Potential Adverse Events of Clinical Interest with Use of Diazepam Nasal Spray in Children: Interim Results from an Ongoing Open-label, Pharmacokinetic and Safety Study
Abstract number :
2.368
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
1170
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Muhammad Zafar, MD, FACNS – Duke University Hospital
Eric Segal, MD – Hackensack University Medical Center, Hackensack Meridian School of Health, and Northeast Regional Epilepsy Group
James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES – LeBonheur Children’s Hospital
Evelyn Shih, MD, PhD – Neurelis, Inc.
Leock Ngo, PhD – Neurelis, Inc.
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: Some people with epilepsy experience seizure clusters despite daily antiseizure medication(s). Benzodiazepines are the cornerstone of acute treatment for seizure clusters; however, children age 2–5 years with seizure clusters have limited treatment options. Diazepam nasal spray (Valtoco®) is approved for acute treatment of seizure clusters in patients with epilepsy age ≥6 years. Here, we present the interim results for adverse events of special interest related to the drug and route of administration from an ongoing phase 1/2a study of the pharmacokinetics (PK) and safety of diazepam nasal spray in children aged 2–5 years.
Methods: This ongoing study included single-dose PK and open-label safety periods. Pediatric patients aged 2–5 years with epilepsy and seizure clusters were included. Study personnel/caregivers were trained to administer diazepam nasal spray (0.5 mg/kg) in weight-based doses of 5, 10, or 15 mg; second doses 4–12 hours after the first dose were permitted, if needed. Investigators could adjust dose. Data related to the seizure (eg, date, time of onset, duration) and time of dosing were recorded in an electronic diary. Treatment-emergent adverse events (TEAEs), vital signs, and laboratory tests were evaluated; TEAEs of special interest to clinicians include nasal irritation and respiratory depression.
Results: Of the 35 patients enrolled, 31 (88.6%) completed the 180-day open-label safety period as of October 24, 2023 (data cutoff). The majority of patients were male (60.0%), with a mean (SD) age of 3.9 (1.0) years. Patients had received a mean of 8.54 (11.20) doses over the 180-day treatment period and an average of 1.45 (1.85) doses/month. Twenty-four patients (68.6%) had ≥1 TEAE during the open-label safety period, 10 (28.6%) ≥1 serious TEAE, and 7 (20.0%) ≥1 treatment-related TEAE. No patients discontinued due to a TEAE, and there were no deaths. Treatment-related TEAEs were nasal mucosal disorder, nasal edema, rhinorrhea, blepharitis, vomiting, administration site pain, pneumonia aspiration, and somnolence (n=1 [2.9%] each). Respiratory depression, respiratory distress, hypoxia, and respiratory failure were reported by 1 patient each; none were attributed to treatment. Changes in vital signs reported as TEAEs during the study (fever/pyrexia) were deemed unrelated to treatment. Only 1 clinically significant abnormal laboratory value was identified after screening (elevated leukocyte level), which was attributed to an infection. Nasal irritation was infrequent and mild (Table 1).
Conclusions: In this interim analysis, there were no new safety signals of clinical interest with diazepam nasal spray in children aged 2–5 years. Adverse events associated with benzodiazepines (eg, somnolence) and the route of administration (eg, nasal irritation) were uncommon, and cardiorespiratory adverse events were not related to treatment. Moreover, diazepam nasal spray was not associated with changes in vital signs or laboratory values.
Funding: Neurelis, Inc.
Anti-seizure Medications