{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:55:17Z","timestamp":1789239317411,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T00:00:00Z","timestamp":1549324800000},"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","award":["NCT 01831804"],"award-info":[{"award-number":["NCT 01831804"]}],"id":[{"id":"10.13039\/100004330","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":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Daprodustat, a small\u2010molecule inhibitor of prolyl hydroxylases, prevents breakdown of hypoxia\u2010inducible factor (HIF), leading to increased transcription of HIF\u2010responsive genes. This randomized, placebo\u2010controlled study evaluated the safety, tolerability, and pharmacokinetics of a topical formulation of daprodustat in healthy volunteers (intact skin) and in patients with diabetic foot ulcers (DFUs) following single and\/or 14\u2010day repeat\u2010dose administration. In the diabetic patients, exploratory assessments of wound area, volume, and depth were made to qualitatively assess effectiveness. Systemic absorption via topical application was limited across doses up to 1.0% at 100 mg\/cm<jats:sup>2<\/jats:sup> for 14 days. Systemic pharmacokinetics were quantifiable in a few samples from a few patients. Because only sporadic concentrations were observed versus pharmacokinetic profiles, pharmacokinetic parameters were not determined. Wound area, depth, and volume showed consistent but weak improvements in the treatment arm; however, the variability in response and small sample size of the standard\u2010of\u2010care and placebo arms limited the ability to assess trends in wound healing compared with the daprodustat arm. Overall, topically applied daprodustat was well tolerated, raised no safety concerns, and provided limited to nonquantifiable systemic exposures. The healing of DFUs will need to be evaluated in studies designed to test this hypothesis over a longer treatment duration.<\/jats:p>","DOI":"10.1002\/cpdd.654","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T17:46:55Z","timestamp":1549388815000},"page":"765-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Randomized Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Topical Daprodustat in Healthy Volunteers and in Patients With Diabetic Foot Ulcers"],"prefix":"10.1002","volume":"8","author":[{"given":"Eric","family":"Olson","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Mahar","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Morgan","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fillmore","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Holland","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Lavery","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center at Dallas  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13680"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/107110070602700408"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0344"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1067-2516(07)60001-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.332.7546.900"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1075"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29710"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601579"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906670106"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.4962"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2066"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104731"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.51.32529"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.047"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.715847"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.109041"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066373"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/b701676j"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890801986594"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209789649457"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.914801"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0520"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2011.00697.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.327"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.83"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.242503"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2015.11.021"},{"key":"e_1_2_10_29_1","first-page":"1","article-title":"Daprodustat for anemia: a 24\u2010week, open\u2010label, randomized controlled trial in participants with chronic kidney disease","author":"Holdstock L","year":"2018","journal-title":"Clin Kidney J"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111139"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2015.08.004"},{"key":"e_1_2_10_32_1","unstructured":"GlaxoSmithKline.A first\u2010time in human study to investigate the safety tolerability pharmacokinetics and pharmacodynamics of GSK1278863A in healthy subjects.https:\/\/www.gsk-studyregister.com\/study\/8400. 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