea. For the adjunctive/substitution studies, the most common ([ge]20%) AEs were vomiting, somnolence, dizziness and headache. The clinical utility of OXC in adolescents (12-17 years) with newly diagnosed partial seizures has been demonstrated by the large proportion of patients who were seizure free following monotherapy. Relatively high seizure response rates were also observed in adolescents with uncontrolled seizures after treatment with OXC as adjunctive/substitution therapy. Overall, OXC was safe and well tolerated. (Supported by Novartis Pharmaceuticals.)