{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:16:15Z","timestamp":1778660175446,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T00:00:00Z","timestamp":1492387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Daprodustat (GSK1278863) is a prolyl hydroxylase inhibitor in phase 3 clinical studies for the treatment of anemia associated with chronic kidney disease. This study was conducted to evaluate the effect of daprodustat on cardiac repolarization and enrolled 55 healthy adult male (29) and female (26) subjects who received single\u2010dose 75 and 500\u00a0mg daprodustat, 400\u00a0mg moxifloxacin, and placebo. Mean placebo\u2010corrected change from baseline QT interval for daprodustat showed no statistically significant increase. However, statistically significant decreases in the \u0394\u0394QTcF were observed for both doses of daprodustat, reaching a lowest value of \u20132.74 milliseconds for 75\u00a0mg and \u20135.93\u00a0milliseconds for 500\u00a0mg daprodustat; this minor shortening effect is not considered clinically significant. The moxifloxacin group showed a statistically significant increase in the \u0394\u0394QTcF value, reaching a maximal increase of 11.47 milliseconds at 4\u00a0hours. Forty subjects (73%) reported at least 1 adverse event, with the highest incidence with 500\u00a0mg daprodustat. This group had a higher incidence of gastrointestinal adverse events compared to the other treatment groups. These results suggest that 500\u00a0mg daprodustat was not well tolerated; however, daprodustat at 75\u00a0mg was generally well tolerated. No new safety concerns were identified in subjects who received 500\u00a0mg daprodustat.<\/jats:p>","DOI":"10.1002\/cpdd.342","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T15:52:41Z","timestamp":1492444361000},"page":"627-640","source":"Crossref","is-referenced-by-count":9,"title":["A Randomized, Placebo\u2010 and Positive\u2010Controlled, Single\u2010Dose, Crossover Thorough QT\/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in Healthy Subjects"],"prefix":"10.1002","volume":"6","author":[{"given":"Stephen","family":"Caltabiano","sequence":"first","affiliation":[{"name":"Metabolic Pathways and Cardiovascular GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Collins","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling &amp; Simulation GlaxoSmithKline  Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gul","family":"Serbest","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Science &amp; Study Operations GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Morgan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Science &amp; Study Operations GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modeling &amp; Simulation GlaxoSmithKline  Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramiya","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"Clinical Statistics GlaxoSmithKline  Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander R.","family":"Cobitz","sequence":"additional","affiliation":[{"name":"Metabolic Pathways and Cardiovascular GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2012.12.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2016.1182981"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111139"},{"key":"e_1_2_8_5_1","first-page":"SA","article-title":"Daprodustat, a HIF\u2010prolyl\u2010hydroxylase inhibitor, maintains hemoglobin levels over 24 weeks in anemic hemodialysis subjects switching from recombinant human erythropoietin","volume":"27","author":"Cobitz AR","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_8_6_1","first-page":"TH","article-title":"Daprodustat, a HIF\u2010prolyl\u2010hydroxylase inhibitor, increases and maintains hemoglobin over 24 weeks in anemic chronic kidney disease subjects","volume":"27","author":"Holdstock L","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706389"},{"key":"e_1_2_8_8_1","unstructured":"ICH E14: The clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs. 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