Drugs in R&D · 2012
Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain.
Клиническое исследованиеСтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Casas-Fernández Carlos, Martínez-Bermejo Antonio, Rufo-Campos Miguel, Smeyers-Durá Patricia, Herranz-Fernández José L, Ibáñez-Micó Salvador, Campistol-Plana Jaume, Alarcón-Martínez Helena, Campos-Castelló Jaime
Аннотация
BACKGROUND: The safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients.
OBJECTIVE: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. DesignMethods: The trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT®; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1-2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ≥1 other AED. Treatment response to lacosamide was determined by assessing the change in seizure frequency after 3 months of lacosamide therapy. Responders were defined as patients who achieved a seizure frequency reduction of >50%. Tolerability was assessed by the reporting of adverse effects, laboratory testing, and electroencephalography recordings.
RESULTS: Lacosamide was dosed at a mean of 6.80 ± 2.39 mg/kg/day. After 3 months of lacosamide therapy, 62.3% of patients achieved a >50% reduction in seizure frequency, with complete seizure suppression being reported in 13.8% of patients. Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events. In ten patients, instability, difficulty walking, an inability to relate to subjective elements, and blurred vision or dizziness were reported. A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation. The symptoms were markedly different in each patient, preventing determination of a causal factor(s).
CONCLUSIONS: The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy. Further evaluation in a randomized, controlled trial is needed to validate the efficacy in this population and to fully investigate the adverse effects described here. We recommend an initial dose of 1-2 mg/kg/day, uptitrated to 6-9 mg/kg/day over 4-6 weeks.
OBJECTIVE: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. DesignMethods: The trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT®; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1-2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ≥1 other AED. Treatment response to lacosamide was determined by assessing the change in seizure frequency after 3 months of lacosamide therapy. Responders were defined as patients who achieved a seizure frequency reduction of >50%. Tolerability was assessed by the reporting of adverse effects, laboratory testing, and electroencephalography recordings.
RESULTS: Lacosamide was dosed at a mean of 6.80 ± 2.39 mg/kg/day. After 3 months of lacosamide therapy, 62.3% of patients achieved a >50% reduction in seizure frequency, with complete seizure suppression being reported in 13.8% of patients. Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events. In ten patients, instability, difficulty walking, an inability to relate to subjective elements, and blurred vision or dizziness were reported. A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation. The symptoms were markedly different in each patient, preventing determination of a causal factor(s).
CONCLUSIONS: The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy. Further evaluation in a randomized, controlled trial is needed to validate the efficacy in this population and to fully investigate the adverse effects described here. We recommend an initial dose of 1-2 mg/kg/day, uptitrated to 6-9 mg/kg/day over 4-6 weeks.