Eligibility Details:
Inclusion Criteria:
- Age: 18 to 99 years of age (inclusive)
- CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5
defined by electronic eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- Erythropoietin-stimulating agents (ESAs)/Hgb: Group 1 (not using ESAs): No ESA use
within the 6 weeks prior to screening and no ESA use between screening and
randomization (Day 1). Group 2 (ESA users): Use of any approved ESA for the 6 weeks
prior to screening and continuing between screening and randomization.
- For Group 1 (not using ESAs), Hgb concentration at Week -8 and Week 1 should be 8 to
10 gram per deciliter (g/dL). For Group 2 (ESA users), Hgb concentration at Week -8
should be 8 to 12 g/dL and at Week 1 should be 8 to 11 g/dL.
- >=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.
Exclusion Criteria:
- Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis
within 90 days after study start (Day 1).
- 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
screening.
- 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
(Day 1).
- 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.
- 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 Q-T 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 darbepoetin 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 to
screening through to randomization (Day 1). At screening, this exclusion applies to
use of the investigational agent within 30 days or within five half lives (whichever
is longer).
- 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 urine 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.
- 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 darbepoetin
alfa) or prevent understanding of the aims or investigational procedures or possible
consequences of the study.
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common.study.methods.is-healthy-yes
