{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:09Z","timestamp":1786977549754,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T00:00:00Z","timestamp":1567036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013993","name":"Theravance Biopharma US","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Revefenacin is a novel once\u2010daily, lung\u2010selective, long\u2010acting muscarinic antagonist developed as a nebulized inhalation solution for the maintenance treatment of chronic obstructive pulmonary disease. In a randomized, 4\u2010way crossover study, healthy subjects received a single inhaled dose of revefenacin 175\u00a0\u00b5g (therapeutic dose), revefenacin 700\u00a0\u00b5g (supratherapeutic dose), and placebo via standard jet nebulizer, and a single oral dose of moxifloxacin 400\u00a0mg (open\u2010label) in separate treatment periods. Electrocardiograms were recorded, and pharmacokinetic samples were collected serially after dosing. The primary end point was the placebo\u2010corrected change from baseline QT interval corrected for heart rate using Fridericia's formula, analyzed at each postdose time. Concentration\u2010QTc modeling was also performed. Following administration of revefenacin 175\u00a0 and 700\u00a0\u00b5g, placebo\u2010corrected change from baseline QTcF (\u0394\u0394QTcF) values were close to 0 at all times, with the largest mean \u0394\u0394QTcF of 1.0 millisecond (95% confidence interval [CI], \u22121.2 to 3.1 milliseconds) 8 hours postdose and 1.0 millisecond (95%CI, \u22121.1 to 3.1 milliseconds) 1 hour postdose after inhalation of revefenacin 175\u00a0and 700\u00a0\u00b5g, respectively. Revefenacin did not have a clinically meaningful effect on heart rate (within \u00b15 beats per minute of placebo), or PR and QRS intervals (within \u00b13 and \u00b11 milliseconds of placebo, respectively). Using concentration\u2010QTc modeling, an effect of revefenacin &gt; 10 milliseconds can be excluded within the observed plasma concentration range of up to \u22483\u00a0ng\/mL. Both doses of revefenacin were well tolerated. These results demonstrate that revefenacin does not prolong the QT interval.<\/jats:p>","DOI":"10.1002\/cpdd.732","type":"journal-article","created":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T01:15:36Z","timestamp":1567127736000},"page":"130-139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Revefenacin, a Long\u2010Acting Muscarinic Antagonist, Does Not Prolong QT Interval in Healthy Subjects: Results of a Placebo\u2010 and Positive\u2010Controlled Thorough QT Study"],"prefix":"10.1002","volume":"9","author":[{"given":"Marie T.","family":"Borin","sequence":"first","affiliation":[{"name":"Theravance Biopharma US, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris N.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Theravance Biopharma US, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borje","family":"Darpo","sequence":"additional","affiliation":[{"name":"ERT, previously iCardiac Technologies  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Pendyala","sequence":"additional","affiliation":[{"name":"Theravance Biopharma US, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqi","family":"Xue","sequence":"additional","affiliation":[{"name":"ERT, previously iCardiac Technologies  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Bourdet","sequence":"additional","affiliation":[{"name":"Theravance Biopharma US, Inc.  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