Anemia Studies in Chronic Kidney Disease: Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Dialysis (ASCEND-D)

Inclusion Criteria:

• Age: 18 to 99 years of age (inclusive).
• Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6weeks prior to screening and between screening and randomization.
• Hgb concentration: On Week -8: Hgb 8 to 12 grams per deciliter (g/dL). Onrandomization (Day 1): Hgb 8 to 11 g/dL and receiving at least the minimum ESA dose.Hgb >11 g/dL to 11.5 g/dL and receiving greater than the minimum ESA dose.
• Dialysis: On dialysis >90 days prior to screening and continuing on the same mode ofdialysis from screening (Week -8) through to randomization (Day 1).
• Frequency of Dialysis: Hemodialysis (HD) >=2 times/week and peritoneal dialysis (PD) >=5 times/week. Home hemodialysis >=2 times/week.
• Compliance with placebo [randomization (Day 1) only]: >=80% and <=120% compliance withplacebo during run-in period.
• Informed consent (screening only): capable of giving signed informed consent whichincludes compliance with the requirements and restrictions listed in the consent formand in this protocol.

Exclusion Criteria:

• Kidney transplant: Planned living-related or living-unrelated kidney transplant within 52 weeks after study start (Day 1).
• Ferritin: <=100 nanograms (ng)/milliliter (mL) (<=100 micrograms/liter [L]) atscreening.
• Transferrin saturation (TSAT) (screening only): <=20%.
• Aplasias: History of bone marrow aplasia or pure red cell aplasia.
• Other causes of anemia: Untreated Pernicious anemia, thalassemia major, sickle celldisease or myelodysplastic syndrome.
• Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, oresophageal ulcer disease or clinically significant GI bleeding <=4 weeks prior toscreening through to randomization (Day 1).
• MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization (Day 1).
• Stroke or transient ischemic attack: <=4 weeks prior to screening through torandomization (Day 1).
• Heart failure (HF): Chronic Class IV HF, as defined by the New York Heart Association (NYHA) functional classification system.
• Current uncontrolled hypertension: Current uncontrolled hypertension as determined bythe investigator that would contraindicate the use of recombinant human erythropoietin (rhEPO).
• Bazett's corrected QT interval (QTcB) (Day 1): QTcB >500 millisecond (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QT Interval Corrected forHeart Rate (QTc) exclusion for subjects with a predominantly ventricular paced rhythm.
• Alanine transaminase (ALT): >2x upper limit of normal (ULN) at screening.
• Bilirubin: >1.5xULN at screening.
• Current unstable liver or biliary disease per investigator assessment, generallydefined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia,esophageal or gastric varices, persistent jaundice, or cirrhosis.
• Malignancy: History of malignancy within the 2 years prior to screening through torandomization (Day 1) or currently receiving treatment for cancer, or complex kidneycyst (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with theexception of localized squamous cell or basal cell carcinoma of the skin that has beendefinitively treated >=4 weeks prior to screening.
• Severe allergic reactions: History of severe allergic or anaphylactic reactions orhypersensitivity to excipients in the investigational product, or epoetin alfa ordarbepoetin alfa.
• Drugs and supplements: Use of strong inhibitors of Cytochrome P4502C8 (CYP2C8) (e.g.,gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
• Other study participation: Use of other investigational agent or device prior toscreening through to randomization (Day 1).
• Prior treatment with daprodustat: Any prior treatment with daprodustat for treatmentduration of >30 days.
• Females only: Subject is pregnant [as confirmed by a positive serum human chorionicgonadotrophin (hCG) test for females of reproductive potential (FRP) only], subject isbreastfeeding, or subject is of reproductive potential and does not agree to followone of the contraceptive options listed in the List of Highly Effective Methods forAvoiding Pregnancy.
• Other Conditions: Any other condition, clinical or laboratory abnormality, orexamination finding that the investigator considers would put the subject atunacceptable risk, which may affect study compliance (e.g., intolerance to rhEPO) orprevent understanding of the aims or investigational procedures or possibleconsequences of the study.