Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Peritoneal Dialysis Subjects With Renal Anemia
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of molidustat in peritoneal dialysis subjects with renal anemia


Options:
A: Inclusion Criteria:

* Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
* Participants who are Stage 3, 4 or 5 CKD defined by estimated Glomerular Filtration Rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
* Hemoglobin as measured by HemoCue at screening visit and Day 1 is \<=11.0 grams/deciliter (g/dL) \[\<=110 gram/Litre (g/L)\].
* Palpable brachial artery as assessed at screening.
* Participants, if necessary may be on stable maintenance oral iron supplementation (\<50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period). If participants have been on intravenous (IV) iron, then participants will not have received IV iron for 4 weeks prior to the Day 1 visit.
* Male or female participants will be included.
* 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 a WOCBP who has been on an approved form of contraceptive for the 4 weeks prior to Day 1 and agrees to follow the contraceptive guidance until the Follow-up visit.
* Capable of giving signed informed consent.

Exclusion Criteria:

* On dialysis or clinical evidence of impending need to initiate dialysis within 12 weeks of Day 1.
* Planned kidney transplant within 12 weeks of Day 1.
* Presence of an arteriovenous (AV) fistula.
* Recombinant human erythropoietin use within the 12 weeks prior to the screening visit and through Day 1.
* History of severe allergic or anaphylactic reactions or hypersensitivity to the study treatment or challenge agents, or excipients in the study treatments or challenge agents.
* Planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until all assessments on Day 42 have been successfully completed.
* The participant has participated in a clinical trial and has received an experimental investigational product within the prior 30 days or within 5 half-lives of the investigational product (whichever is longer) prior to screening and through Day 1.
* At or below the lower limit of the reference range at screening for Vitamin B12 (may rescreen in a minimum of 8 weeks).
* Ferritin \<=50 nanograms/milliliter \[\<=50 microgram/liter (µg/L)\] at screening.
* Transferrin saturation (TSAT) \<=15% (0.15) at screening.
* Folate \<2.0 nanogram/milliliter (4.5 nanomoles/liter; may rescreen in a minimum of 8 weeks) at screening.
* High sensitivity C-reactive protein (hs-CRP) \>=50 micrograms/milliliter (\>=50 mg/L) at screening.
* Myocardial infarction or acute coronary syndrome \<=12 weeks prior to screening and through Day 1.
* Hospitalization for greater than 24 hours \<=12 weeks prior to screening and through Day 1.
* Stroke or transient ischemic attack \<=12 weeks prior to screening and through Day 1.
* Class 4 heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
* Resting SBP \>180 millimeters of mercury (mmHg) or DBP \>110 mmHg at screening visit or current uncontrolled hypertension as determined by the investigator.
* QT interval corrected for heart rate using Bazett's formula (QTcB) \>500 milliseconds (msec), or QTcB \>530 msec in participants with bundle branch block. There is no corrected QT (QTc) exclusion for participants with a predominantly ventricular paced rhythm.
* Active chronic inflammatory disease that could impact erythropoiesis.
* History of bone marrow aplasia or pure red cell aplasia.
* Conditions, other than anemia of CKD, which can affect erythropoiesis.
* Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding from \<=8 weeks prior to screening and through Day 1.
* ALT \>2 times upper limit of normal (ULN; screening only).
* Bilirubin \>1.5 times ULN (screening only); Isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Major surgery within the 12 weeks prior to screening and through Day 1, or planned during the study.
* Anticipated or planned vascular access surgery (i.e., arteriovenous \[AV\] fistula) within the 12 weeks prior to screening and through the Day 42 assessments.
* Received a tissue heart valve replacement or repair within the 6 months prior to screening or has received a mechanical heart valve replacement.
* Blood transfusion within 6 weeks prior to screening and through Day 1, or an anticipated need for blood transfusion during the study.
* Clinical evidence of an acute infection, or history of infection requiring IV antibiotic therapy from 8 weeks prior to screening and through Day 1. Prophylactic oral antibiotics are allowed.
* History of malignancy within the two years prior to screening and through Day 1 or currently receiving treatment for cancer, with the exception of localized squamous cell or basal cell carcinoma of the skin definitively treated 12 weeks prior to Day 1.
* Platelet count \<50,000/µL (\<50 Giga cells per liter).
* History of a bleeding disorder (e.g., hemophilia).
* 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.
B: Inclusion Criteria:

* Male or female subjects ≥ 18 years of age with anemia of chronic kidney disease (CKD) at screening
* Estimated glomerular filtration rate (eGFR) of \< 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease or the formula according to Matsuo, et al.)
* Not on dialysis and not expected to begin dialysis during the treatment period of the study (at least 16 weeks from randomization)
* Treated with darbepoetin via intravenous (IV) or subcutaneous (SC) route with a weekly, bi-weekly, or monthly dose, having had no more than one dose change within 8 weeks prior to randomization
* At least one kidney
* Mean screening hemoglobin (Hb) concentration of 10.0 to 12.0 g/dL
* Men who agree to use adequate contraception when sexually active or women without childbearing potential

Exclusion Criteria:

* Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
* Active hemolysis or diagnosis of hemolytic syndrome
* History of myelodysplastic syndrome, multiple myeloma, marrow fibrosis, or pure red-cell aplasia (PRCA)
* History of hemosiderosis or hemochromatosis
* Hereditary hemoglobinopathies (such as sickle cell disease and thalassemia major)
* Aplastic anemia
* Chronic lymphoproliferative diseases
* Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy that is likely to require invasive treatment (intraocular injections or laser photocoagulation) during the study
* Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
* Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
* Uncontrolled and symptomatic hyperparathyroidism
* Uncontrolled active infection
* Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated \> 3 years prior to randomization
* 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)
C: Inclusion Criteria:

* Patients who diagnosed as a end-stage kidney disease (ESKD) and are receiving stable chronic maintenance dialysis 3 times per week for ≥ 12 weeks
* Patients who are receiving ESA for at least 8 weeks and the dose of ESA is within the dose range of ESA label
* Hb value at screening test is ≥10.0 g/dL
* Receiving hemodialysis via arteriovenous fistula (AVF) or arteriovenous graft (AVG) or via permanent catheter
* Most recent two Hb values before dialysis during washout period must be both \<9.5 g/dL and one of two Hb values must be tested on first visit of the week

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 active gastroparesis
* Uncontrollable hypertension (SBP ≥160 mmHg and DBP ≥110 mmHg, before dialysis, at screening test)
* Congestive heart failure (NYHA classification III or higher)
* Having a history of hospitalization for stroke, myocardial infarction or lung infarction within 24 weeks before 1st registration
* Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab)
* Anemia other than anemia due to low/absent renal production of EPO (e.g., iron deficiency anemia, hemolytic anemia, pancytopenia, etc)
* Pure red cell aplasia
* Using anabolic androgenic steroid, testosterone enanthate or mepitiostane within 6 weeks before 1st registration
D: Inclusion Criteria:

* Subject with end-stage kidney disease (ESKD) on peritoneal dialysis prior to assignment and not expected to start maintenance dialysis (e.g., hemodialysis, hemodiafiltration) other than peritoneal dialysis during the study period
* Body weight \> 40 and ≤ 160 kg at screening
* Male or female subject ≥ 20 years of age at screening
* At least one kidney
* Subjects who meet one of the 1 or 2 following criteria

  * Subjects untreated with ESA at assignment: Mean of the last 2 Hb level (central laboratory measurement) during the screening period must be ≥ 8.0 and \< 11.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment
  * Subjects pre treated with ESA at assignment: Mean of the last 2 Hb level (central laboratory measurement) during the screening period must be ≥ 10.0 and \< 13.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment
* Subjects who meet one of the 1 or 2 following criteria

  * Subjects untreated with ESA at assignment: Subject with ESKD on peritoneal dialysis for at least 2 weeks prior to assignment. AND. Subject not received ESA for 8 weeks prior to assignment. OR. In case of the patient washed out from ESAs, when mean of the last 2 Hb level (at least 2 central laboratory measurements must be taken ≥ 2 days apart) has decrease to ≥ 0.5g/dL from the Hb level (central laboratory measurement) after the last ESA administration, AND the interval from the last ESA administration to the study drug assignment should be over 2 week for epoetin-alpha/beta, 4 weeks for darbepoetin alpha or epoetin beta pegol
  * Subjects pre treated with ESA at assignment:

    * Subject with ESKD on peritoneal dialysis for at least 12 weeks prior to assignment
    * Subject treated with ESA by IV or SC within 8 weeks prior to assignment
    * Treated with 2 or 4 weekly dose of darbepoetin alfa, 4 weekly dose of epoetin beta pegol, OR 3 times per week, twice per week, weekly or bi-weekly dose of epoetin alfa/beta, and having had no more than one dose change within 8 weeks prior to assignment

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≥ 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)

Answer: D