Shorter Time to Treatment Is Associated with Faster Time to Termination of Seizure Clusters in Multiple Subpopulations Treated with Diazepam Nasal Spray
Abstract number :
2.265
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2023
Submission ID :
598
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Danielle A. Becker, MD, MS – The Ohio State University Wexner Medical Center
Randa Jarrar, MD – Phoenix Children’s Hospital, Phoenix, Arizona, USA; John Stern, MD – Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA; Sunita Misra, MD, PhD – Neurelis, Inc., San Diego, California, USA; Adrian Rabinowicz, MD – Neurelis, Inc., San Diego, California, USA; Enrique Carrazana, MD – Neurelis, Inc., San Diego, California, USA; John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA
Rationale: Diazepam nasal spray (Valtoco®) is approved in the United States for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Although early intervention for status epilepticus is considered beneficial, the impact of timing of benzodiazepine rescue treatment for seizure clusters remains unknown. This post hoc analysis investigated the temporal patterns of seizure clusters treated with diazepam nasal spray in different patient subpopulations, including those with ≥20 recorded seizure clusters and in adult and pediatric patients.
Methods: 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 was similar to diazepam rectal gel. To characterize temporal patterns, seizure cluster data recorded in seizure diaries were analyzed based on the timing of treatment administration after seizure start. Data preparation included exclusion of observations with seizure duration >24 hours, negative duration, and invalid dose date/time values. Medians were calculated.
Results: Among 175 enrolled patients, 163 received ≥1 dose of diazepam nasal spray. From 4466 observations, 3225 were included in this analysis. Overall, median time (range) from seizure start to administration of diazepam nasal spray was 2 minutes (0–750); from dosing to seizure termination, 3 minutes (0–1440); and for total seizure duration, 7 minutes (0–1440). In the group receiving diazepam nasal spray in < 5 minutes (n=2169 observations), median time (range) to dose was 1 minute (0–4); dosing to seizure termination, 2 minutes (0–1440); and total seizure duration, 4 minutes (0–1440). In the ≥5-minute group (n=1056 observations), median time (range) to dose was 10 minutes (5–750); dosing to seizure termination, 10 minutes (0–1150); and total seizure duration, 23 minutes (5–1170). A subset of patients with ≥20 observations (n=2484 total observations from 61 patients) was analyzed. Among those in this group treated in < 5 minutes, median time to dose was 1 minute; dosing to seizure termination, 3 minutes; and total seizure duration, 4 minutes. For those treated in ≥5 minutes, median time to dose was 10 minutes; dosing to seizure termination, 11 minutes; and total seizure duration, 25 minutes. Similar results were observed in adult (18–65 years; n=1567 observations) and pediatric patients (6–17 years; n=1658 observations).
Conclusions: In a real-world setting, shorter time (< 5 minutes) to treatment with diazepam nasal spray was associated with shorter time to seizure cluster termination and overall shorter seizure duration. This was observed in the overall study population with seizure clusters, a group with a large number of treated seizure clusters, and in adults and pediatric patients. This post hoc analysis supports the applicability of these findings to multiple populations and reinforces the value of prompt recognition and treatment intervention, which may help minimize risk of injury and additional healthcare utilization.
Funding: Neurelis, Inc.
Anti-seizure Medications