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Abstract Details

Comparison of Early Plasma Exposure to DHE for Marketed and Development Stage Nasal, Inhalation, and Injectable Products
Headache
P14 - Poster Session 14 (8:00 AM-9:00 AM)
7-009

To compare AUC0-2hr and AEs of INP104 (dihydroergotamine mesylate [DHE] by Precision Olfactory Delivery [POD®]), Migranal® Nasal Spray, D.H.E. 45® (IV), STS101 (nasal powder), and MAP0004 (inhalation) using STOP 101 study data and literature reports.

DHE plasma exposure in the first 2 hours is critical to migraine pain relief, justifying an emphasis on AUC0–2hr when assessing novel DHE products. Research suggests Cmax has a lower efficacy correlation and that high IV Cmax may predict more AEs.
PK results from STOP 101 where INP104 (1.45 mg), Migranal (2 mg), or D.H.E. 45 (IV) (1 mg) were administered in a 3-way, 3-period crossover were compared to results in literature reports for STS101 (6 mg) and MAP0004 (1 or 2 mg). Trends of DHE PK, efficacy, and AEs related to AUC0-2hr and Cmax reported were reviewed and are described.
AUC0-2hr following administration of INP104, Migranal, and D.H.E. 45 (IV) was 1,603, 387.5, and 3,022 hr*pg/mL, respectively, in the STOP 101 trial. Cmax values were highest following IV DHE at 14,190 pg/mL followed by INP104 (1,301 pg/mL) and Migranal (299.6 pg/mL). AEs were highest for IV DHE and similar for INP104 and Migranal, despite the substantial difference in plasma exposure. Published reports for STS101 and MAP0004 report AUC0-2hr values of 2,979 and 1,447 hr*pg/mL, respectively. One literature report with MAP0004 reports that increasing dose 1 mg to 2 mg provides increased plasma levels, more AEs and a decrease in therapeutic gain.
DHE AUC0-2hr exceeding ~1,500 hr*pg/mL and high Cmax values may result in more AEs without enhanced efficacy and could even result in decreased efficacy. INP104 AUC0-2hr potentially enables rapid and sustained pain relief, as validated by the MAP0004 clinical program. The lower Cmax following INP104 treatment vs IV may lead to improved tolerability.
Authors/Disclosures
Kelsey Satterly
PRESENTER 		Kelsey Satterly has received personal compensation for serving as an employee of Impel NeuroPharma . Kelsey Satterly has received intellectual property interests from a discovery or technology relating to health care.
Stephen B. Shrewsbury, MD (Impel Pharmaceuticals) Dr. Shrewsbury has received personal compensation for serving as an employee of Impel NeuroPharma. Dr. Shrewsbury has received stock or an ownership interest from Impel NeuroPharma.
No disclosure on file