Study of Roxadustat (FG-4592) in Participants With End-Stage Renal Disease Receiving Maintenance Hemodialysis

• Sponsor: FibroGen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01147666
• Collaborator: AstraZeneca (Industry), Astellas Pharma Inc (Industry)
• Enrollment: 161
• Locations: 25
• Arms: 15
• Actual Duration (Months): 29
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy and safety of roxadustat in participants with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy, previously treated with intravenous (IV) epoetin alfa.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease; Anemia	Drug: Roxadustat; Drug: Epoetin Alfa; Other: Placebo	Phase 2

Detailed Description

Dose ranging study with consecutive cohorts in two participant populations: participants normally responding to current anemia treatment (epoetin alfa) ("normoresponders": participants with baseline epoetin alfa dose at study entry 75 to 450 international units [IU]/kilograms [kg]/week) and participants not responding well to current treatment ("hyporesponders": participants with maintenance epoetin alfa dose above 450 IU/kg/week). Normoresponders are randomized to study drug roxadustat or epoetin alfa at a ratio of 3:1; hyporesponders are randomized to study drug roxadustat or epoetin alfa or placebo at a ratio of 2:1:1. The study objectives are to demonstrate that roxadustat is effective in maintaining hemoglobin (Hb) levels when converting from epoetin alfa and to establish optimum starting doses and dose adjustment regimens for Hb maintenance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) and Single-Blind Placebo-Controlled, Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis
• Actual Study Start Date: May 17, 2010
• Actual Primary Completion Date: Oct 15, 2012
• Actual Study Completion Date: Oct 15, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A-1 (Roxadustat 1.0 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.0 milligrams (mg)/kg, administered orally 3 times weekly (TIW) in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 grams [g]/deciliter [dL]) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-2 (Roxadustat 1.5 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-3 (Roxadustat 2.0 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-4 (Roxadustat 1.8 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who have not completed 6-week treatment at the time of Amendment 2, will continue treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-5 (Roxadustat 1.8 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-6 (Roxadustat 1.3 mg/kg TIW) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-9 (Roxadustat 2.0 mg/kg) Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg) Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) will receive tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants will receive roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Active Comparator: Cohorts A (Epoetin Alfa) Normoresponsive participants will receive IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing will occur on dialysis days in each Cohort A. Dose adjustment will be per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Drug: Epoetin Alfa; Epoetin Alfa will be administered per dose and schedule specified in the arms.
Experimental: Cohort B-1 (Roxadustat 1.5 mg/kg TIW) Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Experimental: Cohort B-2 (Roxadustat 2.0 mg/kg TIW) Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) will receive roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who have not completed 6-week treatment at the time of Amendment 2, will continue treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) will be based upon regular monitoring of Hb.	Drug: Roxadustat; Roxadustat will be administered per dose and schedule specified in the arms.; Other Names: FG-4592
Active Comparator: Cohort B (Epoetin Alfa) Hyporesponsive participants will receive IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing will occur on dialysis days in each Cohort B. Dose adjustment will be per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Drug: Epoetin Alfa; Epoetin Alfa will be administered per dose and schedule specified in the arms.
Placebo Comparator: Cohort B (Placebo) Hyporesponsive participants will receive placebo matched to roxadustat, administered orally TIW for 19 weeks.	Other: Placebo; Placebo matching to roxadustat will be administered per schedule specified in the arm.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only [Week 7]

   Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values.

2. Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks [Week 7]

   Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

3. Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks [Weeks 17, 18, 19, and 20]

   The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

Secondary Outcome Measures

1. Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) [Weeks 17, 18, 19, and 20]

   The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.

2. Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks) [Weeks 17, 18, 19, and 20]

   The average of the mean Hb values that were within 10-13 g/dL at Weeks 17, 18, 19, and 20 are presented. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. LOCF method was used to impute missing values.

3. Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks [Baseline, Week 7]

   Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

4. Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks [Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20]

   Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.

5. Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only [Baseline up to Week 6]

   Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

6. Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks [Baseline up to Week 19]

   Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

7. Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks [Week 7]

8. Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks [Week 7]

9. Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level [Week 7]

   Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

10. Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level [Weeks 8, 10, 12, 14, 17, 19, and 20]

    Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

11. Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks [Baseline up to Week 6]

    Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

12. Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks [Baseline up to Week 19]

    Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.

13. Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks [Baseline up to Week 6]

14. Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks [Baseline up to Week 19]

15. Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6 [Baseline up to Week 6]

    The rate of rise was computed as the slope of the regression line of change in Hb level (in g/dL) vs. time (in weeks) using Random Coefficient Model. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.

16. Trough Plasma Concentration of Roxadustat and Epoetin Alfa [Predose, 4, 8, 12, 24, 48, and 72 hours postdose at Weeks 1 and 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• ESRD and receiving maintenance HD TIW for ≥4 months prior to Day 1

• Two most recent Hb values obtained during screening period must be within the ranges set below:

1. Group A. Normoresponder Criteria: Hb range in the 8 weeks prior to randomization within 9.0 to 13.5 g/dL ii) Group B. Hyporesponder Criteria: Hb range in the 8 weeks prior to randomization within 8.5 to 13.5 g/dL

• Epoetin alfa, dose requirements:

1. Group A. Normoresponder Criteria - Cohorts A-1 to A-12: Stable IV epoetin alfa dose at baseline (that is, no more than a 30% fluctuation in the weekly dose) during the 4 weeks prior to study Day -3

1. Cohorts A-1 to A-4: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 85 IU/kg/dose, TIW; weekly dose between 75 and 255 IU/kg/week

2. Cohort A-5: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 115 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week

3. Cohort A-9: Current and previous (past 4 weeks) epoetin alfa dose range ≥85 to 150 IU/kg/dose, TIW; total weekly dose between 255 and 450 IU/kg/week

4. Cohorts A-6 to A-8: Current and previous (past 4 weeks) epoetin alfa dose range 25 to 115 IU/kg/dose, TIW, and two times a week (BIW); total weekly dose between 75 and 345 IU/kg/week

5. Cohorts A-10 to A-12: Optional cohorts to be decided (TBD), dosing frequency and dose range to be determined by sponsor ii) Group B. Hyporesponder Criteria:

6. Cohort B-1 (completed): Current and previous (past 4 weeks) epoetin alfa dose range 125 to 400 IU/kg/dose, TIW; weekly dose between 375 and 1200 IU/kg/week

7. Cohort B-2 to B-4: Current and previous (past 4 weeks) epoetin alfa dose range

115 IU/kg/dose, TIW; total weekly dose >345 IU/kg/week no requirement for stability of epoetin alfa doses

• Complete Blood Count (CBC), Hematology, liver function blood tests, serum folate and vitamin B12 within acceptable limits

• Absence of active or chronic gastrointestinal bleeding

• High sensitivity C-reactive protein (hsCRP) <60 mg/liter for normoresponders Cohorts A-8 through A-12 enrolled under Amendment 3; no hsCRP criteria for hyporesponders

• Body weight: 40 to 140 kg (dry weight)

• Body mass index (BMI): 18 to 45 kg/meter square (m^2)

• Dialysis vascular access via native arteriovenous fistula or synthetic graft, or permanent (tunneled) catheter (not via temporary catheter); permanent and temporary catheters, however, are still prohibited in Cohort A-5

Key Exclusion Criteria:

• Anticipated change in HD prescription

• Any clinically significant infection or evidence of an underlying infection

• Positive for any of the following: Human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab)

• History of chronic liver disease

• New York Heart Association Class III or IV congestive heart failure

• Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission

• History of myelodysplastic syndrome

• History of hemosiderosis, hemochromatosis, polycystic kidney disease, or anephric

• Active hemolysis or diagnosis of hemolytic syndrome

• Known bone marrow fibrosis

• Uncontrolled or symptomatic secondary hyperparathyroidism

• Any prior organ transplantation

• Drug-treated gastroparesis or short-bowel syndrome

• History of alcohol or drug abuse; or a positive drug screen for a substance that has not been prescribed for the participant

• Prior treatment with roxadustat

• Diagnosis or suspicion of renal cell carcinoma

• Red blood cell (RBC) transfusion within 12 weeks prior to Day 1, or anticipated need for RBC transfusion during the dosing period

• IV iron supplement within 2 weeks prior to Day 1 and/or unwilling to withhold IV iron during the dosing/treatment period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tempe	Arizona	United States
2		Pine Bluff	Arkansas	United States
3		Azusa	California	United States
4		Los Angeles	California	United States
5		Northridge	California	United States
6		Ontario	California	United States
7		Paramount	California	United States
8		Yuba City	California	United States
9		Miami	Florida	United States
10		Pembroke Pines	Florida	United States
11		Honolulu	Hawaii	United States
12		Louisville	Kentucky	United States
13		Detroit	Michigan	United States
14		Kansas City	Missouri	United States
15		Paterson	New Jersey	United States
16		New York	New York	United States
17		Rosedale	New York	United States
18		Williamsville	New York	United States
19		Toledo	Ohio	United States
20		Orangeburg	South Carolina	United States
21		Arlington	Texas	United States
22		Fort Worth	Texas	United States
23		Houston	Texas	United States
24		San Antonio	Texas	United States
25		Fairfax	Virginia	United States

Sponsors and Collaborators

• FibroGen
• AstraZeneca
• Astellas Pharma Inc

Investigators

• Study Director: Marietta Franco, FibroGen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: FibroGen
• ClinicalTrials.gov Identifier: NCT01147666
• Other Study ID Numbers: FGCL-4592-040
• First Posted: Jun 22, 2010
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by FibroGen: Kidney; End Stage Renal Disease; ESRD; Chronic Kidney Disease; CKD; Renal; Anemia; Oral anemia treatment; Hemoglobin levels; Blood count; Erythropoietin; Hemodialysis; Normoresponder; Hyporesponder
• Additional relevant MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Anemia; Epoetin Alfa

Study Results

Participant Flow

Pre-assignment Detail

Normoresponder participants were enrolled sequentially in 10 cohorts (A-1 to A-10) with the exception of Cohort A-5 in parallel enrollment with A-6 to A-8. Hyporesponder participants were enrolled in 2 cohorts (B-1 and B-2). Normoresponder participants were those with stable baseline epoetin alfa doses between 75 and 450 international units (IU)/kilogram (kg)/week, while hyporeponders required maintenance epoetin alfa dose above 450 IU/kg/week.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 milligrams (mg)/kg, administered orally 3 times weekly (TIW) in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target hemoglobin (Hb) values (11.0-13.0 grams [g]/deciliter [dL]) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received intravenous (IV) epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Period Title: Dosing Period 1: 6-Week Treatment
STARTED	12	12	12	12	12	12	12	12	2	10	36	4	5	4	4
Received at Least 1 Dose of Study Drug	12	12	12	12	12	12	12	12	2	10	36	4	5	4	4
Efficacy Evaluable (EE) Population	9	10	9	11	11	11	11	10	2	10	31	1	3	4	3
COMPLETED	10	10	11	10	7	9	9	9	2	8	33	2	1	3	0
NOT COMPLETED	2	2	1	2	5	3	3	3	0	2	3	2	4	1	4
Period Title: Dosing Period 1: 6-Week Treatment
STARTED	0	0	0	7	12	12	12	12	2	10	23	0	5	3	3
Received at Least 1 Dose of Study Drug	0	0	0	7	12	12	12	12	2	10	23	0	5	3	3
EE Population for 19-week Treatment	0	0	0	6	11	11	11	10	2	10	22	0	3	3	2
COMPLETED	0	0	0	5	7	9	9	9	2	8	21	0	1	2	0
NOT COMPLETED	0	0	0	2	5	3	3	3	0	2	2	0	4	1	3

Baseline Characteristics

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)	Total
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.	Total of all reporting groups
Overall Participants	12	12	12	12	12	12	12	12	2	10	36	4	5	4	4	161
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.1 (12.1)	58.8 (13.6)	56.6 (10.8)	50.8 (19.4)	55.2 (10.6)	58.7 (10.1)	61.9 (11.9)	55.7 (14.5)	57.0 (17.0)	55.8 (6.8)	57.9 (11.0)	55.0 (8.8)	60.2 (5.9)	47.0 (12.5)	58.8 (8.6)	56.3 (3.680644)
Sex: Female, Male (Count of Participants)
Female	4 33.3%	1 8.3%	7 58.3%	5 41.7%	4 33.3%	2 16.7%	5 41.7%	4 33.3%	1 50%	3 30%	13 36.1%	3 75%	5 100%	2 50%	2 50%	61 37.9%
Male	8 66.7%	11 91.7%	5 41.7%	7 58.3%	8 66.7%	10 83.3%	7 58.3%	8 66.7%	1 50%	7 70%	23 63.9%	1 25%	0 0%	2 50%	2 50%	100 62.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Normoresponder Participants Treated for 6 Weeks Only
Description	Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. Last observation carried forward (LOCF) method was used to impute missing values.
Time Frame	Week 7

Outcome Measure Data

Analysis Population Description

EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (erythropoiesis-stimulating agent [ESA], IV Iron or red blood cell [RBC] transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy. Here, 'Overall number of participants analyzed' signifies normoresponder participants who were treated for 6 weeks only.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	9	10	9	5	9
Count of Participants [Participants]	4 33.3%	8 66.7%	7 58.3%	4 33.3%	3 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A-1 (Roxadustat 1.0 mg/kg TIW), Cohort A (Epoetin Alfa)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	Threshold for significance at 0.05 level.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cohort A-2 (Roxadustat 1.5 mg/kg TIW), Cohort A (Epoetin Alfa)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0698
	Comments	Threshold for significance at 0.05 level.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cohort A-3 (Roxadustat 2.0 mg/kg TIW), Cohort A (Epoetin Alfa)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1534
	Comments	Threshold for significance at 0.05 level.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Cohort A-4 (Roxadustat 1.8 mg/kg TIW), Cohort A (Epoetin Alfa)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2657
	Comments	Threshold for significance at 0.05 level.
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Number of Participants With Week 7 Hb ≥ Baseline Hb - 0.5 g/dL, Among Hyporesponsive Participants Treated for at Least 6 Weeks
Description	Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.
Time Frame	Week 7

Outcome Measure Data

Analysis Population Description

EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy.

Arm/Group Title	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 6 weeks.
Measure Participants	1	3	4	3
Count of Participants [Participants]	0 0%	1 8.3%	2 16.7%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A-2 (Roxadustat 1.5 mg/kg TIW), Cohort A-4 (Roxadustat 1.8 mg/kg TIW)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	Threshold for significance at 0.05 level.
	Method	Fisher Exact
	Comments

3. Primary Outcome

Title	Number of Participants With a Mean Hb Above 11 g/dL When the Mean Hb Values at Weeks 17, 18, 19, and 20 Were Averaged, Among Participants Treated for 19 Weeks
Description	The average of the mean Hb values that were above 11 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.
Time Frame	Weeks 17, 18, 19, and 20

Outcome Measure Data

Analysis Population Description

EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	6	11	11	11	10	2	10	22	3	3	2
Count of Participants [Participants]	4 33.3%	4 33.3%	6 50%	5 41.7%	6 50%	2 16.7%	4 33.3%	8 66.7%	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants With a Mean of Hb Within 11-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)
Description	The average of the mean Hb values that were within 11-13 g/dL at Weeks 17, 18, 19, and 20 are presented. LOCF method was used to impute missing values.
Time Frame	Weeks 17, 18, 19, and 20

Outcome Measure Data

Analysis Population Description

EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	6	11	11	11	10	2	10	22	3	3	2
Count of Participants [Participants]	4 33.3%	1 8.3%	6 50%	5 41.7%	6 50%	2 16.7%	3 25%	8 66.7%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With a Mean of Hb Within 10-13 g/dL (Values Obtained at Weeks 17, 18, 19, and 20 for Participants Dosed for 19 Weeks)
Description	The average of the mean Hb values that were within 10-13 g/dL at Weeks 17, 18, 19, and 20 are presented. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants. LOCF method was used to impute missing values.
Time Frame	Weeks 17, 18, 19, and 20

Outcome Measure Data

Analysis Population Description

EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	6	11	11	11	10	2	10	22
Count of Participants [Participants]	5 41.7%	2 16.7%	10 83.3%	10 83.3%	7 58.3%	2 16.7%	6 50%	19 158.3%

6. Secondary Outcome

Title	Change From Baseline in Hb at Week 7 for Participants Treated for at Least 6 Weeks
Description	Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.
Time Frame	Baseline, Week 7

Outcome Measure Data

Analysis Population Description

EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 6 weeks.
Measure Participants	9	10	9	11	11	11	11	10	2	10	31	1	3	4	3
Mean (Standard Deviation) [g/dL]	-0.40 (1.56)	0.91 (1.59)	0.71 (1.61)	0.25 (1.86)	-0.15 (1.36)	-0.18 (1.55)	-0.32 (1.39)	-0.47 (0.94)	-0.00 (2.12)	0.24 (1.82)	-0.51 (1.31)	-2.63	-0.89 (0.74)	-0.28 (0.81)	-2.50 (0.23)

7. Secondary Outcome

Title	Change From Baseline in Hb at Weeks 8, 10, 12, 14, 17, 19, and 20 for Participants Treated for 7-19 Weeks
Description	Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values.
Time Frame	Baseline, Weeks 8, 10, 12, 14, 17, 19, and 20

Outcome Measure Data

Analysis Population Description

EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	6	11	11	11	10	2	10	22	3	3	2
Change at Week 8	0.49 (1.31)	0.08 (1.56)	0.01 (1.51)	-0.49 (1.49)	-0.29 (1.09)	0.05 (2.05)	0.20 (1.85)	-0.21 (1.02)	-0.89 (0.99)	-0.41 (1.52)	-2.37 (0.00)
Change at Week 10	0.56 (1.49)	0.17 (1.65)	-0.17 (1.32)	-0.56 (1.35)	-0.27 (1.22)	-0.15 (0.07)	0.26 (2.07)	-0.34 (1.19)	-1.46 (1.41)	0.19 (1.48)	-2.37 (0.00)
Change at Week 12	0.26 (1.49)	0.04 (1.57)	-0.10 (1.42)	-0.56 (1.44)	-0.35 (1.17)	-0.15 (0.92)	0.38 (2.28)	-0.48 (1.20)	-2.02 (1.47)	-0.08 (2.50)	-2.37 (0.00)
Change at Week 14	0.53 (1.55)	-0.03 (1.73)	-0.27 (1.29)	-0.41 (1.44)	-0.24 (1.68)	-0.15 (1.77)	0.33 (2.37)	-0.50 (1.23)	-2.29 (1.71)	0.42 (1.83)	-2.37 (0.00)
Change at Week 17	-0.09 (0.88)	-0.09 (1.96)	-0.27 (1.07)	-0.48 (1.42)	-0.27 (1.18)	-0.30 (0.85)	0.02 (2.06)	-0.45 (1.57)	-2.69 (1.61)	0.16 (2.27)	-2.37 (0.00)
Change at Week 19	-0.11 (1.18)	-0.32 (1.84)	-0.28 (1.07)	-0.82 (1.19)	-0.35 (1.20)	0.05 (0.07)	-0.10 (2.03)	-0.30 (1.43)	-3.02 (1.08)	0.12 (2.27)	-2.37 (0.00)
Change at Week 20	-0.39 (1.16)	-0.55 (1.88)	-0.55 (1.24)	-0.82 (1.27)	-0.33 (1.34)	0.15 (0.07)	-0.57 (1.68)	-0.36 (1.50)	-2.82 (1.19)	0.12 (2.14)	-2.47 (0.14)

8. Secondary Outcome

Title	Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 6 Weeks Only
Description	Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time Frame	Baseline up to Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were randomized and received at least one dose of study medication. Here, 'Overall number of participants analyzed' signifies participants who were treated for 6 weeks only.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	12	12	12	5	13
Dose Increased	0 0%	3 25%	0 0%	0 0%	9 75%
Dose Reduced	0 0%	0 0%	0 0%	2 16.7%	6 50%
Dose Interrupted	4 33.3%	7 58.3%	4 33.3%	0 0%	3 25%
Dose Resume	0 0%	6 50%	4 33.3%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants Who Required Dose Adjustments During the Dosing Period for Participants Treated for 19 Weeks
Description	Number of participants who required dose increase, dose reduce, dose interruption or dose resume were reported. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time Frame	Baseline up to Week 19

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were randomized and received at least one dose of study medication.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	7	12	12	12	12	2	10	23
Dose Increased	2 16.7%	5 41.7%	5 41.7%	4 33.3%	7 58.3%	1 8.3%	8 66.7%	12 100%
Dose Reduced	3 25%	3 25%	5 41.7%	4 33.3%	4 33.3%	1 8.3%	6 50%	11 91.7%
Dose Interrupted	1 8.3%	5 41.7%	2 16.7%	0 0%	1 8.3%	0 0%	3 25%	9 75%
Dose Resume	0 0%	3 25%	1 8.3%	0 0%	1 8.3%	0 0%	1 8.3%	8 66.7%

10. Secondary Outcome

Title	Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for At Least 6 Weeks
Time Frame	Week 7

Outcome Measure Data

Analysis Population Description

EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 6 weeks.
Measure Participants	9	10	9	11	11	11	11	10	2	10	31	1	3	4	3
Count of Participants [Participants]	3 25%	3 25%	5 41.7%	5 41.7%	4 33.3%	3 25%	6 50%	6 50%	0 0%	1 10%	19 52.8%	0 0%	2 40%	3 75%	0 0%

11. Secondary Outcome

Title	Number of Participants Whose Hb Levels Were Maintained at Week 7 to Within ±1 g/dL of Their Mean 4-Week Screening Period Baseline Value for Participants Treated for 19 Weeks
Time Frame	Week 7

Outcome Measure Data

Analysis Population Description

EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	6	11	11	11	10	2	10	22	3	3	2
Count of Participants [Participants]	3 25%	4 33.3%	3 25%	6 50%	6 50%	0 0%	1 8.3%	13 108.3%	2 100%	3 30%	0 0%

12. Secondary Outcome

Title	Number of Participants Treated for 6 Weeks Only Whose Hb Levels at Week 7 Were Greater Than Their Baseline Level
Description	Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time Frame	Week 7

Outcome Measure Data

Analysis Population Description

EE population included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy. Here, 'Overall number of participants analyzed' signifies participants who were treated for 6 weeks only.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	9	10	9	5	9
Count of Participants [Participants]	3 25%	7 58.3%	6 50%	3 25%	2 16.7%

13. Secondary Outcome

Title	Number of Participants Treated for 7-19 Weeks Whose Hb Levels at Weeks 8, 10, 12, 14, 17, 19, and 20 Were Greater Than Their Baseline Level
Description	Baseline was defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment, including Day 1 predose. LOCF method was used to impute missing values. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time Frame	Weeks 8, 10, 12, 14, 17, 19, and 20

Outcome Measure Data

Analysis Population Description

EE population for 19 weeks treatment included all participants randomized designated to receive 19 weeks of study medication and had received study treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion), or who permanently discontinued study medication during the dosing period due to lack of efficacy.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-125 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-125 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-125 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	6	11	11	11	10	2	10	22
Week 8	3 25%	6 50%	4 33.3%	4 33.3%	4 33.3%	1 8.3%	6 50%	9 75%
Week 10	3 25%	6 50%	4 33.3%	4 33.3%	5 41.7%	0 0%	6 50%	7 58.3%
Week 12	3 25%	6 50%	6 50%	4 33.3%	3 25%	1 8.3%	5 41.7%	9 75%
Week 14	3 25%	6 50%	6 50%	4 33.3%	1 8.3%	1 8.3%	6 50%	6 50%
Week 17	2 16.7%	5 41.7%	5 41.7%	4 33.3%	4 33.3%	1 8.3%	6 50%	6 50%
Week 19	2 16.7%	4 33.3%	5 41.7%	2 16.7%	4 33.3%	1 8.3%	6 50%	8 66.7%
Week 20	3 25%	3 25%	5 41.7%	2 16.7%	5 41.7%	2 16.7%	5 41.7%	7 58.3%

14. Secondary Outcome

Title	Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for at Least 6 Weeks
Description	Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.
Time Frame	Baseline up to Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were randomized and received at least one dose of study medication.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 6 weeks.
Measure Participants	12	12	12	12	12	12	12	12	2	10	36	4	5	4	4
Count of Participants [Participants]	2 16.7%	2 16.7%	3 25%	4 33.3%	2 16.7%	3 25%	2 16.7%	3 25%	0 0%	4 40%	6 16.7%	1 25%	3 60%	0 0%	1 25%

15. Secondary Outcome

Title	Number of Participants Who Required Rescue Anemia Treatment Due to Hb Levels, Among Participants Treated for 19-Weeks
Description	Rescue anemia treatment included any ESA dosing, RBC transfusion, or IV iron.
Time Frame	Baseline up to Week 19

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were randomized and received at least one dose of study medication.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	7	12	12	12	12	2	10	23	5	3	3
Count of Participants [Participants]	4 33.3%	2 16.7%	3 25%	2 16.7%	3 25%	0 0%	4 33.3%	4 33.3%	3 150%	0 0%	1 2.8%

16. Secondary Outcome

Title	Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for at Least 6-Weeks
Time Frame	Baseline up to Week 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were randomized and received at least one dose of study medication.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring o	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 6 weeks.
Measure Participants	12	12	12	12	12	12	12	12	2	10	36	4	5	4	4
Count of Participants [Participants]	0 0%	0 0%	0 0%	1 8.3%	0 0%	2 16.7%	1 8.3%	2 16.7%	1 50%	4 40%	6 16.7%	0 0%	0 0%	1 25%	0 0%

17. Secondary Outcome

Title	Number of Participants Requiring Dose Reduction Secondary to Excessive Erythropoiesis During Dosing Period, Among Participants Treated for 19-Weeks
Time Frame	Baseline up to Week 19

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were randomized and received at least one dose of study medication.

Arm/Group Title	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	7	12	12	12	12	2	10	23	5	3	3
Count of Participants [Participants]	0 0%	0 0%	2 16.7%	1 8.3%	2 16.7%	1 8.3%	4 33.3%	6 50%	0 0%	1 10%	0 0%

18. Secondary Outcome

Title	Rate of Change in Hb Levels, Measured by Regression Slopes of the Hb Values During Treatment up to Week 6
Description	The rate of rise was computed as the slope of the regression line of change in Hb level (in g/dL) vs. time (in weeks) using Random Coefficient Model. Because of the small number of hyporesponders enrolled into this study, data for this secondary efficacy analysis as planned per protocol was not collected and summarized for hyporesponder participants.
Time Frame	Baseline up to Week 6

Outcome Measure Data

Analysis Population Description

EE included participants who received treatment for at least 4 weeks with corresponding Hb measurements not resulted from any rescue therapies including inadvertent use of rescue medication (ESA, IV Iron or RBC transfusion) or who permanently discontinued study drug during dosing period due to lack of efficacy. Here, 'Overall number of participants analyzed' signifies participants who were treated for 6 weeks only.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A (Epoetin Alfa)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.
Measure Participants	9	10	9	5	9
Number [g/dL/week]	-0.0135	0.1926	0.1682	-0.0220	-0.1267

19. Secondary Outcome

Title	Trough Plasma Concentration of Roxadustat and Epoetin Alfa
Time Frame	Predose, 4, 8, 12, 24, 48, and 72 hours postdose at Weeks 1 and 6

Outcome Measure Data

Analysis Population Description

Data for trough plasma concentration of roxadustat and epoetin alfa were not collected for this study.

Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)	Cohort A-2 (Roxadustat 1.5 mg/kg TIW)	Cohort A-3 (Roxadustat 2.0 mg/kg TIW)	Cohort A-4 (Roxadustat 1.8 mg/kg TIW)	Cohort A-5 (Roxadustat 1.8 mg/kg TIW)	Cohort A-6 (Roxadustat 1.3 mg/kg TIW)	Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)	Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)	Cohort A-9 (Roxadustat 2.0 mg/kg)	Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)	Cohorts A (Epoetin Alfa)	Cohort B-1 (Roxadustat 1.5 mg/kg TIW)	Cohort B-2 (Roxadustat 2.0 mg/kg TIW)	Cohort B (Epoetin Alfa)	Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.	Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.	Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Adverse Events

Time Frame	Baseline up to Week 23
Adverse Event Reporting Description	Safety population included all participants who were randomized and received at least one dose of study medication.
Arm/Group Title	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)		Cohort A-2 (Roxadustat 1.5 mg/kg TIW)		Cohort A-3 (Roxadustat 2.0 mg/kg TIW)		Cohort A-4 (Roxadustat 1.8 mg/kg TIW)		Cohort A-5 (Roxadustat 1.8 mg/kg TIW)		Cohort A-6 (Roxadustat 1.3 mg/kg TIW)		Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)		Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)		Cohort A-9 (Roxadustat 2.0 mg/kg)		Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)		Cohorts A (Epoetin Alfa)		Cohort B-1 (Roxadustat 1.5 mg/kg TIW)		Cohort B-2 (Roxadustat 2.0 mg/kg TIW)		Cohort B (Epoetin Alfa)		Cohort B (Placebo)
Arm/Group Description	Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.0 mg/kg, administered orally TIW in the morning of the day after dialysis (interdialytic days) for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-85 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 85-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.8 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.3 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.3 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 100 mg, and 150 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 85-150 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants (with baseline epoetin alfa dosage 25-115 IU/kg/dose at study entry) received tiered, weight-based initial doses of roxadustat (approximately 1.5 mg/kg/dose TIW). Low weight (40 to 60 kg), medium weight (>60 to 90 kg), and heavy weight (>90 to 140 kg) participants received roxadustat 70 mg, 120 mg, and 200 mg, respectively, administered as oral capsules for 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Normoresponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort A. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.		Hyporesponsive participants (with baseline epoetin alfa dosage 125-400 IU/kg/dose at study entry) received roxadustat capsules at a dose of 1.5 mg/kg, administered orally TIW for 6 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Hyporesponsive participants (with baseline epoetin alfa dosage >115 IU/kg/dose at study entry) received roxadustat capsules at a dose of 2.0 mg/kg, administered orally TIW for 6 weeks. Participants who had not completed 6-week treatment at the time of Amendment 2, continued treatment for up to 19 weeks. Dose adjustment to achieve correction and subsequent maintenance of target Hb values (11.0-13.0 g/dL) was based upon regular monitoring of Hb.		Hyporesponsive participants received IV epoetin alfa treatments on Day 1, at their prestudy dose and according to their prestudy dosing schedule (TIW). Epoetin alfa dosing occurred on dialysis days in each Cohort B. Dose adjustment was per local standard of care (exclusive of IV iron) for routine maintenance of stable Hb levels on dialysis participants.		Hyporesponsive participants received placebo matched to roxadustat, administered orally TIW for 19 weeks.
All Cause Mortality
	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)		Cohort A-2 (Roxadustat 1.5 mg/kg TIW)		Cohort A-3 (Roxadustat 2.0 mg/kg TIW)		Cohort A-4 (Roxadustat 1.8 mg/kg TIW)		Cohort A-5 (Roxadustat 1.8 mg/kg TIW)		Cohort A-6 (Roxadustat 1.3 mg/kg TIW)		Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)		Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)		Cohort A-9 (Roxadustat 2.0 mg/kg)		Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)		Cohorts A (Epoetin Alfa)		Cohort B-1 (Roxadustat 1.5 mg/kg TIW)		Cohort B-2 (Roxadustat 2.0 mg/kg TIW)		Cohort B (Epoetin Alfa)		Cohort B (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)		Cohort A-2 (Roxadustat 1.5 mg/kg TIW)		Cohort A-3 (Roxadustat 2.0 mg/kg TIW)		Cohort A-4 (Roxadustat 1.8 mg/kg TIW)		Cohort A-5 (Roxadustat 1.8 mg/kg TIW)		Cohort A-6 (Roxadustat 1.3 mg/kg TIW)		Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)		Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)		Cohort A-9 (Roxadustat 2.0 mg/kg)		Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)		Cohorts A (Epoetin Alfa)		Cohort B-1 (Roxadustat 1.5 mg/kg TIW)		Cohort B-2 (Roxadustat 2.0 mg/kg TIW)		Cohort B (Epoetin Alfa)		Cohort B (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		3/12 (25%)		0/12 (0%)		4/12 (33.3%)		5/12 (41.7%)		3/12 (25%)		5/12 (41.7%)		3/12 (25%)		0/2 (0%)		3/10 (30%)		6/36 (16.7%)		2/4 (50%)		2/5 (40%)		1/4 (25%)		0/4 (0%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Cardiac disorders
Cardiac failure congestive	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Acute myocardial infarction	0/12 (0%)		2/12 (16.7%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Cardiac arrest	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Cardio-respiratory arrest	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Coronary artery disease	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Myocardial infarction	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Gastrointestinal disorders
Diverticular perforation	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		1/4 (25%)		0/4 (0%)
Gastrointestinal haemorrhage	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Nausea	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Pancreatitis acute	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Retroperitoneal haemorrhage	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Vomiting	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
General disorders
Non-cardiac chest pain	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Sudden cardiac death	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Immune system disorders
Hypersensitivity	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Infections and infestations
Cellulitis	0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Gangrene	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Gastroenteritis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Pneumonia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Bacteraemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Diabetic gangrene	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Endocarditis bacterial	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Infection	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Sepsis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula site haemorrhage	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Vascular graft complication	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Vascular pseudoaneurysm ruptured	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Fluid overload	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Hyperkalaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		2/36 (5.6%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Diabetes mellitus inadequate control	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Diabetic ketoacidosis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Hyperglycaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Hypocalcaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		1/10 (10%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Hypokalaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		1/10 (10%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Nervous system disorders
Cerebrovascular accident	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		1/10 (10%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Complex partial seizures	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Haemorrhagic stroke	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Psychiatric disorders
Major depression	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary	0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Dyspnoea	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Pulmonary oedema	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Subcutaneous emphysema	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		1/10 (10%)		0/36 (0%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Vascular disorders
Peripheral vascular disorder	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		1/36 (2.8%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Cohort A-1 (Roxadustat 1.0 mg/kg TIW)		Cohort A-2 (Roxadustat 1.5 mg/kg TIW)		Cohort A-3 (Roxadustat 2.0 mg/kg TIW)		Cohort A-4 (Roxadustat 1.8 mg/kg TIW)		Cohort A-5 (Roxadustat 1.8 mg/kg TIW)		Cohort A-6 (Roxadustat 1.3 mg/kg TIW)		Cohort A-7 (Weight Tiered Roxadustat 70-100-150 mg)		Cohort A-8 (Weight Tiered Roxadustat 70-120-200 mg)		Cohort A-9 (Roxadustat 2.0 mg/kg)		Cohort A-10 (Weight Tiered Roxadustat 70-120-200 mg)		Cohorts A (Epoetin Alfa)		Cohort B-1 (Roxadustat 1.5 mg/kg TIW)		Cohort B-2 (Roxadustat 2.0 mg/kg TIW)		Cohort B (Epoetin Alfa)		Cohort B (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		1/12 (8.3%)		1/12 (8.3%)		4/12 (33.3%)		2/12 (16.7%)		2/12 (16.7%)		1/12 (8.3%)		2/12 (16.7%)		0/2 (0%)		3/10 (30%)		2/36 (5.6%)		3/4 (75%)		2/5 (40%)		0/4 (0%)		1/4 (25%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/12 (0%)		0/12 (0%)		2/12 (16.7%)		0/12 (0%)		0/12 (0%)		1/12 (8.3%)		0/12 (0%)		0/2 (0%)		2/10 (20%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		1/4 (25%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)		1/12 (8.3%)		0/12 (0%)		2/12 (16.7%)		2/12 (16.7%)		2/12 (16.7%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		2/36 (5.6%)		0/4 (0%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Vomiting	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Nausea	3/12 (25%)		0/12 (0%)		1/12 (8.3%)		1/12 (8.3%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		2/12 (16.7%)		0/2 (0%)		1/10 (10%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
General disorders
Fatigue	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Catheter site pain	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Infections and infestations
Cellulitis	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Otitis Externa	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Upper respiratory tract infection	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Post procedural swelling	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Investigations
Haemoglobin decreased	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Nervous system disorders
Headache	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Syncope	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Wheezing	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Sinus congestion	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		0/4 (0%)		1/5 (20%)		0/4 (0%)		0/4 (0%)
Ingrowing nail	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/2 (0%)		0/10 (0%)		0/36 (0%)		1/4 (25%)		0/5 (0%)		0/4 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.