Abstracts

Rationale: NRL-1 (ValtocoTM) is a diazepam nasal spray formulated with Intravail® A3 that is being investigated as a rapid, non-invasive, and socially acceptable route of administration in patients with epilepsy who experience seizure emergencies despite stable regimens of antiepileptic drugs. Although it has been shown that seasonal allergies and nasal congestion do not affect intranasal administration of agents utilizing Intravail A3, including testosterone and fentanyl, the impact of a patient’s history of seasonal allergies safety and effectiveness of NRL-1 administration is presented. Methods: Reported here are results from an interim analysis of the ongoing, Phase 3, open-label study to evaluate safety/tolerability of NRL-1. Enrolled patients were adults and children/adolescents with epilepsy having seizures despite a stable anti-epileptic regimen. Informed consent was provided for all patients. Caregivers or patients administered 5, 10, 15, or 20 mg of NRL-1 (based on patient weight), with a second dose administered, if needed, 4 to 12 hours later. Investigators could adjust doses for efficacy/safety. Safety was assessed. Data were obtained for patients with or without a positive past medical history of seasonal allergies (all but 1 had ongoing allergies). Results: This analysis as of February 8, 2019, evaluated 132 patients aged 6 to 65 years (53.8% female, 82.6% white). Of that population, 27 (20.5%) patients (aged 6 to 53 years; 37.0% female; 70.4% white) had medical histories that included either seasonal allergies (n=21 [77.8%]), rhinitis (n=4 [14.8%]), allergy/chronic sinus infection (n=1 [3.7%]), or respiratory allergies (n=1 [3.7%]). This subgroup experienced 428 seizure episodes that were treated with NRL-1. Of these episodes, 14 (3.3%) required a second dose of medication. For comparison, in the subgroup without a history of seasonal allergies (n=105), there were 1838 seizure episodes treated with NRL-1, with 177 (9.6%) requiring a second dose. Regarding safety, in the subgroup of patients with a history of seasonal allergies, 19 (70.4%) had treatment-emergent adverse events (TEAEs), with 7 (25.9%) having severe AEs (SAEs) and 2 (7.4%) having treatment-related AEs (TRAEs). In the group of patients without a history of seasonal allergies, 72 (68.6%) had TEAEs, with 30 (28.6%) having SAEs and 20 (19.0%) having TRAEs. Most common AEs for both groups are provided in the Table. Conclusions: In this interim analysis of long-term safety of treatment with NRL-1, the presence of seasonal allergies did not appear to influence response to medication. In both groups, repeated dosing of NRL-1 diazepam nasal spray demonstrated a favorable safety/tolerability profile. Funding: Neurelis, Inc.