To assess the pharmacokinetics of diazepam after single doses Valtoco™ (NRL-1; diazepam nasal spray), formulated with Intravail® A3, administered to patients with epilepsy during the ictal/peri-ictal period, and the inter-ictal period.  A secondary objective was to assess the safety and tolerability of Valtoco after intranasal administration.

Valtoco is designed as an easy-to-use, non-invasive treatment by care-partners outside the medical setting for bouts of seizures.

In this open-label study, two doses of intranasal Valtoco were administered at either 5, 10, 15, or 20 mg based on the subject’s body weight – one during the ictal/peri-ictal period and a second inter-ictally, with a minimum 14-day inter-period interval.  Blood samples were taken at various times after dosing, and analyzed for diazepam and pharmacokinetic measures calculated.

Fifty patients (including 10 pediatric) were enrolled in the study.  We report preliminary results on 34 patients (6 pediatric) for whom pharmacokinetic data are available.  No patients were discontinued.

The pharmacokinetic measures were similar in ictal/peri-ictal and inter-ictal conditions (AUC: 518 ± 30 vs. 566 ± 33 hr·ng/mL; Cmax: 156 ± 17 vs. 179 ± 18 ng/mL; tmax: 3.31 ± 2.10 vs. 2.79 ± 1.89, respectively).

Overall, twelve of the fifty patients (12 patients, 24%) experienced at least one treatment emergent adverse event (TEAE).  Dysgeusia, seizure, and nasopharyngitis were the most commonly reported AE occurrences (2 patients, 4.0% each).  One TEAE was considered severe (increase in seizures requiring use of rescue diazepam).

The PK of diazepam after intranasal administration of Valtoco in patients with epilepsy was similar in ictal/peri-ictal and inter-ictal conditions. In general, Valtoco demonstrated a good safety profile for the intended indication.