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. The purpose of this study was to evaluate the safety/tolerability of NRL-1 (intranasal diazepam) over 12 months in patients treated for cluster or acute repetitive seizures. Methods: Reported here are results from an interim analysis of the ongoing, Phase 3, open-label study. Enrolled patients were adults and children/adolescents with epilepsy having seizures despite a stable anti-epileptic regimen. Informed consent was provided for all patients. Patients or caregivers administered 5, 10, 15, or 20 mg of NRL-1 (based on patient weight), with a second dose administered, if needed, 4–12 hours later. Investigators could adjust doses for efficacy/safety. Safety measures included treatment-emergent adverse events (TEAEs), physical/neurological examination, vital signs, laboratory tests, nasal irritation, and smell tests. Results: This analysis evaluated 132 patients aged 6 to 65 years (53.8% female, 82.6% white). Among these patients, 18 (13.6%) had exposure <6 months, 47 (35.6%) had exposure 6 to <12 months, and 67 (50.8%) had exposure ≥12 months. Also, 77 (58.3%) patients averaged ≥2 doses per month. A total of 91 (68.9%) patients had ≥1 TEAE (Table). Of these, 37 (28.0%) patients had serious TEAEs; none of the serious TEAEs was deemed related to study drug. No trends were observed in the incidence of the most frequent TEAEs (Table). TEAEs assessed by investigators as being at least possibly treatment-related (Table) in ≥2% of patients were nasal discomfort (5.3%), headache (3.0%), and epistaxis (2.3%). Few patients reported nasal irritation; smell tests showed no clinically relevant olfactory changes. There were no trends in effects on hematology, chemistry, or urinalysis values; and no electrocardiographic abnormalities were observed. More than 90% of patients remain in this long-term study. Of the 13 who discontinued, 10 were due to withdrawal by subject, 1 due to a serious adverse event by physician decision, 1 was lost to follow-up, and 1 moved out of state. Conclusions: In this interim analysis of long-term safety, repeated dosing of NRL-1 diazepam nasal spray demonstrated a favorable safety/tolerability profile in patients with epilepsy. Funding: Neurelis, Inc.