18 Years to 99 Years
Accepting Healthy Volunteers?
- Age: 18 to 99 years of age (inclusive).
- Erythropoietin-stimulating agents (ESAs): Use of any approved ESA for at least the 6
weeks prior to screening and between screening and randomization.
- Hgb concentration: On Week -8: Hgb 8 to 12 grams per deciliter (g/dL). On
randomization (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 of
dialysis 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 with
placebo during run-in period.
- Informed consent (screening only): capable of giving signed informed consent which
includes compliance with the requirements and restrictions listed in the consent form
and in this protocol.
- 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]) at
- 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 cell
disease or myelodysplastic syndrome.
- Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or
esophageal ulcer disease or clinically significant GI bleeding <=4 weeks prior to
screening through to randomization (Day 1).
- MI or acute coronary syndrome: <=4 weeks prior to screening through to randomization
- Stroke or transient ischemic attack: <=4 weeks prior to screening through to
randomization (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 by
the investigator that would contraindicate the use of recombinant human erythropoietin
- 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 for
Heart 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, generally
defined 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 to
randomization (Day 1) or currently receiving treatment for cancer, or complex kidney
cyst (example [e.g.] Bosniak Category II F, III or IV) > 3 centimeter (cm); with the
exception of localized squamous cell or basal cell carcinoma of the skin that has been
definitively treated >=4 weeks prior to screening.
- Severe allergic reactions: History of severe allergic or anaphylactic reactions or
hypersensitivity to excipients in the investigational product, or epoetin alfa or
- 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 to
screening through to randomization (Day 1).
- Prior treatment with daprodustat: Any prior treatment with daprodustat for treatment
duration of >30 days.
- Females only: Subject is pregnant [as confirmed by a positive serum human chorionic
gonadotrophin (hCG) test for females of reproductive potential (FRP) only], subject is
breastfeeding, or subject is of reproductive potential and does not agree to follow
one of the contraceptive options listed in the List of Highly Effective Methods for
- Other Conditions: Any other condition, clinical or laboratory abnormality, or
examination finding that the investigator considers would put the subject at
unacceptable risk, which may affect study compliance (e.g., intolerance to rhEPO) or
prevent understanding of the aims or investigational procedures or possible
consequences of the study.