Faster Time to Treatment of Seizure Clusters With Diazepam Nasal Spray Is Associated With Faster Cessation of Clusters and a Similar Rate of Second Dose Usage
Sunita Misra1, Randa Jarrar2, John Stern3, Danielle Becker4, Adrian Rabinowicz1, Enrique Carrazana5
1Neurelis, Inc., San Diego, CA, 2Phoenix Children’s Hospital, Phoenix, AZ, 3Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 4Case Western Reserve University School of Medicine, Cleveland, OH, 5Neurelis, Inc., San Diego, CA and John A. Burns School of Medicine, University of Hawaii, Honolulu, HI
To understand the temporal patterns of seizure clusters treated with diazepam nasal spray rescue therapy.
Diazepam nasal spray (Valtoco®) is approved for acute treatment of seizure clusters in patients with epilepsy age ≥6 years. While early intervention for status epilepticus is considered beneficial, the impact of timing of benzodiazepine rescue treatment for seizure clusters remains unknown. 
Seizure timing data were collected during a phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray in patients aged 6–65 years with epilepsy and frequent seizure clusters; safety results were similar to diazepam rectal gel. To characterize temporal patterns, seizure-cluster data from this study were analyzed based on timing of treatment administration after seizure start: 0–5, 5–15, and >15 minutes. Data preparation included deletion of observations with seizure duration >24 hours, seizure stop time preceding start time, invalid dose date/time values, and dose date/time not within seizure start/stop time.  
Among 175 enrolled patients, 163 received ≥1 dose of diazepam nasal spray. From 4466 observations, 3225 were included in this analysis. Median time from seizure start to administration of diazepam nasal spray; from dosing to seizure cessation; and total seizure duration were 1, 2, and 4 minutes, respectively, in the 0–5 minute group. In the 5–15 minute group, median times were 6, 7, and 15 minutes, respectively. For the >15 minute group, median times were, 35, 15, and 70 minutes, respectively. 
In patients treated with diazepam nasal spray, shorter time from seizure-cluster start to treatment with diazepam nasal spray was associated with shorter time to seizure-cluster cessation and overall shorter seizure duration in this post-hoc analysis. This reinforces the value of prompt treatment, which may help minimize risk of injury and additional healthcare utilization.