PHASE 1 STUDY EVALUATING THE PHARMACOKINETICS, BIOAVAILABILITY, SAFETY, AND TOLERABILITY OF INTRANASALLY ADMINISTERED EPINEPHRINE POWDER

• Published in: Annals of allergy, asthma, & immunology Vol. 133; no. 6; p. S71
• Main Authors: Francoeur, B., Wargin, W., Taubenheim, B., Lyman, S.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2024
• ISSN: 1081-1206
• DOI: 10.1016/j.anai.2024.08.235

Epinephrine is the treatment of choice for patients at risk of anaphylaxis due to severe allergies. Intranasal (IN) epinephrine powder has been developed as an alternative to the traditional intramuscular (IM) route.
This open-label, single-sequence crossover study compared a dry powder nasal epinephrine formulation (BBP01) with IM epinephrine. Healthy subjects received epinephrine 3.5 mg IN, followed by 0.3 mg IM (FDA approved dose), 0.5 mg IM (FDA requested dose), and 5.5 mg IN, with washout periods in between.
Twelve subjects enrolled, nine (75.0%) fully completed the study, while one (8%) discontinued early due to adverse events and two (17%) voluntarily withdrew. Cmax values for both IN and IM formulations increased with dose, with IN having higher values than the corresponding IM. Median Tmax values for IN were minimally 20 minutes earlier and achieved a 100 pg/ml increase from baseline (T100) more rapidly compared to IM. Correspondingly, IN displayed substantially greater pAUCs early after dosing. The relative bioavailabilities of IN epinephrine (3.5/5.5mg) versus IM (0.3mg) were 13.5% and 21.3% based on Cmax, and 11.9% and 18.8% based on AUC0-363, respectively. Pharmacodynamic analyses showed that IN administration resulted in moderate but greater increases in heart rate and systolic blood pressure compared to IM. Treatment-emergent adverse events (TEAEs) were observed more frequently in subjects receiving IN doses of epinephrine, although all TEAEs were mild or moderate in severity.
The pharmacokinetics, bioavailability and safety of IN epinephrine powder support its potential as an effective, non-invasive epinephrine delivery method.