(560) Impact of Seasonal Changes on the Safety and Tolerability of Diazepam Nasal Spray in Patients with Allergies or Rhinitis: Updated Interim Results From a Phase 3, Open-label, 12-Month Repeat Dose Safety Study

Rationale: Diazepam nasal spray (Valtoco^®) formulated with Intravail^® A3, a proprietary intranasal formulation indicated for acute treatment of seizure clusters in patients with epilepsy aged six years and older, provides a rapid, noninvasive, and socially acceptable route of administration. Studies have shown seasonal allergies and nasal congestion do not affect intranasal administration of agents utilizing Intravail A3, including testosterone, fentanyl, and epinephrine. This analysis evaluated the impact of a patient’s history of seasonal allergies on the safety and need for a second dose of diazepam nasal spray.

Methods: Reported here are results from an interim analysis of a Phase 3 safety study of diazepam nasal spray in epilepsy patients aged 6–65 years with seizure clusters. Age- and weight-based doses of 5, 10, 15, or 20 mg of diazepam nasal spray were administered; second doses, if needed, were to be given 4–12 hours later. Data were obtained for patients with or without a positive past medical history of seasonal allergies. The proportion of seizure events requiring a second dose of diazepam nasal spray was measured in a post hoc analysis. Safety was assessed overall and by season.

Results: A total of 177 subjects were enrolled as of the interim cutoff of October 31, 2019, and this analysis evaluated 158 patients treated with diazepam nasal spray (aged 6 to 65 years [mean, 23.5]; 53.8% female, 82.3% white). Of that population, 62 patients (39.2%; aged 6 to 59 years [mean, 22.3]; 56.5% female; 79.0% white) had medical histories that included seasonal allergies/rhinitis. This subgroup experienced 1,561 seizure episodes treated with diazepam nasal spray. Of these episodes, 173 (11.1%) required a second dose of medication: winter, 37 (11.6%); spring, 36 (9.0%); summer, 52 (10.9%); fall, 47 (13%). For comparison, in the subgroup without a history of allergies/rhinitis (n=96), there were 1,836 seizure episodes treated with diazepam nasal spray, with 143 (7.8%) requiring a second dose. Regarding safety, in the subgroup of patients with a history of allergies/rhinitis, 50 patients (80.6%) had treatment-emergent adverse events (TEAEs), with 23 (37.1%) having severe AEs (SAEs) and 12 (19.4%) having treatment-related AEs (TRAEs). In the subgroup without a history of allergies/rhinitis, 69 (71.9%) had TEAEs, with 22 (22.9%) having SAEs and 14 (14.6%) having TRAEs. The most common AEs for both groups are provided in Table 1. No SAEs were treatment related, and no patients discontinued due to a TEAE. Events by season were consistent within the two groups with minor deviations (Table 2).

Conclusions: In this interim analysis of a Phase 3 trial of diazepam nasal spray, the presence of seasonal allergies/rhinitis did not appear to influence response to medication. In both groups, repeated dosing of diazepam nasal spray demonstrated a favorable safety/tolerability profile that did not appear to be affected by the season.

Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
Click here to view image/table

Click here to view image/table