Lack of Impact of Seasonal Allergies/Rhinitis History on Safety of Diazepam Nasal Spray in Patients with Seizure Clusters: Final Results from a Long-Term, Phase 3, Open-Label, Repeat-Dose Safety Study
Abstract number :
2.214
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825579
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:43 AM
Authors :
Blanca Vazquez, MD - New York University, Comprehensive Epilepsy Center; James Wheless, MD - Le Bonheur Children’s Hospital, University of Tennessee Health Science Center; Jay Desai, MD - Children’s Hospital of Los Angeles; Adrian Rabinowicz, MD - Neurelis, Inc.; Enrique Carrazana, MD - Neurelis, Inc.
Rationale: As seasonal allergies are associated with nasal inflammation, it is important to establish that the safety of intranasal seizure rescue medications is not impacted by seasonal allergies. Diazepam nasal spray (Valtoco®) is formulated with Intravail® A3 (to enhance absorption) and vitamin E (to enhance solubility) to provide a rapid and noninvasive route of diazepam administration for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Presented here are the final results of an exploratory analysis from the long-term, phase 3, open-label, repeat-dose safety study evaluating the impact of seasonal allergies or rhinitis history on the safety profile of diazepam nasal spray. The current investigation, with longer patient exposure across the seasons, updates a prior interim analysis.
Methods: Eligible patients were aged 6–65 years with a diagnosis of partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness who experienced seizure clusters. Patients and care partners were trained to administer age- and weight-based doses of 5, 10, 15, or 20 mg of diazepam nasal spray, with a second dose administered 4–12 hours later, if needed. Treatment-emergent adverse events (TEAEs) were recorded in a diary, and relationship to study drug was assessed. For this analysis, safety data were evaluated for subgroups of patients with or without seasonal allergies or rhinitis history, assessed overall and by season.
Results: Of 175 patients enrolled in the study, 163 received ≥1 dose of diazepam nasal spray (54.6% female; mean age, 23.1 years) and were included in the safety population. Duration of exposure to diazepam nasal spray was ≥12 months (ie, across all 4 seasons) in 81.6% of these patients. Within the safety population, 70 (42.9%) had seasonal allergies or rhinitis history. In this subgroup, 60 (85.7%) had TEAEs, 26 (37.1%) had serious TEAEs, 15 (21.4%) had treatment-related TEAEs, and one patient discontinued from the study due to a TEAE that was not treatment-related (Table 1). In the subgroup of patients without allergies (n=93 [57.1%]), a total of 74 (79.6%) had TEAEs, 24 (25.8%) had serious TEAEs, and 15 (16.1%) had treatment-related TEAEs; in this subgroup, there was one death, which was not deemed treatment-related. There were no serious treatment-related TEAEs in either subgroup. Rates of TEAEs and treatment related TEAEs in the allergies subgroup were similar across the seasons (Table 2).
Conclusions: In patients with or without history of seasonal allergies, diazepam nasal spray demonstrated a safety profile consistent across the reported patients, with no unforeseen TEAEs compared with those reported for previous diazepam formulations for treatment of seizure clusters. In the subgroup with allergies, a rates of TEAEs were similar across the seasons.
Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
Anti-seizure Medications