Objective:

To assess long-term safety and tolerability of STS101 in the acute treatment of migraine attacks.

Background:

The ASCEND study assesses the safety and tolerability of STS101 5.2 mg (dihydroergotamine nasal powder) in the acute treatment of migraine attacks with/without aura over 12 months. STS101 is a novel investigational product for rapid and easy nasal delivery.

Design/Methods:

ASCEND (NCT04406649) was a multi-center, multiple-dose, open-label 12-month study in 344 adults (18-65 years) with migraine. Participants may use up to 2 doses of STS101 within 24 hours to treat a migraine attack with up to 12 doses/month for 12 months. This interim safety analysis included those participants who exclusively used the STS101, incorporating the second-generation nasal delivery device planned for commercialization. Safety evaluations included treatment-emergent adverse event (TEAE) assessments, physical exams, vital signs, nasal exams, electrocardiograms, and lab tests.

Results:

This population included 344 adults who treated 5,571 migraine attacks with a total of 6,918 doses of STS101; the population mean±SD age was 40.4±10.9 years, 85.8% female, and 87.5% Caucasian. A total of 157 (45.6%) subjects reported TEAEs for 763 (13.7%) attacks, and 14 (4.1%) discontinued the study due to TEAEs. Most frequently reported (≥3% of subjects) related TEAEs were nasal discomfort (38 [11.0%] subjects; 338 [6.1%] attacks), dysgeusia (26 [7.6%]; 154 [2.8%]), and nasal congestion (14 [4.4%]; 198 [3.6%]); of these events, 82.7%, 16.0%, and 1.2% were mild, moderate, and severe, respectively. One serious TEAE (NSTEMI) was reported in a subject who should have been excluded from the study due to prior myocardial infarction and other conditions disqualifying for study participation. Physical exams, vital signs, nasal exams, electrocardiograms, and lab tests did not show any clinically relevant findings.

Conclusions: