Cardiovascular Safety Results of INP104 (POD-DHE) from the STOP 301 Phase 3 Study

Poster presented at the 2021 American Headache Society (AHS) Virtual Annual Scientific Meeting.

Authors: Craig KL, Hoekman J, Jeleva M, Hocevar-Trnka J, Aurora SK, Shrewsbury SB

Introduction:

DHE product labels warn of potential cardiovascular (CV) and peripheral ischemic events despite 70+ years of clinical experience[1]. INP104 delivers DHE mesylate to the upper nasal space using a Precision Olfactory Delivery (POD®) device where it is rapidly absorbed with ~1/10th Cmax of IV DHE yet displays IV-like plasma levels from 20 minutes onwards. The STOP 101 study showed blood pressure increases with IV DHE, but not INP104. Here we present the INP104 Phase 3 CV safety results.

Objective:

To report cardiovascular results of INP104 from the STOP 301 study.

Methods:

STOP 301 was a multicenter, open-label, 24-week, intermittent INP104 use study, with a subset extending to 52-weeks (NCT0355733). Patients were allowed up to 2 doses/day of INP104, and 3 doses/week (1.45 mg per dose). Although the primary focus of this study was on nasal safety (integrity and function), CV effects (TEAEs, concomitant medication use, vital signs, and ECGs) were regularly collected and reviewed against preexisting conditions, concomitant medication use, and IP exposure.

Results:

No patients experienced cardiac TEAEs. Over 24-weeks, 5 patients (1.4%) experienced vascular TEAEs: 4 patients (1.1%) with (mild) hypertension, 3 unrelated; 2 at study start on treatment; 1 patient (0.3%) had an accidental hematoma. One patient with treated hypercholesterolemia at baseline (and possible hypertension) developed higher blood pressure on study. Three hypertensive patients completed treatment; one withdrew due to pregnancy. Inadvertent use of contraindicated medications did not reveal concerning AEs. INP104 overuse, or (contraindicated) use with triptans, did not lead to TEAEs. No serious adverse events were considered related to INP104 use.

Conclusions:

Although patients with active CV disease were excluded from the STOP 301 study, no significant AEs were noted in the peripheral or cardiovascular system even in patients with CV risk factors or concomitant triptan use. INP104 appears to be well tolerated and safe when taken as directed.

Citation:

Craig KL, Hoekman J, Jeleva M, Hocevar-Trnka J, Aurora SK, Shrewsbury SB, Cardiovascular Safety Results of INP104 (POD-DHE) from the STOP 301 Phase 3 Study, 2021 American Headache Society (AHS) Virtual Annual Scientific Meeting.

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[1] Baron, E., & Tepper, S. (2010). Revisiting the Role of Ergots in the Treatment of Migraine and Headache. Headache: The Journal of Head and Face Pain, 50(8), 1353-1361.