Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Open-label, Active-controlled, Parallel-group, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Comparison to Darbepoetin Alfa in Non-dialysis Subjects Previously Treated With Erythropoiesis-Stimulating Agents (ESAs)
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of molidustat in non-dialysis subjects previously treated with Erythropoiesis-Stimulating Agents (ESAs)


Options:
A: Inclusion Criteria:

* Subjects with estimated glomerular filtration rate (eGFR)\< 60 mL/min/1.73m\^2 (Chronic kidney disease \[CKD\] stages 3 to 5)
* Have used the same ESA for 8 weeks prior to screening
* Treated with darbepoetin alfa with bi-weekly or monthly dose, epoetin beta pegol with monthly, OR epoetin alfa/beta weekly or bi-weekly, and having had no more than one dose change within 8 weeks prior to randomization
* Body weight \> 40 and ≤ 160 kg at screening
* Male or female subject ≥ 20 years of age at screening
* Not on dialysis and not expected to start dialysis during the study period
* Mean screening Hb level ≥ 10.0 and \< 13.0 g/dL (mean of all central laboratory Hb levels \[at least 2 measurements must be taken ≥ 2 days apart\] during the 8-week screening period, AND all Hb level must be measured by the central laboratory, AND the difference between the lowest level and highest level is \< 1.2 g/dL), with the last screening Hb level measurement within 14 days prior to randomization
* Ferritin ≥ 100 ng/mL or Transferrin saturation ≥ 20%

Exclusion Criteria:

* New York Heart Association (NYHA) Class III or IV congestive heart failure
* History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, pulmonary thromboembolism, and acute limb ischemia) within 6 months prior to randomization
* Sustained and poorly controlled arterial hypertension (defined as systolic BP (blood pressure)≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP \< 90mmHg) at randomization
* Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation)
B: Inclusion Criteria:

* \>=18 years of age at the time of signing the informed consent.
* Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
* Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
* Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
* If needed, participant may be on stable maintenance oral iron supplementation. There should be \<50% change in overall dose and no change in type of iron prescribed in the 4 weeks prior to Day 1 randomization visit.
* Male and female participants are eligible. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
* Capable of giving signed informed consent.

Exclusion Criteria:

* Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
* Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
* Transferrin saturation (TSAT) \<15 percent (Screening only).
* Ferritin \<50 nanograms per milliliter (ng/mL) (Screening only).
* History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
* History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
* History of bone marrow aplasia or pure red cell aplasia (PRCA).
* Participants with Megaloblastic anemia (untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome.
* Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal (GI) bleeding \<= 8 weeks prior to screening through to randomization (Day 1).
* History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
* Use of strong inhibitor of CYP2C8 (for example, gemfibrozil) or strong inducers of CYP2C8 (for example, rifampin/rifampicin).
* Ferric citrate use within 4 weeks prior to randomization (Day 1).
* Use of other investigational agent or device prior to screening through to randomization (Day 1).
* Any prior treatment with daprodustat for a treatment duration of \>30 days.
* MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).
* Stroke or transient ischemic attack within the 8 weeks prior to screening through to randomization. (Day 1).
* Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
* QT interval corrected by Bazett's formula (QTcB) \>500 milliseconds (msec) or QTcB \>530 msec in participants with bundle branch block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
* Alanine transaminase (ALT) \>2x upper limit of normal (ULN) at screening (Week -4).
* Bilirubin \>1.5xULN at screening (Week -4).
* Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
* 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 (for example, Bosniak Category II F, III or IV) \> 3 centimeters (cm).
* Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
* Current uncontrolled hypertension as determined by the investigator.
C: Inclusion Criteria:

* Male and female Japanese participants ≥20 years of age
* Diagnosis of chronic kidney disease (CKD) based on an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m\^2)
* Hemoglobin (Hb) ≤10.5 grams per deciliter (g/dL)
* Not currently being treated with dialysis and not expected to start dialysis within 3 months of screening

Exclusion Criteria:

* Anemia due to a cause other than CKD or presence of active bleeding or recent blood loss
* Sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia
* Red blood cell transfusion within 4 weeks prior to or during screening
* Intravenous iron within 4 weeks prior to or during screening
* Any use of erythropoiesis-stimulating agents within 6 weeks prior to or during screening
D: Inclusion Criteria:

1. Age 18 to 75 years
2. Subject has voluntarily signed and dated an informed consent form
3. Chronic Kidney Disease, not receiving dialysis
4. Hemoglobin (Hb) values in 4 screening visits and the mean Hb must be \<10g/dL
5. Aminotransferase levels (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) and total bilirubin must be ≤ upper limit of normal (ULN) during the screening period
6. Serum alkaline phosphatase (ALP) ≤2x ULN during screening period. Subjects with serum ALP values between 1 x and 2 x ULN may be included only if bone-specific ALP (BSAP) is also elevated \> ULN
7. Total bilirubin values must be ≤ULN during screening period
8. Serum folate and vitamin B12 levels above the lower limit of normal (LLN)
9. Body weight: 40 to 100 kg (dry weight) inclusive
10. Body mass index (BMI): 16 to 38 kg/m2 inclusive

Exclusion Criteria:

1. Received any erythropoiesis-stimulating agent (ESA) other than epoetin alfa within 12 weeks prior to Day 1
2. Any clinically significant infection or evidence of an underlying infection such as a white blood cell count (WBC) \> ULN during screening on two separate occasions,
3. Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); anti-hepatitis C virus antibody (anti-HCV Ab)
4. History of chronic liver disease
5. New York Heart Association Class III or IV congestive heart failure
6. Chronic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
7. Active or chronic gastrointestinal bleeding, or a known coagulation disorder
8. Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.)
9. Hematological disorders, including myelodysplastic syndrome, multiple myeloma, or pure red cell aplasia
10. History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric
11. Active hemolysis or diagnosis of hemolytic syndrome
12. Known bone marrow fibrosis
13. Uncontrolled or symptomatic secondary hyperparathyroidism (PTH\>600ng/L)
14. Any prior organ transplantation
15. Drug-treated gastroparesis, short-bowel syndrome, or any other gastrointestinal condition that may lead to reduced absorption of study drug
16. Serum albumin \<3 g/dL
17. History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the subject
18. Prior treatment with FG-4592
19. Use of an investigational medication or treatment, or carryover effect of an investigational treatment expected, during the screening visit, treatment and follow-up period.
20. Use of traditional Chinese medicines (TCM) during the screening visit to Day 1 or plans to use TCM during the study unless approved in advance by the Medical Monitor

Answer: A