A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Darbepoetin Alfa
The purpose of this multi-center event-driven study in non-dialysis (ND) participants with anemia associated with chronic kidney disease (CKD) is to evaluate the safety and efficacy of daprodustat compared to darbepoetin alfa.
18 Years to 99 Years
Accepting Healthy Volunteers?
- 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.
- 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.