{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:36:35Z","timestamp":1766486195936,"version":"build-2065373602"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T00:00:00Z","timestamp":1494460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004477","name":"Universiteit Stellenbosch","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004477","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Headache"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To further characterize the clinical utility of AVP\u2010825 based on additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3 comparative efficacy trial of AVP\u2010825 vs 100 mg oral sumatriptan (NCT01667679). AVP\u2010825 was approved in January 2016 by the US Food and Drug Administration under the name ONZETRA\n                      <jats:sup>\u00ae<\/jats:sup>\n                      Xsail\n                      <jats:sup>\u00ae<\/jats:sup>\n                      (sumatriptan nasal powder) for the acute treatment of migraine with or without aura in adults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>AVP\u2010825 is a delivery system that uses a patient's own breath to deliver low\u2010dose sumatriptan powder to the upper posterior regions of the nasal cavity beyond the narrow nasal valve, areas lined with vascular mucosa conducive to rapid drug absorption into the systemic circulation. The recommended dose of AVP\u2010825 is 22 mg sumatriptan powder administered as one 11 mg nosepiece in each nostril, which delivers approximately 15\u201016 mg of sumatriptan intranasally. The COMPASS trial compared AVP\u2010825 22\u2010100 mg oral sumatriptan across multiple migraine attacks for efficacy, safety, and tolerability endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/Methods<\/jats:title>\n                    <jats:p>COMPASS was a randomized, multicenter, double\u2010dummy, crossover, multiattack, comparative efficacy study with two 12\u2010week double\u2010blind periods. Patients with 2\u20108 migraine attacks\/month were randomized 1:1 to AVP\u2010825 (22 mg) plus oral placebo or an identical placebo delivery system plus 100 mg oral sumatriptan for the first period, and then patients switched treatments for the second period. Patients treated up to 5 qualifying migraines per period within 1 h of onset, even if the intensity of the attack was mild. Results from the primary endpoint (SPID\u201030, defined as the sum of pain intensity differences from dosing to 30 minutes), key secondary efficacy endpoints and safety assessments have been reported in the primary publication (Tepper et al., 2015). This article reports additional prespecified outcomes, including the SPID\u201030 for attacks treated when baseline severity was mild vs moderate\/severe, measures of sustained response and consistency of effect in patients who experienced multiple migraine attacks, and the results of post hoc analyses performed to assess total migraine freedom (defined as no pain and no migraine\u2010associated symptoms, including nausea, vomiting, photophobia, and phonophobia), time to pain freedom, time to meaningful pain relief, and local (occurring at the site of administration in the nose) vs systemic treatment\u2010emergent adverse events (TEAEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 185 patients completed both treatment periods, yielding 1,531 migraine attacks which were treated and assessed (765 AVP\u2010825, 766 oral sumatriptan). Treatment with AVP\u2010825 provided greater reduction in migraine pain intensity which was statistically significant vs oral sumatriptan in the first 30 minutes postdose regardless of whether attacks were treated when pain was mild (least squares mean SPID\u201030\u2009=\u20093.90 vs 0.24,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.0013) or moderate\/severe (least squares mean SPID\u201030\u2009=\u200913.83 vs 10.07,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.0002). At every time point from 15 to 90 minutes postdose, the proportion of attacks achieving total migraine freedom was greater and statistically significant after treatment with AVP\u2010825 vs 100 mg oral sumatriptan. AVP\u2010825 treatment resulted in greater odds of achieving pain freedom (odds ratio, OR\u2009=\u20091.29,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.01) and meaningful pain relief (OR\u2009=\u20091.32,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.0001), which were also statistically significant compared with oral sumatriptan. In addition, a greater proportion of attacks treated with AVP\u2010825 vs oral sumatriptan was associated with sustained pain freedom, achieving statistical significance when assessed from 1 h postdose through 24 hours postdose (33.3% vs 27.9%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05) and through 48 hours postdose (32.7% vs 27.4%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05). For patients who treated multiple migraine attacks in both treatment periods, a greater proportion had consistent pain relief and pain freedom following treatment with AVP\u2010825 compared to oral sumatriptan across multiple attacks, a difference that achieved statistical significance at 30 minutes postdose. Local TEAEs of abnormal taste and nasal discomfort were more common following AVP\u2010825 treatment. Of the patients experiencing either of these TEAEs, about 90% described the intensity as mild, and only one discontinued treatment because of either of these two TEAEs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results from the COMPASS study further demonstrate that treatment with AVP\u2010825 provides earlier onset and more consistent across\u2010episode improvement of pain and migraine\u2010associated symptoms compared with oral sumatriptan, highlighting the clinical advantages of this newly approved intranasal delivery system for low\u2010dose sumatriptan powder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13105","type":"journal-article","created":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T01:03:17Z","timestamp":1494550997000},"page":"862-876","source":"Crossref","is-referenced-by-count":20,"title":["Early Onset of Efficacy and Consistency of Response Across Multiple Migraine Attacks From the Randomized COMPASS Study: AVP\u2010825 Breath Powered\n                    <sup>\u00ae<\/sup>\n                    Exhalation Delivery System (Sumatriptan Nasal Powder) vs Oral Sumatriptan"],"prefix":"10.1111","volume":"57","author":[{"given":"Stephen","family":"Silberstein","sequence":"first","affiliation":[{"name":"Jefferson Headache Center Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul K.","family":"Winner","sequence":"additional","affiliation":[{"name":"Palm Beach Headache Center\/Premiere Research Institute at Palm Beach Neurology West Palm Beach FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"McAllister","sequence":"additional","affiliation":[{"name":"New England Institute for Neurology and Headache Stamford CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart 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