A 13.2 mg epinephrine intranasal spray demonstrates comparable pharmacokinetics, pharmacodynamics, and safety to a 0.3 mg epinephrine autoinjector

Abstract

BackgroundRecent acute anaphylaxis guideline updates have identified remaining unmet needs based on currently available therapeutic options as a critical focus. ObjectiveThe present study compares the pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of intranasal epinephrine with intramuscular epinephrine administered by autoinjector and manual syringe. MethodsAn open-label, 3-period, crossover study was conducted in 116 healthy adult volunteers to assess the bioavailability of a single intranasal dose of epinephrine, 13.2 mg compared to an intramuscular 0.3 mg autoinjector, and a 0.5 mg manual syringe. Patients achieving epinephrine concentrations of 50, 100, and 200 pg/mL at 10-, 20-, 30-, and 60-minutes post-dose were also evaluated. ResultsPK parameters for the 13.2 mg IN dose exceeded those of the 0.3 mg autoinjector with a rapid and higher Cmax (intranasal, 429.4 pg/mL and autoinjector, 328.6 pg/mL) and greater systemic exposure; AUC0-360 (intranasal=39,060 pg*min/mL, autoinjector=17,440 pg*min/mL). Similar results were observed compared to the 0.5 mg manual syringe. PK parameters for opposite and same nostril dosing were higher than both intramuscular doses, except Tmax, which was bracketed between the 2 intramusculardoses; intranasal opposite and same nostril=20 min, autoinjector=14.9 min, manual syringe=45 min. Similar effects on blood pressure and heart rate were observed for intranasal and autoinjector administration. Intranasal epinephrine was safe and well-tolerated. No serious or unexpected adverse events were reported, confirming results from earlier clinical studies. ConclusionsNDS1C addresses the unmet medical and patient needs for a needle-free, convenient, and effective dose delivery system for self-administration of epinephrine that is as good or better than the 0.3 mg autoinjector.