This study will be conducted to assess the pharmacokinetics of vadadustat 600, 750, and 900 milligrams daily, and intravenous erythropoiesis-stimulating agent (darbepoetin alfa or epoetin alfa), in hemodialysis participants with anemia associated with chronic kidney disease.

Inclusion Criteria:

• Male or female ≥18 years of age at the time of informed consent
• Receiving chronic, outpatient in-center hemodialysis three times a week for end-stage renal disease for at least 12 weeks prior to Screening
• Maintained on intravenous erythropoiesis-stimulating agent (ESA) therapy (mean dose of <1.5 micrograms per kilogram per week for darbepoetin alfa, or mean dose of <300 Units per kilogram per week for epoetin alfa) for 8 weeks prior to randomization
• Two hemoglobin values between 8.5 and 10.5 grams per deciliter, inclusive, measured at least 4 days apart within 28 days prior to randomization
• Investigator determines the participant is not likely to need rescue therapy (ESA administration or red blood cell transfusion) or require interruption or discontinuation of study drug within the next 30 days
• Serum ferritin ≥100 nanograms per milliliter and transferrin saturation ≥20% within the 28-day screening period prior to randomization
• Folate and vitamin B12 measurements ≥ lower limit of normal within the 28-day screening period prior to randomization
• Hemodialysis adequacy (Kt/Vurea) as indicated by single-pool Kt/Vurea ≥1.2 using the most recent historical measurement within 12 weeks prior to randomization
• Female participants of childbearing potential who are non-lactating, not pregnant as confirmed by a negative serum pregnancy test at Screening within 9 days prior to dosing on Day 1, and using, and agree to continue using, an acceptable method of contraception for at least 4 weeks prior to first dose of study drug until 30 days after the last dose of study drug. Acceptable contraceptive use is outlined in the protocol.
• Female participants of non-childbearing potential who are either surgically sterile (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy) or post-menopausal (>12 months of spontaneous and continuous amenorrhea in a female >55 years old, or >12 months of spontaneous and continuous amenorrhea with a follicle stimulating hormone [FSH] level >40 International Units per Liter in a female <55 years old)
• Female participants of childbearing potential who agree not to donate ova during the study and for at least 30 days after the last dose of study drug
• Male participants who have not had a vasectomy must agree to use an acceptable method of contraception from time of first dose of study drug until 30 days after the last dose of the study drug, and to not donate sperm during the study and for at least 30 days after the last dose of study drug. Acceptable contraceptive use is outlined in the protocol.
• Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

• Treated with any HMG-CoA reductase inhibitor (statin) other than atorvastatin, pravastatin, simvastatin, or rosuvastatin within the 28-day screening period prior to randomization. Within the 28-day screening period prior to randomization, the maximum allowable dose of simvastatin is 20 milligrams (mg) daily, and the maximum allowable dose of rosuvastatin is 10 mg daily. These restrictions also apply to the dosing period.
• Treated with clinically relevant substrates of the breast cancer resistant protein (BCRP) transporter (e.g., sulfasalazine, methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, topotecan, tenofovir, glecaprevir, pibrentasir, or sofosbuvir) within 30 days prior to randomization
• Anemia with a cause other than chronic kidney disease (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
• Active bleeding or blood loss within 8 weeks prior to randomization
• Red blood cell transfusion within 8 weeks prior to randomization
• Anticipated to discontinue hemodialysis or change dialysis modality during the study
• History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin >1.5× upper limit of normal (ULN) within the 28-day screening period prior to randomization. Participants with a history of Gilbert's syndrome may participate in the study if they are not jaundiced, have a total bilirubin <3 × ULN and AST and ALT are not >1.5× ULN.
• Current uncontrolled hypertension that would contraindicate the use of darbepoetin alfa or epoetin alfa as determined by the investigator
• Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular, or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to randomization
• History of new or recurrent malignancy within 2 years prior to Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ may participate on the study.
• History of deep vein thrombosis or pulmonary embolism within 12 weeks prior to randomization
• History of hemosiderosis or hemochromatosis
• History of bilateral native nephrectomy
• History of functioning organ transplantation other than corneal transplant
• Scheduled organ transplant from a living donor or on the kidney transplant wait list or expected to receive a transplant during the study
• History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded)
• Known hypersensitivity to vadadustat excipients, or to darbepoetin alfa or epoetin alfa
• Use of an investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to randomization
• Prior administration of an hypoxia-inducible factor prolyl-hydroxylase, including vadadustat
• Any other reason, which in the opinion of the investigator, would make the participant not suitable for participation in the study
• Treated with probenecid within the 28-day Screening Period prior to randomization or during the study treatment duration