To assess the pharmacokinetics and safety of NRL-1 (Valtoco^®) in patients with epilepsy during ictal/peri-ictal and inter-ictal periods.

NRL-1 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.

Patients were diagnosed with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness. Open-label intranasal NRL-1 was administered during two periods (ictal/peri-ictal and inter-ictal) ≥14 days apart. In both periods, one dose was administered (5, 10, 15, or 20 mg; based on weight), with a second dose permitted if seizures persisted. Blood samples were taken at pre-specified timepoints after dosing, analyzed for diazepam, and pharmacokinetic measures were calculated. Safety was assessed.

The study enrolled 57 patients aged 6–59 years. The median age was 31 years (age 6–11 years, n=11; 12–16 years, n=6; >16 years, n=40), 54.4% were female, and 80.7% were white. A total of 49 patients had complete pharmacokinetic data and were included in the primary pharmacokinetic analyses. Pharmacokinetic values were similar under ictal/peri-ictal and inter-ictal conditions. Among all 57 patients, 17 (29.8%) had ≥1 treatment-emergent adverse event (TEAE). Of these, 8 patients (14%) had treatment-related TEAEs, with those reported in ≥2 patients being dysgeusia (n=3; 5.3%) and nasal discomfort (n=2; 3.5%); no local toxicity was observed. One patient had serious TEAEs (recurrent seizures, toxic encephalopathy), which were deemed unrelated to study treatment. No patient required a second dose for persistent seizures.

In this study, the epileptic condition (ictal/peri-ictal, inter-ictal) appeared to have minimal impact on intranasal NRL-1 diazepam pharmacokinetics in patients with epilepsy. NRL-1 demonstrated an acceptable safety profile.