Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
Brief Summary: The primary objective of this study was to evaluate the efficacy of roxadustat compared to darbepoetin alfa in the treatment of anemia in nondialysis-dependent chronic kidney disease (NDD CKD) participants.


Options:
A: 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
B: Inclusion Criteria:

* Chronic kidney disease with an estimated glomerular filtration rate (as calculated by the Japanese GFR estimation equation) of =\<89 mL/min/1.73 m2, and not required dialysis for 3 months since study completion
* The mean of two Hb values at screening test and Hb test (at least one week apart form the screening test) is \<10.0 g/dL, with a difference of ≤1.0 g/dL between the two values
* Both TSAT\>=5% and ferritin \>=30 ng/mL at screening test
* Serum folate ≥4.0 ng/mL and Vitamin B12 ≥180 pg/mL at screening test

Exclusion Criteria:

* Proliferative retinopathy, age-related macular degeneration, retinal vein occlusion and/or macular edema that is considered to require treatment
* Immunological disease with severe inflammation as assessed by the Investigator; even if the inflammation is in remission, the subject is excluded (e.g. lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, celiac disease, etc).
* Having a history of gastric/intestinal resection considered influential on the absorption of the drug in the gastrointestinal tract or evidence of active gastroparesis.
* Uncontrollable hypertension (more than one third blood pressure values of diastolic BP \>100 mmHg within 16 weeks prior to screening test including)
* Congestive heart failure (NYHA classification III or higher)
* Having a history of hospitalization for stroke, myocardial infarction or lung infarction within 24 weeks before screening test
* Positive for any of the following: anti-hepatitis C virus antibody (anti-HCV Ab); hepatitis B surface antigen (HBsAg); or human immunodeficiency virus (HIV)
* Anemia other than anemia due to low/absent renal production of EPO (e.g., iron deficiency anemia, hemolytic anemia, pancytopenia, etc)
* Using ESA, anabolic androgenic steroid, testosterone enanthate or mepitiostane within 6 weeks before screening test
C: Inclusion Criteria:

* Mean of the subjects' two most recent Hb values during the Screening Period must be ≤10.0 g/dL with an absolute difference ≤1.0 g/dL between the two values
* Either transferrin saturation (TSAT) ≥ 5% or serum ferritin ≥ 30 ng/mL during the screening period
* Female subject must either:

Be of non-childbearing potential:

* post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
* documented surgically sterile Or, if of childbearing potential,
* Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
* And have a negative pregnancy test at Screening
* And, if heterosexually active, agree to consistently use two forms of highly effective form of birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and continued for 28 days after the final study drug administration.

  * Female subject must agree not to breastfeed starting at Screening and throughout the study period, and continued for 28 days after the final study drug administration.
  * Female subject must not donate ova starting at Screening and throughout the study period, and continued for 28 days after the final study drug administration.
  * Male subject and their female spouse/partners who are of childbearing potential must be using two forms of highly effective form of birth control (at least one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 12 weeks after the final study drug administration
  * Male subject must not donate sperm starting at Screening and throughout the study period and, for 12 weeks after the final study drug administration

Exclusion Criteria:

* Concurrent retinal neovascular lesion requiring treatment and macular edema requiring treatment
* Concurrent autoimmune disease with inflammation that could impact erythropoiesis
* History of gastric/intestinal resection considered influential on the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent gastroparesis
* Uncontrolled hypertension
* Concurrent congestive heart failure (NYHA Class III or higher)
* History of hospitalization for treatment of stroke, myocardial infarction, or pulmonary embolism within 12 weeks before the screening assessment
* Positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody at the screening assessment, or positive for human immunodeficiency virus (HIV) in a past test
* Concurrent other form of anemia than renal anemia
* Having received treatment with protein anabolic hormone, testosterone enanthate, or mepitiostane within 6 weeks before the screening assessment
* Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or total bilirubin that is greater than the criteria, or previous or concurrent another serious liver disease at screening assessment
* Previous or current malignant tumor (no recurrence for at least 5 years is eligible.)
* Having undergone blood transfusion and/or a surgical procedure considered to promote anemia (excluding shunt reconstruction surgery for access to the blood) within 4 weeks before the screening assessment
* Having undergone a kidney transplantation
* Having a previous history of treatment with ASP1517.
* History of serious drug allergy including anaphylactic shock
* Participation in another clinical study or post-marketing clinical study (including that of a medical device) within 12 weeks before informed consent acquisition
D: Inclusion Criteria:

* Subject has a diagnosis of CKD, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not on dialysis; with an Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m\^2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation.
* The mean of the subject's two most recent (prior to randomization) Hb values during the screening period, obtained at least 4 days apart, must be less than or equal to 10.5 g/dL, with a difference of less than or equal to 1.0 g/dL. The last Hb value must be within 10 days prior to randomization.
* Subject is deemed suitable for treatment with Erythropoiesis Stimulating Agent (ESA) using the criteria specified in the Kidney Disease Improving Global Outcomes (KDIGO) 2012 recommendation considering the rate of fall of Hb concentration, prior response to iron therapy, the risk of needing a transfusion, the risks related to ESA therapy and the presence of symptoms attributable to anemia.
* Subject has a serum folate level greater than or equal to lower limit of normal (LLN) at screening.
* Subject has a serum vitamin B12 level greater than or equal to LLN at screening.
* Subject's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN.
* Subject's body weight is 45.0 kg to a maximum of 160.0 kg.
* Male subject must not donate sperm starting from screening, throughout the study period and up to 12 weeks after final study drug administration.

Exclusion Criteria:

* Subject has received any Erythropoiesis Stimulating Agent (ESA) treatment within 12 weeks prior to randomization.
* Subject has received any dose of IV iron within 6 weeks prior to randomization.
* Subject has received a Red Blood Cell (RBC) transfusion within 8 weeks prior to randomization.
* Subject has a known history of myelodysplastic syndrome or multiple myeloma.
* Subject has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD).
* Subject has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
* Subject has a known chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
* Subject is anticipated to undergo elective surgery that is expected to lead to significant blood loss during the study period or anticipated elective coronary revascularization.
* Subject has active or chronic gastrointestinal bleeding.
* Subject has received any prior treatment with roxadustat or a Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
* Subject has been treated with iron-chelating agents within 4 weeks prior to randomization.
* Subject has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver).
* Subject has known New York Heart Association Class III or IV congestive heart failure.
* Subject has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
* Subject has one or more contraindications for treatment with darbepoetin alfa:

  * Uncontrolled hypertension, or two or more blood pressure values of SBP greater than or equal to 160 mmHg or DBP greater than or equal to 95 mmHg (within 2 weeks prior to randomization).
  * Known hypersensitivity to darbepoetin alfa, recombinant human erythropoietin, or any of the excipients.
* Subject has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma as shown on renal ultrasound within 12 weeks prior to randomization.
* Subject has a history of malignancy, except for the following: cancers determined to be cured or in remission for greater than or equal to 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
* Subject is positive for any of the following:

  * human immunodeficiency virus (HIV).
  * hepatitis B surface antigen (HBsAg).
  * or anti-hepatitis C virus antibody (anti-HCV Ab).
* Subject has an active clinically significant infection that is manifested by White Blood Count (WBC) \> Upper Limit of Normal (ULN), and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization.
* Subject has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion.
* Subject has had any prior organ transplant (that has not been explanted), subject is scheduled for organ transplantation, or subject is likely to initiate renal replacement therapy including dialysis within the first year of the study.
* Subject will be excluded from participation if any of the following apply:

  * subject has received investigational therapy within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to initiation of screening, or
  * any condition which makes the subject unsuitable for study participation.
* Subject has an anticipated use of dapsone in any dose amount or chronic use of acetaminophen/paracetamol \>2.0 g/day during the treatment or follow-up period of the study.
* Subject has a history of alcohol or drug abuse within 2 years prior to randomization

Answer: D