BACKGROUND: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl 
hydroxylase inhibitor being developed for treatment of anemia associated with 
chronic kidney disease (CKD). The effect of daprodustat in Japanese CKD patients 
with anemia has not been previously investigated.
METHODS: We evaluated the relationship between daprodustat dose and hemoglobin 
response in Japanese patients on hemodialysis (HD) with anemia in a 4-week, 
phase II, double-blind, placebo-controlled study. After interrupting their 
erythropoiesis-stimulating agent for between 2 and 8 weeks, subjects with 
hemoglobin 8.5-10.5 g/dL were randomized to placebo or daprodustat 4, 6, 8, or 
10 mg orally once daily. Hemoglobin, erythropoietin (EPO), and vascular 
endothelial growth factor (VEGF) levels during therapy were evaluated.
RESULTS: Eighty-six of 97 randomized subjects completed the study. Mean baseline 
hemoglobin ranged from 9.68 to 9.92 g/dL across groups. After 4-week 
administration, mean hemoglobin changes were -0.28, -0.01, 0.54, and 0.97 g/dL 
in the 4, 6, 8, and 10 mg groups, respectively, as compared to -1.41 g/dL for 
placebo. Dose-dependent increase in plasma EPO concentration were observed up to 
8 mg, with the 10 mg dose responses being similar to 8 mg. Plasma VEGF 
concentrations were minimally changed, even though 5 subjects treated with 6-10 
mg reached EPO >500 mIU/mL.
CONCLUSION: Daprodustat 4-10 mg once-daily produced dose-dependent increase in 
hemoglobin relative to placebo in Japanese HD subjects. The doses evaluated in 
the study have moderately increased endogenous EPO without changes in 
circulating VEGF levels.