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 Maintenance Treatment of Anemia in End Stage Renal Disease Patients on Stable Dialysis
Brief Summary: This study was conducted to explore a new therapy for anemia in participants with end stage renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment of anemia.


Options:
A: Inclusion Criteria:

Main Inclusion:

* Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to randomization.
* Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks prior to randomization with stable weekly doses (during 4 weeks prior to randomization).
* Mean of the participant's three most recent Hb values, as measured by central laboratory, during the Screening Period.
* Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN

Exclusion Criteria:

Main Exclusion:

* Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to randomization.
* Participant 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).
* Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
* Participant has had uncontrolled hypertension, in the opinion of the investigator, within 2 weeks prior to randomization.
* Participant has a history of malignancy, except for the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
* Participant has had any prior organ transplant (that has not been explanted), or participant is scheduled for organ transplantation.
B: Inclusion Criteria

* More than or equal to 40 years of age, at the time of signing the informed consent
* Stable Hgb 8.5 to 11.5 grams per deciliter (g/dL) inclusive.
* Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three-to five-times weekly for at least 4 weeks prior to screening.
* A single pool Kt/Vurea \>=1.2 based on a historical value obtained within 3 months prior to screening in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio should be at least 65 percent (%).
* Treated with an ESA (epoetins or their biosimilars, darbepoetin, or methoxy polyethylene glycol \[PEG\]-epoetin beta) for at least 4 weeks prior to screening.
* Participants may be on stable (\<=50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period) maintenance oral or intravenous (IV; \<=100 mg/week) iron supplementation. If participants are on oral or IV iron, then doses must be stable for the 4 weeks prior to Washout.
* Weight: Mid-week weight change between dialysis treatments \<5% as assessed post-dialysis at the Screening and Washout visits.
* On at least 1 antihypertensive medication (excluding diuretics) and on that same medication and the same dose for at least 1 week prior to Washout.
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and the protocol.
* Willing and able to wear ABPM device for at least 25 hours on two separate sessions.

Exclusion Criteria

* Planned change from HD to peritoneal dialysis within the study time period, or on home dialysis.
* Planned for kidney transplant within the 16 weeks following the Screening visit.
* An epoetin alfa dose of \>=360 U/kg/week IV or \>=250 U/kg/week subcutaneous (SC), or darbepoetin dose of \>=1.8 micrograms (μg)/kg/week IV or SC, or methoxy PEG-epoetin beta dose of \>=2.2 μg/kg/week within the 8 weeks prior to screening through Week -4.
* Planned or recorded administration of Mircera (methoxy PEG-epoetin beta) within the 4 weeks prior to the Washout.
* Occurrence of myocardial infarction or acute coronary syndrome within 3 months prior to Washout.
* Stroke or transient ischemic attack within 3 months prior to Washout.
* Chronic Class 4 heart failure, as defined by the New York Heart Association functional classification system diagnosed prior to Washout.
* 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 QTc exclusion for participants with a predominantly paced rhythm.
* Resting post dialysis SBP \>160 millimeters of mercury (mmHg); or DBP \>100 mmHg at screening or uncontrolled hypertension as determined by the investigator.
* Presence of atrial fibrillation.
* Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) diagnosed prior to Washout.
* History of bone marrow aplasia or pure red cell aplasia.
* Other causes of anemia including Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.
* Alanine transaminase (ALT) \>2 times upper limit of normal (ULN) (screening only) or Bilirubin \>1.5 times ULN (screening only) or 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.
* Major surgery (excluding vascular access surgery) within the 3 months prior to Washout or planned during the study.
* Blood transfusion within the 8 weeks prior to Washout or an anticipated need for blood transfusion during the study.
* Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding within the 8 weeks prior to Washout.
* Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 8 weeks prior to Washout.
* History of malignancy within the two years prior to screening through Day 1 or currently receiving treatment for cancer, or has a known complex kidney cyst (e.g., Bosniak Category IIF, III or IV) \>=3 centimeters.
* Participants with an upper arm diameter which cannot be measured by oscillometer/ sphygmomanometer cuff or for whom BP cannot be measured in the opposite arm of current vascular access.
* History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
* Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until Washout.
* The participant has participated in a clinical trial and has received an experimental investigational product within the 30 days prior to Day 1 or within 5 half lives of the investigational product prior to screening, whichever is longer.
* 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.
* A female participant is pregnant (as confirmed by a positive serum human chorionic gonadotrophin test for females of reproductive potential only), participant is breastfeeding, or participant is of reproductive potential and does not agree to follow one of the pre-specified contraceptive options
* Vitamin B12 at or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks, following treatment).
* Folate at \<2.0 nanograms/milliliter (ng/mL) (4.5 Nanomoles per Liter) (may rescreen in a minimum of 4 weeks, following treatment).
* Ferritin at \<100 ng/mL
* Transferrin saturation at \<20%.
C: 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)
D: Inclusion criteria:

* Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving 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 Participant's three most recent Hb values during the Screening period, obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a difference of less than or equal to 1.0 g/dL between the highest and the lowest values. The last Hb value must be within 10 days prior to randomization.
* Participant has a ferritin level greater than or equal to 30 ng/mL (greater than or equal to 67.4 pmol/L) at screening.
* Participant has a transferrin saturation (TSAT) level greater than or equal to 5% at screening.
* Participant has a serum folate level greater than or equal to lower limit of normal at screening.
* Participant has a serum vitamin B12 level greater than or equal to lower limit of normal at screening.
* Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels 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.
* Participant's body weight is 45.0 kg up to a maximum of 160.0 kg.

Exclusion criteria:

* Participant has received any ESA treatment within 12 weeks prior to randomization.
* Participant has had more than one dose of IV iron within 12 weeks prior to randomization.
* Participant has received a RBC transfusion within 8 weeks prior to randomization.
* Participant has a known history of myelodysplastic syndrome or multiple myeloma.
* Participant 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 CKD.
* Participant has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
* Participant has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
* Participant is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization.
* Participant has active or chronic gastrointestinal bleeding.
* Participant has received any prior treatment with roxadustat or a hypoxia-inducible factor Prolyl Hydroxylase Inhibitor (HIF-PHI).
* Participant has been treated with iron-chelating agents within 4 weeks prior to randomization.
* Participant has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver)
* Participant has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure.
* Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization.
* Uncontrolled hypertension or two or more blood pressure (BP) values of systolic BP (SBP) greater than or equal to 160 mmHg or diastolic BP (DBP) greater than or equal to 95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization.
* Participant has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma on renal ultrasound within 12 weeks prior to randomization.
* Participant has a history of malignancy, except 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.
* Participant 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).
* Participant has an active clinically significant infection manifested by White Blood Count (WBC) \> ULN, and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization.
* Participant has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration and retinal vein occlusion.
* Participant has had any prior organ transplant (that has not been explanted) or a scheduled organ transplantation.
* Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to the initiation of Screening.
* Participant 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.
* Participant has a history of alcohol or drug abuse within 2 years prior to randomization.

Answer: A