Abstracts

To compare the long-term efficacy and safety of oxcarbazepine monotherapy with phenytoin monotherapy in the open-label comparative follow-up phases of two multicenter, randomized, double-blind, controlled trials (Bill PA et al, 1997;27:195-204; Guerreiro et al, 1997;27:205-213).
Two 56-week double-blind, randomized studies compared oxcarbazepine monotherapy with phenytoin monotherapy in adults ([ge]16 years of age, Study 1) and children (5-17 years of age, Study 2) with newly diagnosed generalized tonic-clonic seizures or partial seizures. Patients who completed the Double-blind Phases were allowed to enter the Open-label Follow-up (OF) Phase of the respective study and continued on their original randomized treatment for another year. Pooled efficacy analysis, presented as Kaplan-Meier plots, included patients with seizure dairy data during the OF. Trends in the mean weekly seizure rate over time, using the log (weekly seizure rate + 0.001), and trends in total daily dose were studied over the additional 12 month period. Safety and tolerability were assessed based on reported adverse events and discontinuations.
Of total of 473 patients treated during the Double-blind Phases, 286 entered the OF phases (155 oxcarbazepine, 131 phenytoin). Seizure diary data was available for 187 of these patients (101 oxcarbazepine: Study 1 n=84 and Study 2 n=17; and, 86 phenytoin: Study 1 n=72 and Study 2 n=14). The median oxcarbazepine dose during OF was 900 mg/day (range: 300 to 2250 mg/day) for a median duration of 52 weeks. The median phenytoin dose was 300 mg/day (range: 100 to 500 mg/day) for a median duration of 50 weeks. Five (1.7%) patients discontinued due to adverse events (1 phenytoin) or lack of therapeutic control (3 oxcarbazepine, 1 phenytoin). The estimated seizure free rate over the 1 year OF was 67.2% (+/- 6.1%) for oxcarbazepine and 62.2% (+/- 6.9%) for phenytoin. This difference was not statistically significant. Kaplan Meier plots will be presented. The geometric mean weekly seizure rate for both groups was about 0.0012 seizures per week, which was constant over the 52 weeks of the OF for both groups. The most common adverse events ([gt]10%) during OF were: headache (oxcarbazepine 36.8%, phenytoin 31.3%), viral infection (oxcarbazepine 18.7%, phenytoin 22.9%), and gum hyperplasia (oxcarbazepine 3.9%, phenytoin 20.6%).
During this 1-year OF, seizure control with oxcarbazepine monotherapy in newly diagnosed patients with partial seizures was maintained over long-term treatment with a more favorable tolerability profile compared with phenytoin.
[Supported by: Novartis Pharma]