This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD)
participants with anemia associated with chronic kidney disease (CKD), designed to compare
the effects of daprodustat to epoetin alfa on blood pressure (BP). Participants 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 participants 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
units/kilogram [U/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 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.