Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
Brief Summary: The purpose of the study is to evaluate the safety and efficacy of roxadustat for treatment of anemia in patients with chronic kidney disease not on dialysis


Options:
A: 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.
B: 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
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
* Currently maintained on erythropoiesis-stimulating agents therapy, with a dose received within 6 weeks prior to or during Screening
* Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States (US) and between 9.0 and 12.0 g/dL (inclusive) outside of the US
* 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 participant with active bleeding or recent blood loss
* Red blood cell transfusion 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:

1. Provision of informed consent prior to any study specific procedures.
2. Age ≥18 years at screening visit 1
3. eGFR \<60 mL/min/1.73 m2, (calculated by central lab) corresponding to stage 3, 4 or 5CKD according to the Kidney Disease Outcomes Quality Initiative (KDOQI), not receiving dialysis
4. Mean of 2 most recent central laboratory Hb values during the screening period, obtained at least 7 days apart, must be \<10.0 g/dL
5. Ferritin ≥50 ng/mL at randomization (obtained from screening visit)
6. TSAT ≥15 % at randomization (obtained from screening visit)
7. Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit)
8. Serum vitamin B12 level ≥LLN at randomization (obtained from screening visit)
9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) and total bilirubin (Tbili) ≤1.5 x ULN at randomization (obtained from screening visit)
10. Body weight 45 to 160 kg

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2. Previous randomization in the present study
3. Any erythropoietin analogue treatment within 6 weeks of randomization
4. New York Heart Association Class III or IV congestive heart failure at enrollment
5. Myocardial infarction (MI), acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization
6. History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto- immune liver disease, cirrhosis or fibrosis of the liver)
7. Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD
8. Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis)
9. Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization
10. Systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg (confirmed by repeated measurement), within 2 weeks prior to randomization. Patients may be rescreened once BP controlled
11. History of prostate cancer, breast cancer or any other malignancy, except 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
12. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)
13. Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia
14. Known hemosiderosis, hemochromatosis or hypercoagulable condition
15. Any prior organ transplant or a scheduled organ transplantation date
16. Any red blood cell transfusion (RBC) during the screening period
17. Any current condition leading to active significant blood loss
18. Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
19. Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of IP in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded)
20. History of alcohol or drug abuse within 2 years prior to randomization
21. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence
22. Pregnant or breastfeeding females
23. Known allergy to the investigational product or any of its ingredients
24. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound efficacy or safety assessment or may interfere with study participation

Answer: D