Abstracts

Exploring Proposed Recommendations for Acute Cluster Treatment and Rapid and Early Seizure Termination Using Data from a Long-term Safety Study of Diazepam Nasal Spray

Abstract number : 1.407
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2024
Submission ID : 983
Source : www.aesnet.org
Presentation date : 12/7/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: Michael Chez, MD – Sutter Neuroscience Institute

Pavel Klein, MD – Mid Atlantic Epilepsy and Sleep Center
Danielle Becker, MD, MS – Department of Neurology, Ohio State University Wexner Medical Center
Jurriaan Peters, MD PhD – Boston Children’s Hospital, Harvard Medical School
Enrique Carrazana, MD – Neurelis, Inc; John A. Burns School of Medicine, University of Hawaii
Adrian Rabinowicz, MD – Neurelis, Inc.; Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, Florida Atlantic University

Rationale: Untreated seizure clusters (SCs) are associated with increased risk of emergency room use and progression to status epilepticus. Thus, appropriate prompt treatment is needed. Recent expert consensus recommendations include use of medications for acute cluster treatment (ACT) to prevent further seizures in a cluster and rapid and early seizure termination (REST) to terminate ongoing seizures. ACT medication was recommended to be administered to patients with SC when the pattern of onset is recognized. For patients with a history of prolonged seizures (PS), it was recommended that a REST medication be administered when PS onset was recognized. Examining whether a single medication might be appropriate for both ACT and REST has the potential to simplify patient care.

Methods: We examined practical application of ACT and REST using data for diazepam nasal spray from a long-term safety study. Diazepam nasal spray is approved for acute treatment of SCs in patients with epilepsy aged ≥6 years. In the study, 163 patients aged 6–65 years were administered diazepam nasal spray. Seizure start, stop, and drug administration times were recorded in a patient diary. To explore ACT, use of second doses was a proxy for effectiveness across 24 hours. REST was investigated using time from administration to SC termination; timing for termination of PS in clusters also was examined.

Results: For ACT, a single dose of diazepam nasal spray was used for the majority of SCs (3368/3853, 87.4%) across 24 hours (second doses were used for 12.6% of SCs) (Figure). As a REST therapy, administration of diazepam nasal spray (n=3225 occurrences) led to rapid SC termination. Median time to dose administration was 2 min, and the median time to seizure termination was 3 min. Most SCs were recognized quickly, and treatment was administered within 5 min (n=2169 occurrences [67.3%]). In these cases, median time to seizure termination was 2 min and most seizures terminated in < 5 min (Figure). For PS within a cluster when treatment was administered 5–15 min after the SC began (n=727 occurrences), median time to administration was 6 min, and median time to termination was 7 min. The safety profile for diazepam nasal spray was similar to that for diazepam rectal gel.

Conclusions: Findings from the large data set of the long-term study of diazepam nasal spray demonstrate that it is of benefit in immediate use for both termination of an acute SC and prevention of further seizures in SCs and prolonged seizures within SCs regardless of seizure duration (eg, PS), thus supporting the recent expert consensus recommendations. Median treatment administration was 2 min and termination was 3 min, and administration at 5–15 min was still effective in cluster treatment (ACT). Even when use diazepam nasal spray treatment was delayed, it terminated PS in a cluster in an average of 7 min. Early use of a single rescue treatment can meet the need for ACT and REST, simplifying patient education.


Funding:
Neurelis, Inc.




Anti-seizure Medications