Shorter Time to Treatment with Diazepam Nasal Spray Is Associated with Faster Seizure Termination: A Subpopulation Analysis
Danielle Becker1, Randa Jarrar2, John Stern3, Adrian Rabinowicz4, Enrique Carrazana4
1University of Pennsylvania, 2Phoenix Children’s Hospital, 3Geffen School of Medicine, 4Neurelis, Inc.
Objective:
To investigate temporal patterns of seizure clusters treated with diazepam nasal spray (Valtoco®) in adult and pediatric subpopulations and in patients with ≥20 recorded seizure clusters.
Background:
Diazepam nasal spray is approved for the acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. An earlier study-wide analysis found that shorter time from seizure-cluster start to treatment with diazepam nasal spray was associated with shorter seizure duration.
Design/Methods:
Seizure-cluster data from a phase 3 safety study of diazepam nasal spray were analyzed post hoc based on the timing of seizure start, administration of treatment, and seizure cessation. Observations recording seizure duration >24 hours, negative duration, and invalid dose date/time values were excluded from the analysis. Medians were calculated.
Results:
Of 4466 observations (163 patients), 3225 were included; 1567 for adults (18–65 years) and 1658 for pediatric patients (6–17 years). For 2169 seizures treated in <5 minutes, median times from dose to seizure termination were 2 and 3 minutes, respectively. In comparison, for 727 seizures treated in 5–15 minutes, times from dosing to termination were 10 and 5 minutes, while for 329 seizures treated in ≥15 minutes, times from dosing to termination were 20 and 8 minutes. In 61 adult and pediatric patients with ≥20 observations (2484 total observations), of those treated in <5 minutes, time from dosing to termination was 3 minutes, while for those treated in ≥5 minutes, time from dosing to termination was 11 minutes. Overall, safety was similar to diazepam rectal gel.
Conclusions:
For subpopulations based on age or treatment usage, shorter time (<5 min) to treatment with diazepam nasal spray was associated with shorter time to seizure cluster termination in this single-arm study. These findings warrant further exploration of their clinical implications and generalizability.