Abstracts

Safety Profile of Diazepam Nasal Spray in Patients Aged 2–5 Years from an Ongoing, Open-label 180-day Safety Period Following Pharmacokinetic Sampling in a Phase 1/2a Study

Abstract number : 2.371
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2024
Submission ID : 915
Source : www.aesnet.org
Presentation date : 12/8/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: Evelyn Shih, MD, PhD – Neurelis, Inc.

James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES – LeBonheur Children’s Hospital
Eric Segal, MD – Hackensack University Medical Center, Hackensack Meridian School of Health, and Northeast Regional Epilepsy Group
Muhammad Zafar, MD, FACNS – Duke University Hospital
Leock Ngo, PhD – Neurelis, Inc.
Adrian Rabinowicz, MD – Neurelis, Inc.; Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, Florida Atlantic University
Enrique Carrazana, MD – Neurelis, Inc; John A. Burns School of Medicine, University of Hawaii

Rationale: For pediatric patients with epilepsy aged 2 to 5 years, diazepam rectal gel has been the only immediate-use antiseizure medication approved by the US Food and Drug Administration (FDA) for the treatment of seizure clusters; diazepam buccal film was recently approved. Despite its efficacy and safety profile, rectal administration requires multiple steps to position the patient and to prepare the drug, which may delay treatment. Diazepam nasal spray is approved by the FDA for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years, does not require positioning the patient, needs fewer steps to administer, and has an established safety profile consistent with rectal diazepam in children aged ≥6 years and adults.


Methods: Patients aged 2 to 5 years with epilepsy and seizure clusters were enrolled in an ongoing phase 1/2a, open-label, single-dose pharmacokinetics (PK) study of diazepam nasal spray with a 180-day open-label safety period. Doses were based on the patient’s body weight (0.5 mg/kg). Following a single dose for PK sampling, caregivers were supplied with diazepam nasal spray to use as indicated on an as-needed basis for immediate-use treatment of seizure clusters during the safety period. Seizures and dose administrations were recorded in a diary, and patients returned to the site on days 30, 90, and 180 for safety evaluations, including recording treatment-emergent adverse events (TEAEs).


Results: The study enrolled 35 patients; 31 (88.6%) completed the 180-day safety period as of October 2023. Mean age was 3.9 years (range: 2.0–5.8 y); 18 (51.4%) and 17 (48.6%) patients were 2–3 years and 4–5 years, respectively. A total of 299 doses were administered (5 mg, 11 doses [n=3 patients]; 10 mg, 238 doses [n=28]; 15 mg, 50 doses [n=4]). A total of 24 patients (68.6%) reported a TEAE (Table). Serious TEAEs were reported in 10 patients (28.6%); none were deemed treatment related. Treatment-related TEAEs were reported in 7 patients (20.0%), with occurrence in only a single patient each. A respiratory depression event with an outcome of recovered/resolved was reported for 1 patient; this event was not considered treatment related. Of the 4 patients who discontinued prematurely, 2 patients were lost to follow-up, 1 patient withdrew consent, and 1 patient was discontinued owing to inadequate treatment effect. There were no TEAEs that led to discontinuation or death.

Conclusions: Thirty-five patients aged 2 to 5 years were enrolled in a phase 1/2a, open-label, single-dose PK study of diazepam nasal spray with a 180-day open-label safety period. In this ongoing study, 88.6% of patients completed the safety period. Treatment-related TEAEs were reported in 20.0% of patients, none of which were serious. There were no discontinuations owing to TEAEs. The safety profile of diazepam nasal spray was generally consistent with that of older patients and supports use in this age group.

Funding: Neurelis, Inc.

Anti-seizure Medications