{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:48:23Z","timestamp":1791312503214,"version":"4.3.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100020141","name":"Akebia Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two Phase 2, multicenter, double-blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n\u2009=\u200951) or dialysis-dependent (DD, n\u2009=\u200960) CKD-induced anemia to once-daily vadadustat (150, 300 or 600\u2009mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment\/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from pretreatment to Week 6.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Statistically significant (P\u2009&amp;lt;\u20090.01) dose-dependent increases in mean Hb values were observed at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 300 and 600\u2009mg: \u22120.47, 0.43, 1.13 and 1.62 (NDD-CKD) and \u22121.48, \u22120.28, 0.08 and 0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of vadadustat-treated participants achieved target Hb levels (10.0\u201312.0\u2009g\/dL) and significant dose-dependent changes in iron utilization and mobilization biomarkers were observed with vadadustat. During the primary efficacy period, the incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 150, 300 and 600\u2009mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% (DD-CKD), respectively. The most common AEs during the primary efficacy period were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related (hepatic function abnormal); no deaths were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The efficacy and safety results from these studies support the development of vadadustat for the treatment of anemia in patients with CKD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfaa060","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T20:23:42Z","timestamp":1583958222000},"page":"1244-1252","source":"Crossref","is-referenced-by-count":42,"title":["Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients"],"prefix":"10.1093","volume":"36","author":[{"given":"Masaomi","family":"Nangaku","sequence":"first","affiliation":[{"name":"Graduate School of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef M K","family":"Farag","sequence":"additional","affiliation":[{"name":"Clinical Development, Akebia Therapeutics Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"deGoma","sequence":"additional","affiliation":[{"name":"Akebia Therapeutics Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Luo","sequence":"additional","affiliation":[{"name":"Biostatistics, Akebia Therapeutics Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Vargo","sequence":"additional","affiliation":[{"name":"Clinical Development, Akebia Therapeutics Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshan","family":"Khawaja","sequence":"additional","affiliation":[{"name":"Drug Safety and 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