{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T20:38:27Z","timestamp":1694119107549},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Daiichi Sankyo Pharma Development"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This phase 1 single\u2010center, single\u2010dose, double\u2010dummy, placebo\u2010controlled, 4\u2010period and 4\u2010sequence crossover study assessed the potential of esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker used to treat hypertension, to affect cardiac repolarization. In this double\u2010blind study, 55 subjects were randomized to single doses of 10 mg esaxerenone (therapeutic dose), 40 mg esaxerenone (supratherapeutic dose), 400 mg moxifloxacin, or placebo. Serial electrocardiograms and pharmacokinetics (PK) were obtained over 24 and 168 hours, respectively. The primary end point was Fridericia\u2010corrected QT interval (QTcF). Secondary end points included safety and PK. Assay sensitivity was confirmed as the lower limit of 90% confidence interval (90%CIs) for placebo\u2010corrected change from baseline QTcF (\u2206\u2206QTcF) for moxifloxacin was &gt;5 milliseconds at the prespecified times; mean \u2206\u2206QTcF was 12.5 milliseconds at 3 and 4 hours postdose. The upper 90%CI limits of \u2206\u2206QTcF were \u22640 milliseconds at all times for both doses of esaxerenone. No concentration\u2010QTc relationship was identified. Therefore, esaxerenone had no potential to inhibit cardiac repolarization. No deaths or serious adverse events (AEs) occurred; 1 subject discontinued the study because of a treatment\u2010emergent AE unrelated to esaxerenone. This clinical evaluation showed that esaxerenone has no QTc prolongation potential.<\/jats:p>","DOI":"10.1002\/cpdd.794","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T13:34:21Z","timestamp":1586266461000},"page":"709-718","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Randomized, Double\u2010Blind, Single\u2010Dose, Placebo\u2010Controlled Crossover Study to Evaluate the Effects of Esaxerenone on QTc Interval in Healthy Subjects"],"prefix":"10.1002","volume":"9","author":[{"given":"Jeanne","family":"Mendell","sequence":"first","affiliation":[{"name":"Daiichi Sankyo Pharma Development  Basking Ridge New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiaki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd.  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