Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Open-label, Confirmatory Study of MT-6548 Compared to Darbepoetin Alfa in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
Brief Summary: For Non-dialysis subjects with anemia associated with chronic kidney disease, demonstrate non-inferiority of MT-6548 compared to darbepoetin alfa using Hb value and evaluate long-term safety of MT-6548.

For subjects not currently receiving ESAs, evaluate Hb correction and maintenance effect of MT-6548 and for subjects currently receiving ESAs, evaluate Hb conversion and maintenance effect of MT-6548


Options:
A: Inclusion Criteria:

* Diagnosis of CKD
* eGFR \< 60 mL/min/1.73m\^2 during the screening period
* Not receiving dialysis for 8 weeks prior to the screening period, and not expected to start dialysis during the treatment period
* Correction group: Not being treated with ESAs for the recent 8 weeks prior to the screening period
* Conversion group: Being treated with ESAs for the recent 8 weeks prior to the screening period
* Mean of the two screening Hb levels closest in time to the baseline visit. Correction group: ≥8.0 g/dL and \< 11.0 g/dL Conversion group: ≥9.0 g/dL and ≤12.5 g/dL
* Fluctuation between the two Hb levels closest in time to the baseline visit during the screening period less than 1.5 g/dL
* Serum ferritin ≥ 100 ng/mL, or TSAT ≥20% during the screening period
* Folate and vitamin B12 ≥ lower limit of normal during the screening period

Exclusion Criteria:

* Anemia due to a main cause other than CKD: sickle cell disease, myelodysplastic syndrome, bone marrow fibrosis, hematologic malignancy, hemolytic anemia, thalassemia, or pure red cell aplasia
* Active bleeding or recent blood loss within 8 weeks prior to the screening period
* RBC transfusion within 8 weeks prior to the screening period
* Received testosterone enanthate or mepitiostane within 8 weeks prior to the screening period
* AST, ALT, or total bilirubin \>2.5 x upper limit of normal during the screening period
* Uncontrolled hypertension (diastolic blood pressure \>110 mm Hg or systolic blood pressure \>180 mm Hg) during the screening period and Day 1
* Ophthalmic examinations during the screening period correspond to either of the following criteria;

  * No available fundal findings
  * Findings indicating the presence of active fundal disease
* Severe heart failure (New York Heart Association Class IV)
* Cerebrovascular disorder or acute coronary syndrome (hospitalization due to unstable angina or myocardial infarction), requiring hospitalization due to urgent percutaneous intervention for coronary or heart failure within 12 weeks prior to the screening period
* Current or history of malignancy. History of malignancy with no recurrence for the recent 5 years is not an exclusion criterion
* New onset or recurrent event of deep vein thrombosis or pulmonary embolism within 12 weeks prior to the screening period
* Current or history of hemosiderosis or hemochromatosis
* History of prior organ transplantation or scheduled organ transplant, or prior transplantation of hematopoietic stem cell or bone marrow
* Males and females of childbearing potential who are unwilling to use an acceptable method of contraception during the designated period (Males: during the study and 90 days after the last dose, females: during study and 30 days after the last dose)
* Females who are pregnant or breast feeding, or are predicted to be pregnant
B: Inclusion Criteria:

1. Ability to understand and give informed consent for participation. 2. Hemoglobin values during the screening period must be 8-11 g/dL (both inclusive).

3.

1. Patients will be considered not treated with erythropoietin analogue (Epoetin and Darbepoeitin) if they have not received erythropoietin analogue for at least 4 weeks and Mircera® for at least 8 weeks prior to screening visit. OR
2. Patients who are on ESA therapy must be on stable dose for 4 weeks prior to enrollment (≤30% of dose change).

   4. Patients on hemodialysis (≥2 times in a week) for at least 12 weeks prior to screening visit and have access consisting of an arteriovenous fistula, AV graft, or catheter (permanent/temporary).

   5. Patients with no planned change in dialysis modality and with no planned renal transplant during study period.

   6. Left ventricular ejection fraction ≥40% by echocardiogram prior to randomization.

   7. No iron, folate or Vitamin B12 deficiency.

   8. 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. Red blood cell transfusion within 8 weeks prior to participating in the study.
   2. History of previous or concurrent cancer.
   3. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection.
   4. Active infection at initiation of study.
   5. History of renal transplant.
   6. Uncontrolled hypertension (defined as SBP \>180 mmHg or DBP \>100 mmHg) at screening visit (before dialysis).
   7. Patient on high rhEPO dose at screening visit. \[High dose defined as an epoetin dose of ≥450 IU/kg/week intravenous or ≥ 300 IU/kg/week subcutaneous or darbepoetin dose of ≥1.5 µg/kg/week subcutaneous\].
   8. 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.
   9. Unable to swallow tablets or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; malabsorption syndrome, resection of the small bowel or poorly controlled inflammatory bowel disease affecting the small intestine.
   10. History of uncontrolled autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP) or thalassemia.
   11. 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.
   12. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
   13. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Desidustat or Epoetin alfa or to any erythropoieisis-stimulating agent.
   14. Pregnant and breastfeeding women.
   15. Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety.
   16. Other laboratory abnormalities that, in the opinion of the investigator, would compromise the patient's safety or interfere with data interpretation.
   17. Presence of other clinically significant 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.
   18. 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).
   19. History of difficulty with donating blood.
   20. History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening.
   21. Participants who have participated in any drug research study other than the present trial within past 3 months.
   22. 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 entry in the study.
   23. Existing clinically active chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease)
   24. In case of DM patients, HbA1c \>9%.
   25. Female volunteers with following criteria will not be recruited:

       * History of pregnancy or lactation in the past 3 months
       * Fertile female volunteers not protected against pregnancy by adequate long- term anti-fertility measures
       * History of less than 1 year of menopause and not using adequate long-term anti-fertility measures
       * Positive urine pregnancy test at Visit 2
       * Positive serum β-hCG level at the screening visit
   26. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or history of myocardial infarction prior to first dose with study drug.
C: 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
D: Inclusion Criteria:

* Diagnosis of CKD
* Receiving hemodialysis or hemodiafiltration 3 times a week for more than 12 weeks prior to the screening period, excluding receiving home dialysis or combination of peritoneal dialysis.
* Being treated with ESAs for the recent 8 weeks prior to the screening period
* Mean of the two screening Hb levels closest in time to the baseline visit is ≥9.5 g/dL and ≤12.0 g/dL
* Fluctuation between the two Hb levels closest in time to the baseline visit during the screening period less than 1.5 g/dL
* Serum ferritin ≥ 100 ng/mL, or TSAT ≥20% during the screening period
* Folate and vitamin B12 ≥ lower limit of normal during the screening period

Exclusion Criteria:

* Anemia due to a main cause other than CKD: sickle cell disease, myelodysplastic syndrome, bone marrow fibrosis, hematologic malignancy, hemolytic anemia, thalassemia, or pure red cell aplasia
* Active bleeding or recent blood loss within 8 weeks prior to the screening period
* RBC transfusion within 8 weeks prior to the screening period
* Received testosterone enanthate or mepitiostane within 8 weeks prior to the screening period
* AST, ALT, or total bilirubin \>2.5 x upper limit of normal during the screening period
* Uncontrolled hypertension (diastolic blood pressure \>110 mm Hg or systolic blood pressure \>180 mm Hg) at the first day of the screening period and Day 1
* Ophthalmic examinations during the screening period correspond to either of the following criteria;

  * No available fundal findings
  * Findings indicating the presence of active fundal disease
* Severe heart failure (New York Heart Association Class IV)
* Cerebrovascular disorder or acute coronary syndrome (hospitalization due to unstable angina or myocardial infarction), requiring hospitalization due to urgent percutaneous intervention for coronary or heart failure within 12 weeks prior to the screening period
* Current or history of malignancy. History of malignancy with no recurrence for the recent 5 years is not an exclusion criterion
* New onset or recurrent event of deep vein thrombosis or pulmonary embolism within 12 weeks prior to the screening period
* Current or history of hemosiderosis or hemochromatosis
* History of prior organ transplantation or scheduled organ transplant, or prior transplantation of hematopoietic stem cell or bone marrow
* Males and females of childbearing potential who are unwilling to use an acceptable method of contraception during the designated period (Males: during the study and 90 days after the last dose, females: during study and 30 days after the last dose)
* Females who are pregnant or breast feeding, or are predicted to be pregnant

Answer: A