Oxcarbazepine adjunctive therapy for partial seizures in Japanese pediatric patients: a randomized double-blind placebo-controlled study and open-label extension study

Purpose: To assess the efficacy, safety, and pharmacokinetics of oxcarbazepine (OXC) as an adjunctive therapy in Japanese pediatric patients with inadequately controlled partial seizures.Methods: We conducted a double-blind, randomized, multi-center, placebo-controlled study (the core study) and its open-label extension study. In the core study, the primary efficacy end point was percent change from baseline in seizure frequency per 28 days at week 8.Results: In the core study, a total of 99 patients were randomized. The median percent change in seizure frequency per 28 days from baseline was -15.30% in patients taking OXC and +2.44% in those taking placebo but the unadjusted difference was not significantly different between two groups (p = 0.0585). However, preplanned sensitive analysis that adjusted the primary efficacy end point by baseline seizure frequency per 28 days (p = 0.0492) and analyses of secondary efficacy end points (responder rate and Clinical Global Impression of Change, p = 0.0157 and 0.0007, respectively) demonstrated significant differences between OXC and placebo. In the extension study, the decrease of seizure frequency in OXC–OXC group (patients randomized to OXC in core study and continued taking OXC in extension study) was maintained, In the switching group (Placebo–OXC: patients randomized to placebo in core study and took OXC in extension study) seizure frequency decreased at a similar level as OXC–OXC group. Common drug-related adverse events observed in the studies were nervous system disorders (somnolence, dizziness), skin disorders (rash, drug eruption), and gastrointestinal disorders (vomiting, nausea). Two cases of hypersensitivity requiring hospitalization were reported, but no serious skin disorders such as Stevens-Johnson syndrome and toxic epidermal necrolysis.Conclusion: The results showed that adjunctive OXC treatment was effective and well tolerated in Japanese pediatric patients with inadequately controlled partial seizures.