This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD)
subjects with anemia associated with chronic kidney disease (CKD), designed to compare the
effects of daprodustat to epoetin alfa on blood pressure (BP). Subjects will be screened for
eligibility within 7 and 30 days prior to erythropoesis-stimulating agent (ESA) washout.
Following a 2-week ESA washout period, on Day 1 subjects will be randomized 1:1 and
stratified by prior ESA dose before they undergo Acute Challenge 1, a single dose challenge
to compare the acute effects on BP of the highest planned once-daily maintenance dose of
daprodustat (24 milligrams [mg]) to the highest starting dose of epoetin alfa (100
international units [IU]/kilograms [kg]). This will be followed by an 8-week hemoglobin
(Hgb)-maintenance period, where doses of either daprodustat or epoetin alfa will be
administered and adjusted. At the end of Hgb maintenance period, on Day 57 an Acute Challenge
(number 2) will be repeated utilizing the same treatment dose administered in Acute Challenge
1; there will be a follow-up visit within 14+/-3 days after completing treatment. The total
duration of subject involvement is up to 16 weeks (Screening to Follow-up).