Safety of Concomitant Triptan and INP104 Use From the Phase 3 STOP 301 Study in Migraine Patients

Presented at the AHS 65^th Annual Scientific Meeting, June 15-18, 2023, Austin, Texas

Authors: Feoktistov A, Vann R, Gutierrez J, Ray S, Shrewsbury S, Aurora S

One sentence summary: The safety in migraine patients of concomitant triptan and INP104 (dihydroergotamine mesylate and Precision Olfactory Delivery) use is reported from the Phase 3 STOP 301 study.

Background: INP104 is a combination of dihydroergotamine mesylate (DHE) and Precision Olfactory Delivery approved for the acute treatment of migraine. DHE and triptans act on 5-HT1B/1D receptor subtypes, which contributes to their vasoconstrictive effects; therefore, administering 5-HT1 agonists (eg, sumatriptan) within 24 hours of DHE use is contraindicated. The safety in migraine patients who used a triptan within 24 hours of INP104 administration is reported from the STOP 301 study.

Methods: STOP 301 was a Phase 3 open-label study assessing the safety, tolerability, and exploratory efficacy of INP104 in migraine patients. Eligible patients were provided INP104 to nasally self-administer (1.45 mg) with self-recognized migraine attacks over 24 weeks, with a subset continuing to 52 weeks. Only non-ergot, non-triptan acute therapies for migraine were allowed as rescue medication within 2 hours of INP104 administration.

Results: Over 24 weeks, 354 patients self-administered ≥1 dose of INP104. Despite being instructed NOT to take triptans during the treatment period, 10 patients used triptans within 24 hours of INP104 use on ≥1 occasion. Seven of the 10 patients reported 15 treatment-emergent adverse events (TEAEs); only 2 TEAEs occurred within 24 hours of concomitant triptan and INP104 use. These included nasal congestion (possibly INP104 related) on the day of INP104 administration, which resolved before subsequent triptan use on the following day (~6 hours later) and epistaxis 2 days after concomitant triptan and INP104 use (unlikely related to INP104 or INP104/triptan use because epistaxis is not anticipated for either product). The remaining 5 patients had various TEAEs that were not temporally related to triptan and INP104 use. No TEAEs related to blood pressure, pulse, or electrocardiogram parameters were reported, and any variance was within normal clinical limits.

Conclusion: Although in a small population, the safety of concomitant triptan and INP104 use was reported, which is an important topic for the patient/physician dialogue.