A Single-Period, Single-Dose Study of the Pharmacokinetics of Epinephrine After Administration of Intranasal ARS-1 to Pediatric Subjects with a History of Systemic Allergic Reaction

An epinephrine nasal spray (ARS-1) is being developed as a needle-free alternative to autoinjectors for the emergency treatment of systemic allergic reactions including anaphylaxis in children and adults. This study aims to assess the pharmacokinetics of epinephrine after intranasal (IN) administration of ARS-1 in pediatric atopic allergy subjects. This is a single-dose open-label study in pediatric allergy subjects. Subjects with a body weight >30 kg received ARS-1 in doses of either 1.0 mg (n = 25) or 2.0 mg (n = 16). Pharmacokinetic blood samples were collected at specified intervals for 120 minutes after dosing. Safety assessments were performed before and at designated times after dosing. Mean peak plasma levels (Cmax) were 253 pg/mL following ARS-1 1.0 mg and 540 pg/mL following ARS-1 2.0 mg, demonstrating that epinephrine plasma concentrations change in a dose-proportional manner. The median time to peak plasma levels (tmax) was 20.0 minutes following ARS-1 1.0 mg and 25.0 minutes following ARS-1 2.0 mg. Both doses of ARS-1 were well tolerated. One moderate adverse event (nasal discomfort) was reported; all other events were grade 1. Following manual epinephrine IM injections 0.3 mg and EpiPen 0.3 mg in healthy adult subjects, mean Cmax values ranged from 244 to 753 pg/mL with median tmax between 5–45 minutes based on studies conducted by ARS. Administration of IN epinephrine with ARS-1 results in Cmax and tmax values similar to those observed after treatment with injection products. ARS-1 represents a safe and effective needle-free alternative to IM injection in pediatric patients.