Integrated Phase I Pharmacokinetics and Pharmacodynamics of Epinephrine Administered via Sublingual Film, Autoinjector, or Manual Injection

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered via intramuscular (IM) or subcutaneous (SC) injection. AQST-109, a sublingual film containing a prodrug of epinephrine, is in development as an alternative delivery method for the treatment of severe allergic reactions including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine following administration of AQST-109 to epinephrine delivered by manual IM injection and epinephrine autoinjectors (EAIs).

Methods: Data were integrated from two randomized, open-label, Phase I crossover trials evaluating the pharmacokinetics and pharmacodynamics of epinephrine in 54 healthy volunteers. They had no prior medical conditions and were delivered either AQST-109 12 mg or 0.3 mg EpiPen, 0.3 mg generic EpiPen, 0.3 mg Auvi-Q and 0.3 mg manual IM injection.

Results: AQST-109 yielded comparable epinephrine pharmacokinetics and similar exposure when compared to both the manual IM injection and EAIs. The median time to maximum concentration (Tmax) for AQST-109 was 15 minutes, as compared to EpiPen (10 minutes), generic EpiPen (15 minutes), Auvi-Q (30 minutes) and manual IM (50 minutes). There was also an early, rapid, and consistent increase observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) following the administration of AQST-109.

Conclusion: AQST-109 delivered epinephrine with PK and PD results within the bracketed range of approved IM products. AQST-109 shows promise as an innovative, needle-free, non-device, portable and orally delivered alternative for the first-line treatment of Type I allergic reactions, including anaphylaxis.