Epilepsia · 2026
Increased interval between seizure clusters across time in pediatric patients treated with the immediate-use seizure medication diazepam nasal spray.
Клиническое исследование I фазыКлиническое исследование II фазыСтатьяНазвание и аннотация: Перевод в очереди
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Wheless James W, Segal Eric, Peters Jurriaan M, Wolf Steven M, Bougher Genei, Davis Charles, Ngo Leock Y, Carrazana Enrique, Rabinowicz Adrian L
Аннотация
OBJECTIVE: Seizure clusters, intermittent increases in seizure activity that differ from a patient's usual seizure pattern, may occur despite treatment with a daily anti-seizure medication. Benzodiazepine-containing immediate-use seizure medications (ISMs; also called rescue therapies) are the cornerstone of treatment for seizure clusters. Diazepam nasal spray is approved by the U.S. Food and Drug Administration to treat seizure clusters in patients with epilepsy ≥2 years of age. A prior long-term safety study of diazepam nasal spray showed an increased inter-seizure cluster interval (SEIzure interVAL [SEIVAL]) in days across a year in patients 6 to 65 years of age. The current analysis focused on changes in SEIVAL over time in a separate study in children with epilepsy 2 to 5 years of age.
METHODS: Patients with epilepsy 2 to 5 years of age were enrolled in an open-label, Phase 1/2a trial of diazepam nasal spray that included a single-dose pharmacokinetics period, 180-day safety period, and optional extension period. Doses of 5, 10, or 15 mg were administered based on weight (0.5 mg/kg). A post hoc analysis evaluated SEIVAL for consecutive 90-day periods overall and in a consistent cohort of patients with persistent use and SEIVALs in each period.
RESULTS: Among enrolled patients (n = 36), 22 (61.1%) had ≥1 SEIVAL, with a total of 315 SEIVALs recorded. Mean SEIVAL (±SD) doubled from 25.2 (±21.3) days in Period 1 (n = 20) to 51.9 (±72.4) days in Period 3 (n = 8). In the consistent cohort (n = 7), mean SEIVAL increased from 22.1 (±12.7) days in Period 1 to 27.7 (±25.4) days in Period 3.
SIGNIFICANCE: These results corroborate those of the earlier post hoc analysis of data from patients 6 to 65 years of age who received diazepam nasal spray for seizure clusters. These findings suggest a beneficial long-term treatment effect of diazepam nasal spray beyond acute use as an ISM.
METHODS: Patients with epilepsy 2 to 5 years of age were enrolled in an open-label, Phase 1/2a trial of diazepam nasal spray that included a single-dose pharmacokinetics period, 180-day safety period, and optional extension period. Doses of 5, 10, or 15 mg were administered based on weight (0.5 mg/kg). A post hoc analysis evaluated SEIVAL for consecutive 90-day periods overall and in a consistent cohort of patients with persistent use and SEIVALs in each period.
RESULTS: Among enrolled patients (n = 36), 22 (61.1%) had ≥1 SEIVAL, with a total of 315 SEIVALs recorded. Mean SEIVAL (±SD) doubled from 25.2 (±21.3) days in Period 1 (n = 20) to 51.9 (±72.4) days in Period 3 (n = 8). In the consistent cohort (n = 7), mean SEIVAL increased from 22.1 (±12.7) days in Period 1 to 27.7 (±25.4) days in Period 3.
SIGNIFICANCE: These results corroborate those of the earlier post hoc analysis of data from patients 6 to 65 years of age who received diazepam nasal spray for seizure clusters. These findings suggest a beneficial long-term treatment effect of diazepam nasal spray beyond acute use as an ISM.