Pharmacokinetics, pharmacodynamics, and safety of AQST-109 epinephrine 12mg sublingual film: A Phase I pediatric study.

BACKGROUND

Epinephrine auto-injectors (EAI) as anaphylaxis treatment are underutilized, and administration is sometimes delayed for myriad reasons. AQST-109 is a sublingual epinephrine film in late-stage clinical development, offering a potential needle-free and highly portable alternative to EAIs.

OBJECTIVE

To evaluate AQST-109's safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile in pediatric participants, establishing a PK bridge to adult AQST-109 data.

METHODS

In this open-label Phase I study children aged 7-17 years, at-risk for a type 1 allergic reaction, received one 12mg AQST-109 film administered by healthcare provider. Primary PK endpoints included maximum plasma concentration (Cmax) and area under the curve (AUC). Additional endpoints included time to maximum plasma concentration (Tmax), heart rate (HR), systolic (SBP), diastolic blood pressure (DBP) and treatment-emergent adverse events (TEAEs).

RESULTS

Thirty-two patients received AQST-109, with 29 included in the PK analysis (n=3 with insufficient samples for analysis). Geometric mean (CV%) Cmax was 568.6 (175.8) pg/mL (7-11 years, 449.1 [94.3] pg/mL; 12-17 years, 622.1 [213.9] pg/mL). Median Tmax was 10 minutes. Geometric mean AUC0-∞ (CV%) was 440.8 (84.6) h*pg/mL (7-11 years, 418.0 [51.1]; 12-17 years, 450.7 [99.4]). Mean maximum observed effect (Emax) (SD) for HR, SBP, and DBP was 12.5 (17.3) beats, 15.4 (12.3) mmHg and 9.8 (13.6) mmHg, respectively. No severe or serious TEAEs were reported.

CONCLUSION

In children ages 7-17, a single 12-mg AQST-109 dose was well-tolerated, with rapid absorption and sustained exposure, supporting a PK bridge to adult data. AQST-109 has potential as a needle-free, sublingual alternative epinephrine treatment for severe allergic reactions in pediatric populations.