To evaluate the pharmacokinetics of Intravail A3 (n-dodecyl-beta-D-maltoside) after intranasal administration of NRL-1 (Valtoco^®), in patients with epilepsy who experience seizures despite stable anti-seizure drug regimens, in a phase 1 study of NRL-1 pharmacokinetics and safety.

NRL-1, a diazepam nasal spray formulated with Intravail A3 (to promote transmucosal bioavailability) provides a generally safe, rapid, non-invasive, and socially acceptable diazepam administration route for rescue medication for seizure clusters. Absorption of n-dodecyl-beta-D-maltoside through nasal mucosa occurs by paracellular transport via transient opening of tight junctions between cells and transcellular transport through cells via vesical carriers; n-dodecyl-beta-D-maltoside is “Generally Recognized as Safe” by the US FDA.

Among the total population (54.4% female, 80.7% white, mean±SD age 28.1±15.3 years), diazepam pharmacokinetics were similar in ictal/peri-ictal (n=47) and inter-ictal (n=47) periods. A maximum of 5 subjects at any timepoint had n-dodecyl-beta-D-maltoside concentrations >500 pg/mL (lower limit of quantitation [LLOQ]); maximum concentration was 741 pg/mL, and concentrations >500 pg/mL were absent by 1.75 hours postdose. Eight patients (14%) had treatment-related adverse events; those reported in ≥2 patients were dysgeusia (n=3; 5.3%) and nasal discomfort (n=2; 3.5%).