{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:55:02Z","timestamp":1782845702841,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug\u2010device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD\u00ae).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The STOP 101 was a Phase 1 open\u2010label study that assessed the safety, tolerability, and bioavailability of INP104 1.45\u2009mg, intravenous DHE 1.0\u2009mg, and MIGRANAL (nasal DHE) 2.0\u2009mg in healthy participants. The STOP 301 was a pivotal Phase 3, open\u2010label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45\u2009mg over 24 and 52\u2009weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4\u2009mmHg, 95% confidence interval [CI] 7.9\u201315.0) and diastolic BP (13.3\u2009mmHg, 95% CI 9.4\u201317.1) at 5\u2009min post\u2010dose, persisting up to 30\u2009min post\u2010dose for systolic BP (6.3\u2009mmHg; 95% CI 3.0\u20139.5) and diastolic BP (7.9\u2009mmHg, 95% CI 3.9\u201311.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24\u2009weeks, five patients (1.4%) experienced a non\u2010serious, vascular treatment\u2010emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52\u2009weeks. Off\u2010protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV\u2010related contraindications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14669","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T04:28:20Z","timestamp":1716784100000},"page":"983-994","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (\n                    <scp>INP104<\/scp>\n                    ) for the acute treatment of migraine"],"prefix":"10.1111","volume":"64","author":[{"given":"Rima 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