Epilepsia · 2026
Systematic statistical analysis of change in SEIzure interVAL with diazepam nasal spray supports this novel clinical endpoint for immediate-use seizure medication.
Клиническое исследование III фазыСтатьяНазвание и аннотация: Перевод в очереди
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Kerr Wesley T, McFarlane Katherine N, Ngo Leock Y, Carrazana Enrique, Rabinowicz Adrian L
Аннотация
OBJECTIVE: Appropriate endpoints for daily antiseizure medications may differ from those for intermittent, immediate-use seizure medications (ISMs). The observed interval between seizure clusters over time (SEIzure interVAL [SEIVAL]) has been proposed as a novel effectiveness endpoint for ISMs. SEIVAL was initially identified pragmatically. This post hoc analysis evaluated how the study timeline and participant characteristics could impact the measurement of SEIVAL using data from an open-label study of intermittent treatment with diazepam nasal spray.
METHODS: This analysis includes data from a long-term, phase 3 safety study of diazepam nasal spray, which enrolled patients aged 6-65 years with epilepsy and seizure clusters (NCT02721069). Study timeline and participant characteristic choices were evaluated systematically to determine the impact on effect size, and thereby statistical power, using data regarding individual treated seizure clusters. In this strategy, the date of the first treated seizure cluster constituted day 1 of the baseline period; consecutive 70-day periods were used for analysis. The change in SEIVAL for each patient was calculated using each measured SEIVAL for that patient in the primary outcome period (days 71-140) minus that patient's mean SEIVAL in the baseline period (days 1-70) with mixed effects linear regression.
RESULTS: Mean SEIVAL increased from 13 days at baseline (days 1-70) to 24 days in the primary outcome period (days 71-140, p < .0001). SEIVAL lengthening was seen in adults, adolescents (ages 6-17 years), and children (ages 6-12 years), with further lengthening past 140 days in adolescents and children. SEIVAL lengthened more in participants with <1 SEIVAL per 2 weeks at baseline than higher SEIVAL frequency.
SIGNIFICANCE: This systematically planned analysis expands on and reinforces the previous pragmatic analysis that introduced the SEIVAL metric. The present analysis provides a novel framework for future studies of intermittently administered ISMs to treat seizure clusters such as diazepam nasal spray.
METHODS: This analysis includes data from a long-term, phase 3 safety study of diazepam nasal spray, which enrolled patients aged 6-65 years with epilepsy and seizure clusters (NCT02721069). Study timeline and participant characteristic choices were evaluated systematically to determine the impact on effect size, and thereby statistical power, using data regarding individual treated seizure clusters. In this strategy, the date of the first treated seizure cluster constituted day 1 of the baseline period; consecutive 70-day periods were used for analysis. The change in SEIVAL for each patient was calculated using each measured SEIVAL for that patient in the primary outcome period (days 71-140) minus that patient's mean SEIVAL in the baseline period (days 1-70) with mixed effects linear regression.
RESULTS: Mean SEIVAL increased from 13 days at baseline (days 1-70) to 24 days in the primary outcome period (days 71-140, p < .0001). SEIVAL lengthening was seen in adults, adolescents (ages 6-17 years), and children (ages 6-12 years), with further lengthening past 140 days in adolescents and children. SEIVAL lengthened more in participants with <1 SEIVAL per 2 weeks at baseline than higher SEIVAL frequency.
SIGNIFICANCE: This systematically planned analysis expands on and reinforces the previous pragmatic analysis that introduced the SEIVAL metric. The present analysis provides a novel framework for future studies of intermittently administered ISMs to treat seizure clusters such as diazepam nasal spray.