Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE - CORRECTION/CONVERSION)
Brief Summary: A multicenter, randomized, open-label, active-controlled Phase 3 study for the correction or maintenance treatment of anemia in participants with incident dialysis-dependent chronic kidney disease (DD-CKD).


Options:
A: Inclusion Criteria:

* - Eligible subjects will have a diagnosis of anemia associated with CKD(chronic kidney disease).
* Women without childbearing potential
* Male or female subject ≥ 18 years of age with anemia of CKD at screening
* On dialysis, defined as regular long-term hemodialysis, with the same modality of dialysis for ≥ 3 months before randomization
* Dialysis vascular access via native arteriovenous fistula, synthetic graft, long-term catheters, or long-term tunneled catheters
* Treated with epoetin alfa (US or Japan) or epoetin beta (Japan) via intravenous (IV) or subcutaneous (SC) route, on stable dosing defined as a \< 50% change from the maximum prescribed weekly dose with no change in the prescribed frequency during the last 8 weeks prior to randomization
* At least one kidney
* Mean screening Hb concentration 9.0 to 11.5 g/dL inclusive (mean of all local laboratory Hb measurements \[at least 2 measurements must be taken ≥ 2 days apart\] during the 4 week screening period, AND none of the measurements can be \< 9.0 g/dL or \> 12.0 g /dL
* Serum ferritin levels ≥ 100 μg/L OR transferrin saturation ≥ 20% at screening. Iron substitution is allowed
* Folate and vitamin B12 levels above the lower limit of normal. Supplementation is allowed
* Exclusion Criteria:
* Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
* Hereditary hemoglobinopathies (including, but not limited to, sickle cell disease, beta thalassemia, and thalassemia major) which may be the primary cause of anemia
* Chronic lymphoproliferative diseases
* Any allograft (including renal allograft) in place and on immunosuppressive therapy, or a scheduled kidney transplant within the next 16 weeks (being on a waiting list does not exclude the subject)
* Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease)
* Subjects treated with immuno- or myelosuppressive therapy within 8 weeks prior to randomization: e.g., everolimus, sirolimus, rituximab, azathioprine, mycophenolate mofetil, mycophenolic acid, cyclosporine,methotrexate, and tacrolimus, chemotherapeutic agents and other anticancer agents, and systemic steroids (except inhaled steroids) for 7 days
* RBC-containing transfusion within 8 weeks before randomization
* History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the last 6 months from the initial screening visit
* Sustained, poorly controlled arterial hypertension or hypotension at screening, defined as a mean BP ≥ 180/110 mmHg or systolic BP \< 95 mmHg, respectively
* Severe rhythm or conduction disorder (e.g., HR \< 50 or \> 110 bpm, atrial flutter, prolonged QT \>500 msec, second or third degree atrioventricular \[AV\]block if not treated with a pacemaker)
* New York Heart Association Class III or IV congestive heart failure
* Severe hepatic insufficiency (defined as alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], or gamma-glutamyl transferase \> 3 times the upper limit of normal \[ULN\], total bilirubin \> 2 mg/dL, or Child-Pugh B or C) or active hepatitis in the investigator's opinion
* A scheduled surgery that may be expected to lead to significant blood loss
B: Inclusion Criteria:

* ≥18 years of age
* Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) at Screening and not expected to start dialysis within 6 months of Screening
* Mean Screening hemoglobin \<10.0 grams per deciliter (g/dL)
* Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

Exclusion Criteria:

* Anemia due to a cause other than CKD or participants with active bleeding or recent blood loss
* Red blood cell transfusion within 8 weeks prior to randomization.
* Any erythropoietic stimulating agent within 8 weeks prior to randomization
* Uncontrolled hypertension
* Severe heart failure at Screening (New York Heart Association Class IV)
* 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, or stroke within 12 weeks prior to or during Screening
* Hypersensitivity to Darbepoetin or Vadadustat or to any of their excipients
C: Inclusion Criteria:

* ≥18 years of age
* Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening
* Mean Screening hemoglobin between 8.0 and \<11.0 grams per deciliter (g/dL) (inclusive)
* Serum ferritin ≥100 nanograms per deciliter (ng/mL) and TSAT ≥20% during Screening

Exclusion Criteria:

* Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
* Red blood cells transfusion within 8 weeks prior to randomization
* Anticipated to recover adequate kidney function to no longer require dialysis
* Uncontrolled hypertension
* Severe heart failure at Screening (New York Heart Association Class IV)
* Acute coronary syndrome (hospitalization for unstable angina, 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 congestive heart failure; or stroke within 12 weeks prior to or during Screening.
* Participants meeting the criteria of erythropoiesis-stimulating agent resistance within 8 weeks prior to or during Screening defined as follows

  1. epoetin: \> 7700 units/dose three times per week or \>23,000 units per week
  2. Darbepoetin alfa: \>100 micrograms per week (mcg/week)
  3. methoxy polyethylene glycol-epoetin beta: \>100 micrograms (mcg) every other week or \>200 mcg/month
* Hypersensitivity to Vadadustat, Darbepoetin alfa or any of their excipients
D: Inclusion Criteria:

1. Current clinical diagnosis of anemia due to CKD, baseline hemoglobin concentrations must be 7.0-10.0 g/dL (both inclusive) before the enrollment.
2. Ability to understand and give informed consent for participation.
3. Male or female patients diagnosed with CKD (stage III to V, not receiving dialysis) defined by estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
4. Male or female, 18 to 80 years of age.
5. Body weight \> 40 kg.
6. Subjects not on dialysis and not expected to start dialysis during the study period.
7. Patients must not be treated with erythropoiesis-stimulating agent (ESA) therapy within 6 weeks prior to enrollment.
8. Estimated GFR ≥10 mL/min/1.73 m2.
9. Serum ferritin ≥100 ng/mL and/or Transferrin Saturation \>20%.
10. No iron, folate or Vitamin B12 deficiency.
11. Females of childbearing potential, must agree to use one of the approved contraception methods, from screening until completion of the follow-up visit.

Exclusion Criteria:

1. Prior chronic hemodialysis or chronic peritoneal dialysis treatment.
2. Intravenous iron within 14 days prior to enrollment.
3. Prior exposure of rhEPO analogues less than 04 weeks.
4. Red blood cell transfusion within 8 weeks prior to enrollment.
5. History of previous or concurrent cancer.
6. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection.
7. Active infection prior to enrollment.
8. History of renal transplant.
9. Major surgery within 90 days of the first day of study drug dosing, and minor surgery within 30 days of the first day of study drug dosing.
10. Unable to swallow tablets or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; mal-absorption syndrome, resection of the small bowel or poorly controlled inflammatory bowel disease affecting the small intestine.
11. History of uncontrolled autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP) or thalassemia.
12. Presence or a history of bleeding disorders or clinical conditions (e.g. gastrointestinal \[GI\] bleeding or constitutional disorders) that may increase risk of life-threatening bleeding.
13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
14. History of severe allergic or hypersensitivity to investigational products and its excipients.
15. Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists or other medications within 28 days of the first dose of study drug that in the investigator's opinion, could compromise patient safety.
16. Pregnant and breastfeeding women.
17. Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety.
18. Other laboratory abnormalities that, in the opinion of the investigator, would compromise the patient's safety or interfere with data interpretation.
19. Presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement) which, in the Investigator's opinion, could compromise the patient's safety.
20. History of significant alcoholism or drug abuse within the past 1 year. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day).
21. History of difficulty with donating blood.
22. History or presence of any clinically significant ECG abnormalities during screening.
23. Participants who have participated in any drug research study other than the present trial within past 3 months.
24. Participants who have donated one unit (350 ml) of blood in the past 3 months or history of whole blood transfusion in last 120 days prior to enrollment.
25. History of chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease, Systemic Lupus Erythematosus \[SLE\]).
26. In case of Diabetes mellitus patients, glycosylated haemoglobin (HbA1c) \>9 %.

Answer: C