Phase III Study of GSK1278863 in Japanese Non-dialysis (ND) and Peritoneal Dialysis (PD) Subjects With Renal Anemia

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02791763
• Collaborator: (none)
• Enrollment: 355
• Locations: 56
• Arms: 3
• Actual Duration (Months): 28.6
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase III, open-label, active-controlled, parallel-group, multi-center study to compare the efficacy and safety of GSK1278863 administered for 52 weeks versus epoetin beta pegol in approximately 286 Japanese ND and 50 PD subjects with renal anemia. The study will consist of three cohorts. Cohort 1 and Cohort 3 will consist of ND subjects (Erythropoiesis-Stimulating Agent [ESA] users and ESA non-users) randomized to receive GSK1278863 or epoetin beta pegol in a ratio of 1:1. PD subjects will be enrolled into Cohort 2 and will receive GSK1278863. This study consists of a 4-week screening phase, a 52-week treatment phase (including primary efficacy evaluation period [Weeks 40 to 52]), and a 4-week follow-up phase following the treatment phase. The primary objective of this study is to demonstrate non-inferiority of GSK1278863 to epoetin beta pegol based on mean hemoglobin (Hgb) during the primary efficacy evaluation period in ND subjects. ESA non-users from Cohort 1 will be excluded from the primary efficacy analysis. Study results will be used as pivotal study data for an NDA submitted for GSK1278863 for the treatment of renal anemia in Japan.

Condition or Disease	Intervention/Treatment	Phase
Anaemia	Drug: 1 to 4 mg tablets of GSK1278863; Drug: 6 mg GSK1278863 tablet; Drug: Epoetin beta pegol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-week, Phase III, Open-label, Multi-center Study to Evaluate Efficacy and Safety of GSK1278863 in Japanese Non-dialysis and Peritoneal Dialysis Subjects With Anemia Associated With Chronic Kidney Disease
• Actual Study Start Date: Jun 6, 2016
• Actual Primary Completion Date: Oct 26, 2018
• Actual Study Completion Date: Oct 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daprodustat in ND participants Eligible ND participants will receive oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Drug: 1 to 4 mg tablets of GSK1278863; 7.0 millimeters (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of GSK1278863 as active ingredient, to be orally administered once daily.; Drug: 6 mg GSK1278863 tablet; 9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of GSK1278863 as active ingredient, to be orally administered once daily.
Active Comparator: Epoetin beta pegol in ND participants Eligible ND participants will receive subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.	Drug: Epoetin beta pegol; An injectable formulation containing 25 micrograms µg, 50 µg, 75 µg, 100 µg, 150 µg, 200 µg, or 250 µg of epoetin beta pegol per syringe (0.3 mL), supplied as a glass syringe prefilled with epoetin beta pegol solution (clear colorless to pale yellow). Epoetin beta pegol will be subcutaneously administered once every 2 or 4 weeks.
Experimental: Daprodustat in PD participants Eligible PD participants will receive oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.	Drug: 1 to 4 mg tablets of GSK1278863; 7.0 millimeters (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of GSK1278863 as active ingredient, to be orally administered once daily.; Drug: 6 mg GSK1278863 tablet; 9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of GSK1278863 as active ingredient, to be orally administered once daily.

Outcome Measures

Primary Outcome Measures

1. Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants [Weeks 40 to 52]

   The mean hemoglobin during the primary efficacy evaluation period in ND participants was estimated by a statistical model using Mixed Model Repeated Measures (MMRM).

Secondary Outcome Measures

1. Number of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) [Weeks 40 to 52]

   ND participants with observed mean Hgb within the target range during the primary efficacy evaluation period were summarized. Responders were defined as the participants with the mean Hgb within target range during the primary efficacy evaluation period.

2. Percentage of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) [Weeks 40 to 52]

   The percentage of ND participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Responders were defined as the participants with the mean Hgb within target range during the primary efficacy evaluation period.

3. Change From Baseline in Hgb at Week 4 in ND Participants [Baseline (Day 1) and Week 4]

   Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb at Week 4 in ND participants is presented.

4. Change From Baseline in Hgb at Week 4 in PD Participants [Baseline (Day 1) and Week 4]

   Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb at week 4 in PD participants is presented.

5. Number of ND Participants by Hgb Change From Baseline Category at Week 4 [Baseline (Day 1) and Week 4]

   Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.

6. Percentage of ND Participants by Hgb Change From Baseline Category at Week 4 [Baseline (Day 1) and Week 4]

   Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.

7. Number of PD Participants by Hgb Change From Baseline Category at Week 4 [Baseline (Day 1) and Week 4]

   Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.

8. Percentage of PD Participants by Hgb Change From Baseline Category at Week 4 [Baseline (Day 1) and Week 4]

   Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.

9. Daprodustat Dose Level by Visit in ND Participants [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48]

   Daprodustat dose level at each assessment visit for ND participants is presented using 25th percentile (P25), median, and 75th percentile (P75).

10. Epoetin Beta Pegol Dose Level by Visit in ND Participants [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48]

    Dose of epoetin beta pegol at a scheduled visit was converted to dose per 4 weeks when the dose frequency was every 2 weeks. Epoetin beta pegol dose level at each assessment visit for ND participants is presented using 25th percentile (P25), median, and 75th percentile (P75).

11. Daprodustat Dose Level by Visit in PD Participants [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48]

    Daprodustat dose level at each assessment visit for PD participants is presented using 25th percentile (P25), median, and 75th percentile (P75).

12. Duration of Treatment Interruption Due to Hgb >13 g/dL in ND Participants [Up to Week 52]

    The duration (in days) of treatment interruption due to Hgb >13 g/dL per participant was summarized descriptively on participants with a period of treatment interruption due to Hgb >13 g/dL.

13. Duration of Treatment Interruption Due to Hgb >13 g/dL in PD Participants [Up to Week 52]

    The duration (in days) of treatment interruption due to Hgb >13 g/dL per participant was summarized descriptively on participants with a period of treatment interruption due to Hgb >13 g/dL.

14. Number of Dose Adjustments in ND Participants [Up to Week 52]

    Number of dose adjustments in ND participants is presented.

15. Number of Dose Adjustments in PD Participants [Up to Week 52]

    Number of dose adjustments in PD participants is presented.

16. Hgb Values at Each Assessment Visit in ND Participants [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Hgb values at each assessment visit for ND participants is presented.

17. Hgb Values at Each Assessment Visit in PD Participants [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Hgb values at each assessment visit for PD participants is presented.

18. Change From Baseline in Hgb Values at Each Assessment Visit in ND Participants [Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb values at each assessment visit in ND participants is presented.

19. Change From Baseline in Hgb Values at Each Assessment Visit in PD Participants [Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb values at each assessment visit in PD participants is presented.

20. Number of ND Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Number of ND participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.

21. Percentage of ND Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Percentage of ND participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.

22. Number of PD Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Number of PD participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.

23. Percentage of PD Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit [Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

    Percentage of PD participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.

24. Percentage of Time With Hgb Within the Target Range (11.0 to 13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants [Weeks 40 to 52]

    Mean percentage of time with Hgb within the target range (11.0 to 13.0 g/dL) is summarized during the primary efficacy evaluation period (Weeks 40 to 52).

25. Percentage of Time With Hgb Within the Target Range (11.0 to 13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in PD Participants [Weeks 40 to 52]

    Mean percentage of time with Hgb within the target range (11.0 to 13.0 g/dL) is summarized during the primary efficacy evaluation period (Weeks 40 to 52).

26. Time to Reach the Lower Target Hgb Level (11.0 g/dL) in ND Participants [Up to week 52]

    The time (in days) to reach the lower target Hgb level (11.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. Participants who did not reach the lower Hgb target were considered as censored cases. Participants who were randomized as Hgb >= 11.0 g/dL were excluded in this summary.

27. Time to Reach the Lower Target Hgb Level (11.0 g/dL) in PD Participants [Up to week 52]

    The time (in days) to reach the lower target Hgb level (11.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. Participants who did not reach the lower Hgb target were considered as censored cases. Participants who were randomized as Hgb >= 11.0 g/dL were excluded in this summary.

28. Number of ND Participants Who Had an Hgb Level of Less Than 7.5 g/dL [Up to week 52]

    Number of ND participants who had an Hgb level of less than 7.5 g/dL is presented.

29. Percentage of ND Participants Who Had an Hgb Level of Less Than 7.5 g/dL [Up to week 52]

    Percentage of ND participants who had an Hgb level of less than 7.5 g/dL is presented.

30. Number of PD Participants Who Had an Hgb Level of Less Than 7.5 g/dL [Up to week 52]

    Number of PD participants who had an Hgb level of less than 7.5 g/dL is presented.

31. Percentage of PD Participants Who Had an Hgb Level of Less Than 7.5 g/dL [Up to week 52]

    Percentage of PD participants who had an Hgb level of less than 7.5 g/dL is presented.

32. Number of ND Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks [Up to week 52]

    Number of ND participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.

33. Percentage of ND Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks [Up to week 52]

    Percentage of ND participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.

34. Number of PD Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks [Up to week 52]

    Number of PD participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.

35. Percentage of PD Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks [Up to week 52]

    Percentage of PD participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.

36. Number of ND Participants Who Had an Hgb Level of More Than 13.0 g/dL [Up to week 52]

    Number of ND participants who had an Hgb level of more than 13.0 g/dL is presented.

37. Percentage of ND Participants Who Had an Hgb Level of More Than 13.0 g/dL [Up to week 52]

    Percentage of ND participants who had an Hgb level of more than 13.0 g/dL is presented.

38. Number of PD Participants Who Had an Hgb Level of More Than 13.0 g/dL [Up to week 52]

    Number of PD participants who had an Hgb level of more than 13.0 g/dL is presented.

39. Percentage of PD Participants Who Had an Hgb Level of More Than 13.0 g/dL [Up to week 52]

    Percentage of PD participants who had an Hgb level of more than 13.0 g/dL is presented.

40. Number of Episodes With Hgb Level of More Than 13.0 g/dL in ND Participants [Up to week 52]

    Number of episodes with Hgb level of more than 13.0 g/dL in ND participants is presented.

41. Number of Episodes With Hgb Level of More Than 13.0 g/dL in PD Participants [Up to week 52]

    Number of episodes with Hgb level of more than 13.0 g/dL in PD participants is presented.

42. Monthly Average Dose of Oral Iron During the Treatment Period in ND Participants [Up to Week 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron = Total oral iron dose (mg) / (duration in days / 30.4375 days). Monthly average dose of oral iron during the treatment period in ND participants is presented.

43. Monthly Average Dose of Oral Iron During the Treatment Period in PD Participants [Up to Week 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron = Total oral iron dose (mg) / (duration in days / 30.4375 days). Monthly average dose of oral iron during the treatment period in PD participants is presented.

44. Monthly Average Dose of Oral Iron During the Primary Efficacy Evaluation Period in ND Participants [Weeks 40 to 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron dose during the primary efficacy evaluation period (Weeks 40 to 52) = Total oral iron dose (mg) during the primary efficacy evaluation period / (duration in the period in days / 30.4375 days). Monthly average dose of oral iron during the primary efficacy evaluation period in ND participants is presented.

45. Monthly Average Dose of Oral Iron During the Primary Efficacy Evaluation Period in PD Participants [Weeks 40 to 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron dose during the primary efficacy evaluation period (Weeks 40 to 52) = Total oral iron dose (mg) during the primary efficacy evaluation period / (duration in the period in days / 30.4375 days). Monthly average dose of oral iron during the primary efficacy evaluation period in PD participants is presented.

46. Number of ND Participants Who Used Oral Iron During the Treatment Period [Up to week 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of ND participants who used oral iron during the treatment period were summarized.

47. Number of PD Participants Who Used Oral Iron During the Treatment Period [Up to week 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of PD participants who used oral iron during the treatment period were summarized.

48. Percentage of ND Participants Who Used Oral Iron During the Treatment Period [Up to week 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of ND participants who used oral iron during the treatment period were summarized.

49. Percentage of PD Participants Who Used Oral Iron During the Treatment Period [Up to week 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of PD participants who used oral iron during the treatment period were summarized.

50. Number of ND Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period [Weeks 40 to 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of ND participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.

51. Number of PD Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period [Weeks 40 to 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of PD participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.

52. Percentage of ND Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period [Weeks 40 to 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of ND participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.

53. Percentage of PD Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period [Weeks 40 to 52]

    Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of PD participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.

54. Change From Baseline in Ferritin in ND Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Change from Baseline in Ferritin in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Ferritin is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.

55. Change From Baseline in Ferritin in PD Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Change from Baseline in Ferritin in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Ferritin is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.

56. Percent Change From Baseline in Transferrin Saturation (TSAT) in ND Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Percent change from Baseline in TSAT in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in TSAT is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.

57. Percent Change From Baseline in TSAT in PD Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Percent change from Baseline in TSAT in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in TSAT is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.

58. Percent Change From Baseline in Hepcidin in ND Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Percent change from Baseline in Hepcidin in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in Hepcidin is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.

59. Percent Change From Baseline in Hepcidin in PD Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Percent change from Baseline in Hepcidin in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in Hepcidin is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.

60. Change From Baseline in Serum Iron in ND Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Change from Baseline in serum iron in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Serum iron is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.

61. Change From Baseline in Serum Iron in PD Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Change from Baseline in serum iron in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Serum iron is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.

62. Change From Baseline in Total Iron Binding Capacity (TIBC) in ND Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Change from Baseline in TIBC in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in TIBC is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.

63. Change From Baseline in TIBC in PD Participants [Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52]

    Change from Baseline in TIBC in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in TIBC is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.

64. Area Under the Concentration-time Curve From Time Zero Extrapolated to 4 Hours (AUC[0-4]) of Daprodustat for All Dose Levels in ND and PD Participants [1, 2, 3 and 4 hours post dose at Weeks 12 and 24]

    Blood samples were collected at indicated timepoints. Pharmacokinetic (PK) parameters of Daprodustat were calculated using non-compartmental method. AUC (0-4) is presented for combined Week 12 and 24. Geometric mean and geometric coefficient of variation is presented. NA indicates that the data is not available since geometric coefficient of variation could not be calculated for a single participant.

65. Maximum Observed Concentration (Cmax) of Daprodustat for All Dose Levels in ND and PD Participants [1, 2, 3 and 4 hours post dose at Weeks 12 and 24]

    Blood samples were collected at indicated timepoints. PK parameters of Daprodustat were calculated using non-compartmental method. Cmax is presented for combined Week 12 and 24. Geometric mean and geometric coefficient of variation is presented. NA indicates that the data is not available since geometric coefficient of variation could not be calculated for a single participant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age (at the time of informed consent): >=20 years of age

• Screening verification only: Stage of chronic kidney disease (CKD) (ND subjects only): CKD stages 3, 4, and 5 defined by estimated glomerular filtration rate (eGFR) using the Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) formula

• Dialysis:

• Not on dialysis for at least 12 weeks prior to screening (ND subjects)

• On peritoneal dialysis (PD subjects)

• Use of ESA:

• ESA non-users: Have not used ESAs for 8 weeks prior to screening

• ESA users: Have used the same ESA for 8 weeks prior to screening. However, in the ND subjects, the dose of darbepoetin alfa or epoetin beta pegol must be stable (administered once every 4 weeks and up to one-step dose change during 8 weeks prior to screening).

• Hgb: Determined at the site using an Hgb analyzer

• ESA non-users: >=8.0 g/dL and <11.0 g/dL

• ESA users: >=9.0 g/dL and <=13.0 g/dL

• Iron parameters: Ferritin >100 nanograms per milliliters (ng/mL) or transferrin saturation (TSAT) >20% (screening verification only)

• Gender (screening verification only): Female or male. Females: Not pregnant [demonstrated to be negative for human chorionic gonadotropin (hCG) in urine or serum], not breast-feeding, and meet at least one of the following:

1. Females of non-childbearing potential are defined as follows:

• Pre-menopausal with at least one of the following and no plans to utilize assisted reproductive techniques (e.g., in vitro fertilization or donor embryo transfer):

• History of bilateral tubal ligation or salpingectomy

• History of hysteroscopic tubal occlusion and postoperatively documented bilateral tubal obstruction

• History of hysterectomy

• History of bilateral oophorectomy

• Postmenopausal defined as: females 60 years of age or older or ; In females <60 years of age, 12 months of spontaneous amenorrhea (in questionable cases a blood sample with postmenopausal follicle stimulating hormone [FSH] and estradiol concentrations is confirmatory [specified reference ranges]). Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the most effective contraception methods if they wish to continue their HRT during the study. Otherwise they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

1. Females of childbearing potential must agree to comply with one of the contraception methods listed as requirements in "GSK Listing of Most Effective Contraceptive Methods for Females of Childbearing Potential" from 28 days prior to the first dose of study medication until the completion of the follow-up visit (for subjects randomized to the GSK1278863 group) or 7 weeks after the last dose of study treatment (for subjects randomized to the Epoetin beta pegol group).

• Informed consent: Written informed consent, including adherence to the requirements and conditions specified in the consent form and the protocol, must be obtained from each subject as specified in Protocol.

Exclusion Criteria:

Chronic kidney disease (CKD)-related criteria

• Dialysis

• Cohort 1 and Cohort 3: Start or plan to initiate dialysis during the study

• Cohort 2: Plan to stop peritoneal dialysis or start hemodialysis during the study

• Kidney transplant: Planned living-related kidney transplant during the study Anemia-related criteria

• Aplasia: History of bone-marrow hypoplasia or pure red cell aplasia

• Other causes of anemia: pernicious anemia, thalassemia, sickle cell anemia, or myelodysplastic syndromes

• Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within 8 weeks prior to screening or during a period from screening to Day 1.

Cardiovascular disease-related criteria

• Myocardial infarction, acute coronary syndrome, stroke, or transient ischemic attack: Diagnosed within 8 weeks prior to screening or during a period from screening to Day

• Heart failure: Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system

• QT interval corrected for heart rate (QTc) (screening verification only): QTc >500 milliseconds (msec) or QTc >530 msec in subjects with bundle branch block Note: QT interval corrected using the Bazett's formula (QTcB) will be used, and Electrocardiogram (ECG) can be mechanically or manually read.

Other disease-related criteria

• Liver disease (if any of the following occurs):

• (Screening verification only) Alanine transaminase (ALT) >2 times upper limit of normal (ULN)

• (Screening verification only) Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)

• Current unstable active liver or biliary disease (generally defined by the onset of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, persistent jaundice, or cirrhosis) Note: Stable liver disease (including asymptomatic gallstones, chronic hepatitis B/C, or Gilbert's syndrome) is acceptable if the subject otherwise meets entry criteria..

• Malignancy: History of malignancy within 2 years prior to screening, or currently receiving treatment for cancer, (PD subjects only) complex renal cystic >3 centimeters (cm) (II F, III or IV based on the Bosniak classification) Note (ND subjects and PD subjects): The only exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated >=8 weeks before screening.

• In the opinion of the investigator, Hgb increase to the target range (11.0-13.0 g/dL) is medically risky.

Concomitant medication and other study treatment-related criteria

• Iron: Planned use of intravenous iron during the screening phase or during a period from Day 1 to Week 4 Note: Oral iron is acceptable. However, the same dose regimen must be used throughout the screening phase and from Day 1 to Week 4. Antihyperphosphatemic agents containing iron (e.g., ferric citrate hydrate) are also acceptable only if used for at least 12 weeks prior to screening. However, they must be continued throughout the screening phase from Day 1 to Week 4.

• Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product or epoetin beta pegol

• Drugs and supplements: Use or planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited during the study period (prohibited medications: strong inducers and inhibitor of Cytochrome P450 2C8 [CYP2C8])

• Prior investigational product exposure: Use of an investigational agent within 30 days or five half lives of the investigational agent (whichever is longer)

• Prior treatment with GSK1278863: Any prior treatment with GSK1278863 for a treatment duration of >30 days

General health-related criteria

• Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator (or subinvestigator) considers would put the subject at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Aichi		Japan	453-8566
2	GSK Investigational Site	Aichi		Japan	455-8530
3	GSK Investigational Site	Aichi		Japan	457-8511
4	GSK Investigational Site	Aichi		Japan	486-8510
5	GSK Investigational Site	Chiba		Japan	260-8712
6	GSK Investigational Site	Chiba		Japan	278-0004
7	GSK Investigational Site	Ehime		Japan	790-0024
8	GSK Investigational Site	Fukui		Japan	910-8526
9	GSK Investigational Site	Fukuoka		Japan	802-8555
10	GSK Investigational Site	Fukuoka		Japan	820-8505
11	GSK Investigational Site	Fukushima		Japan	963-8052
12	GSK Investigational Site	Gifu		Japan	500-8523
13	GSK Investigational Site	Gifu		Japan	500-8717
14	GSK Investigational Site	Hiroshima		Japan	720-0838
15	GSK Investigational Site	Hokkaido		Japan	007-0803
16	GSK Investigational Site	Hokkaido		Japan	060-0033
17	GSK Investigational Site	Hokkaido		Japan	065-8611
18	GSK Investigational Site	Hokkaido		Japan	073-0022
19	GSK Investigational Site	Hokkaido		Japan	073-0196
20	GSK Investigational Site	Ibaraki		Japan	302-0022
21	GSK Investigational Site	Ibaraki		Japan	306-0433
22	GSK Investigational Site	Ibaraki		Japan	310-0015
23	GSK Investigational Site	Ishikawa		Japan	920-0353
24	GSK Investigational Site	Ishikawa		Japan	920-8530
25	GSK Investigational Site	Iwate		Japan	020-0066
26	GSK Investigational Site	Kagoshima		Japan	890-0073
27	GSK Investigational Site	Kagoshima		Japan	893-0024
28	GSK Investigational Site	Kagoshima		Japan	899-5431
29	GSK Investigational Site	Kanagawa		Japan	210-0852
30	GSK Investigational Site	Kanagawa		Japan	234-8503
31	GSK Investigational Site	Kanagawa		Japan	242-0018
32	GSK Investigational Site	Kanagawa		Japan	251-8550
33	GSK Investigational Site	Kumamoto		Japan	861-8520
34	GSK Investigational Site	Kumamoto		Japan	862-8505
35	GSK Investigational Site	Kyoto		Japan	604-8845
36	GSK Investigational Site	Kyoto		Japan	611-0041
37	GSK Investigational Site	Kyoto		Japan	612-8555
38	GSK Investigational Site	Nagano		Japan	396-8555
39	GSK Investigational Site	Nagano		Japan	399-8292
40	GSK Investigational Site	Oita		Japan	874-0011
41	GSK Investigational Site	Osaka		Japan	530-0012
42	GSK Investigational Site	Osaka		Japan	530-8480
43	GSK Investigational Site	Osaka		Japan	555-0001
44	GSK Investigational Site	Osaka		Japan	558-8558
45	GSK Investigational Site	Osaka		Japan	586-8521
46	GSK Investigational Site	Osaka		Japan	591-8025
47	GSK Investigational Site	Saitama		Japan	330-8553
48	GSK Investigational Site	Saitama		Japan	335-0023
49	GSK Investigational Site	Shiga		Japan	523-0082
50	GSK Investigational Site	Shizuoka		Japan	425-8505
51	GSK Investigational Site	Tokushima		Japan	770-0011
52	GSK Investigational Site	Tokyo		Japan	141-8625
53	GSK Investigational Site	Tottori		Japan	683-0002
54	GSK Investigational Site	Toyama		Japan	932-8503
55	GSK Investigational Site	Toyama		Japan	937-0042
56	GSK Investigational Site	Toyama		Japan	938-8502

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jul 3, 2017
• Statistical Analysis Plan - Nov 19, 2018

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02791763
• Other Study ID Numbers: 201753
• First Posted: Jun 7, 2016
• Last Update Posted: May 18, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Renal Anemia; Japanese; chronic kidney disease; Peritoneal dialysis; GSK1278863; Non-dialysis
• Additional relevant MeSH terms: Anemia; Glycine

Study Results

Participant Flow

Recruitment Details	This was an open-label, active-controlled, parallel-group, multi-center study to compare the efficacy (verification of non-inferiority) and safety of GSK1278863 (daprodustat) versus epoetin beta pegol in Japanese non-dialysis (ND) participants, including an open-label non-comparative cohort of peritoneal dialysis (PD) participants.
Pre-assignment Detail	A total of 56 centers, contracted in Japan, enrolled and randomized participants. A total of 455 participants were screened and 355 participants were enrolled and randomized in this study.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants	Daprodustat in PD Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Period Title: Overall Study
STARTED	149	150	56
COMPLETED	111	113	43
NOT COMPLETED	38	37	13

Baseline Characteristics

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants	Daprodustat in PD Participants	Total
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.	Total of all reporting groups
Overall Participants	149	150	56	355
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.2 (11.57)	70.3 (9.09)	64.4 (9.64)	68.5 (10.45)
Sex: Female, Male (Count of Participants)
Female	53 35.6%	58 38.7%	12 21.4%	123 34.6%
Male	96 64.4%	92 61.3%	44 78.6%	232 65.4%
Race/Ethnicity, Customized (Count of Participants) [Number]
Asian- Japanese Heritage	149 100%	150 100%	56 100%	355 100%

Outcome Measures

1. Primary Outcome

Title	Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants
Description	The mean hemoglobin during the primary efficacy evaluation period in ND participants was estimated by a statistical model using Mixed Model Repeated Measures (MMRM).
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) Population comprised of cohort 1 participants (only erythropoiesis stimulating agent [ESA] users) and cohort 3 participants (both ESA users and ESA non-users) who were given randomization number with Hgb measurement at both Baseline and at least one scheduled visits following the Baseline.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Mean (Standard Error) [Grams per deciliter (g/dL)]	11.97 (0.061)	11.86 (0.063)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daprodustat in ND Participants, Epoetin Beta Pegol in ND Participants
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was to be established as the lower limit of the 95% confidence interval (CI) for the treatment difference was greater than the pre-specified non-inferiority margin (-1.0 g/dL).
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	The p value on this table is one-sided and calculated for the non-inferiority assessment.
	Method	Mixed model repeated measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.088
	Estimation Comments	Analysis was performed by a MMRM with covariates of treatment, Baseline Hgb, visit, treatment-by-visit interaction and Baseline-by-visit interaction.

2. Secondary Outcome

Title	Number of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
Description	ND participants with observed mean Hgb within the target range during the primary efficacy evaluation period were summarized. Responders were defined as the participants with the mean Hgb within target range during the primary efficacy evaluation period.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Modified intent to treat (mITT) comprised of all ITT participants who had at least one Hgb measurement during the efficacy evaluation period.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	88	87
Responder	81 54.4%	80 53.3%
Non-Responder	7 4.7%	7 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daprodustat in ND Participants, Epoetin Beta Pegol in ND Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4941
	Comments	The p value on this table is one-sided and calculated for the superiority assessment.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.33 to 3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by logistic regression with covariates of treatment, Baseline Hgb, and Baseline ESA use.

3. Secondary Outcome

Title	Percentage of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)
Description	The percentage of ND participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Responders were defined as the participants with the mean Hgb within target range during the primary efficacy evaluation period.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	88	87
Responder	92 61.7%	92 61.3%
Non-Responder	8 5.4%	8 5.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daprodustat in ND Participants, Epoetin Beta Pegol in ND Participants
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4941
	Comments	The p value on this table is one-sided and calculated for the superiority assessment.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.33 to 3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by logistic regression with covariates of treatment, Baseline Hgb, and Baseline ESA use.

4. Secondary Outcome

Title	Change From Baseline in Hgb at Week 4 in ND Participants
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb at Week 4 in ND participants is presented.
Time Frame	Baseline (Day 1) and Week 4

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
Mean (Standard Deviation) [g/dL]	0.47 (0.878)	0.26 (0.711)

5. Secondary Outcome

Title	Change From Baseline in Hgb at Week 4 in PD Participants
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb at week 4 in PD participants is presented.
Time Frame	Baseline (Day 1) and Week 4

Outcome Measure Data

Analysis Population Description

Efficacy peritoneal dialysis (PD) Population comprised of PD participants who were given randomization number with Hgb measurement at both Baseline and at least one scheduled visits following the Baseline.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Mean (Standard Deviation) [g/dL]	-0.09 (0.899)

6. Secondary Outcome

Title	Number of ND Participants by Hgb Change From Baseline Category at Week 4
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.
Time Frame	Baseline (Day 1) and Week 4

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
<=-2.0	1 0.7%	2 1.3%
>-2.0 and <=-1.0	4 2.7%	3 2%
>-1.0 and <=0	28 18.8%	33 22%
>0 and <=1.0	43 28.9%	56 37.3%
>1.0 and <=2.0	29 19.5%	15 10%
>2.0	2 1.3%	0 0%
within +/- 1.0	72 48.3%	90 60%
over +/- 2.0	3 2%	1 0.7%

7. Secondary Outcome

Title	Percentage of ND Participants by Hgb Change From Baseline Category at Week 4
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.
Time Frame	Baseline (Day 1) and Week 4

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
<=-2.0	1 0.7%	2 1.3%
>-2.0 and <=-1.0	4 2.7%	3 2%
>-1.0 and <=0	26 17.4%	30 20%
>0 and <=1.0	40 26.8%	51 34%
>1.0 and <=2.0	27 18.1%	14 9.3%
>2.0	2 1.3%	0 0%
within +/- 1.0	67 45%	83 55.3%
over +/- 2.0	3 2%	1 0.7%

8. Secondary Outcome

Title	Number of PD Participants by Hgb Change From Baseline Category at Week 4
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.
Time Frame	Baseline (Day 1) and Week 4

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
<=-2.0	0 0%
>-2.0 and <=-1.0	10 6.7%
>-1.0 and <=0	20 13.4%
>0 and <=1.0	20 13.4%
>1.0 and <=2.0	4 2.7%
>2.0	1 0.7%
within +/- 1.0	41 27.5%
over +/- 2.0	1 0.7%

9. Secondary Outcome

Title	Percentage of PD Participants by Hgb Change From Baseline Category at Week 4
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4.
Time Frame	Baseline (Day 1) and Week 4

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
<=-2.0	0 0%
>-2.0 and <=-1.0	18 12.1%
>-1.0 and <=0	36 24.2%
>0 and <=1.0	36 24.2%
>1.0 and <=2.0	7 4.7%
>2.0	2 1.3%
within +/- 1.0	75 50.3%
over +/- 2.0	2 1.3%

10. Secondary Outcome

Title	Daprodustat Dose Level by Visit in ND Participants
Description	Daprodustat dose level at each assessment visit for ND participants is presented using 25th percentile (P25), median, and 75th percentile (P75).
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.
Measure Participants	108
Day 1, n=108	4.0
Week 4, n=106	4.0
Week 8, n=106	4.0
Week 12, n=106	4.0
Week 16, n=103	4.0
Week 20, n=100	4.0
Week 24, n=96	4.0
Week 28, n=94	4.0
Week 32, n=92	4.0
Week 36, n=89	4.0
Week 40, n=88	4.0
Week 44, n=88	4.0
Week 48, n=87	4.0

11. Secondary Outcome

Title	Epoetin Beta Pegol Dose Level by Visit in ND Participants
Description	Dose of epoetin beta pegol at a scheduled visit was converted to dose per 4 weeks when the dose frequency was every 2 weeks. Epoetin beta pegol dose level at each assessment visit for ND participants is presented using 25th percentile (P25), median, and 75th percentile (P75).
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	109
Day 1, n=109	50.0
Week 4, n=109	75.0
Week 8, n=107	100.0
Week 12, n=105	100.0
Week 16, n=104	75.0
Week 20, n=100	75.0
Week 24, n=97	75.0
Week 28, n=92	75.0
Week 32, n=90	75.0
Week 36, n=88	75.0
Week 40, n=87	75.0
Week 44, n=84	100.0
Week 48, n=82	100.0

12. Secondary Outcome

Title	Daprodustat Dose Level by Visit in PD Participants
Description	Daprodustat dose level at each assessment visit for PD participants is presented using 25th percentile (P25), median, and 75th percentile (P75).
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Day 1, n=55	4.0
Week 4, n=55	6.0
Week 8, n=52	6.0
Week 12, n=52	6.0
Week 16, n=51	6.0
Week 20, n=50	6.0
Week 24, n=48	8.0
Week 28, n=45	8.0
Week 32, n=45	6.0
Week 36, n=45	8.0
Week 40, n=44	6.0
Week 44, n=43	6.0
Week 48, n=43	6.0

13. Secondary Outcome

Title	Duration of Treatment Interruption Due to Hgb >13 g/dL in ND Participants
Description	The duration (in days) of treatment interruption due to Hgb >13 g/dL per participant was summarized descriptively on participants with a period of treatment interruption due to Hgb >13 g/dL.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who had Hgb > 13.0 g/dL of Hemocue were included in analysis.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	42	39
Median (Full Range) [Days]	28.0	28.0

14. Secondary Outcome

Title	Duration of Treatment Interruption Due to Hgb >13 g/dL in PD Participants
Description	The duration (in days) of treatment interruption due to Hgb >13 g/dL per participant was summarized descriptively on participants with a period of treatment interruption due to Hgb >13 g/dL.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants who had Hgb > 13.0 g/dL of Hemocue were included in analysis.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	23
Median (Full Range) [Days]	28.0

15. Secondary Outcome

Title	Number of Dose Adjustments in ND Participants
Description	Number of dose adjustments in ND participants is presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Median (Full Range) [Number of dose adjustments]	5.0	6.0

16. Secondary Outcome

Title	Number of Dose Adjustments in PD Participants
Description	Number of dose adjustments in PD participants is presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Median (Full Range) [Number of dose adjustments]	5.0

17. Secondary Outcome

Title	Hgb Values at Each Assessment Visit in ND Participants
Description	Hgb values at each assessment visit for ND participants is presented.
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Day 1, n=108,109	10.48 (1.140)	10.68 (1.066)
Week 4, n=107,109	10.95 (1.122)	10.94 (1.024)
Week 8, n=107,109	11.19 (1.092)	11.34 (0.905)
Week 12, n=106,107	11.51 (1.024)	11.84 (0.880)
Week 16, n=104,105	11.90 (1.091)	12.07 (1.073)
Week 20, n=102,103	11.84 (0.909)	11.96 (0.820)
Week 24, n=99,99	11.87 (0.740)	11.80 (0.855)
Week 28, n=96,93	11.98 (0.845)	11.83 (0.859)
Week 32, n=92,90	12.03 (0.785)	11.80 (0.875)
Week 36, n=92,88	11.93 (0.730)	11.81 (0.810)
Week 40, n=88,87	11.88 (0.735)	12.00 (0.857)
Week 44, n=88,86	11.87 (0.868)	11.75 (0.763)
Week 48, n=87,83	12.05 (0.896)	11.80 (0.904)
Week 52, n=87,81	12.01 (1.003)	11.99 (0.930)

18. Secondary Outcome

Title	Hgb Values at Each Assessment Visit in PD Participants
Description	Hgb values at each assessment visit for PD participants is presented.
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Day 1, n=55	10.85 (0.964)
Week 4, n=55	10.77 (1.239)
Week 8, n=54	10.83 (1.259)
Week 12, n=52	11.36 (1.097)
Week 16, n=51	11.42 (1.079)
Week 20, n=50	11.54 (0.807)
Week 24, n=49	11.69 (0.816)
Week 28, n=48	11.95 (1.038)
Week 32, n=45	12.07 (0.890)
Week 36, n=45	11.90 (0.839)
Week 40, n=44	12.12 (0.795)
Week 44, n=43	11.92 (0.824)
Week 48, n=43	12.10 (0.774)
Week 52, n=43	12.12 (0.699)

19. Secondary Outcome

Title	Change From Baseline in Hgb Values at Each Assessment Visit in ND Participants
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb values at each assessment visit in ND participants is presented.
Time Frame	Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
Week 4, n=107,109	0.47 (0.878)	0.26 (0.711)
Week 8, n=107,109	0.71 (1.122)	0.66 (1.109)
Week 12, n=106,107	1.04 (1.352)	1.18 (1.384)
Week 16, n=104,105	1.45 (1.376)	1.40 (1.495)
Week 20, n=102,103	1.39 (1.330)	1.26 (1.336)
Week 24, n=99,99	1.41 (1.346)	1.10 (1.295)
Week 28, n=96,93	1.54 (1.375)	1.08 (1.151)
Week 32, n=92,90	1.60 (1.371)	1.04 (1.299)
Week 36, n=92,88	1.49 (1.265)	1.04 (1.294)
Week 40, n=88,87	1.44 (1.371)	1.26 (1.304)
Week 44, n=88,86	1.43 (1.435)	1.01 (1.131)
Week 48, n=87,83	1.61 (1.350)	1.03 (1.172)
Week 52, n=87,81	1.56 (1.527)	1.21 (1.432)

20. Secondary Outcome

Title	Change From Baseline in Hgb Values at Each Assessment Visit in PD Participants
Description	Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb values at each assessment visit in PD participants is presented.
Time Frame	Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Week 4, n=55	-0.09 (0.899)
Week 8, n=54	-0.06 (1.127)
Week 12, n=52	0.44 (1.173)
Week 16, n=51	0.52 (1.295)
Week 20, n=50	0.63 (1.158)
Week 24, n=49	0.74 (1.182)
Week 28, n=48	1.00 (1.317)
Week 32, n=45	1.13 (1.192)
Week 36, n=45	0.95 (1.106)
Week 40, n=44	1.13 (1.227)
Week 44, n=43	0.90 (1.093)
Week 48, n=43	1.08 (1.248)
Week 52, n=43	1.10 (1.226)

21. Secondary Outcome

Title	Number of ND Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit
Description	Number of ND participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Day 1, n=108,109	29 19.5%	36 24%
Week 4, n=107,109	43 28.9%	48 32%
Week 8, n=107,109	64 43%	73 48.7%
Week 12, n=106,107	78 52.3%	85 56.7%
Week 16, n=104,105	84 56.4%	80 53.3%
Week 20, n=102,103	88 59.1%	85 56.7%
Week 24, n=99,99	86 57.7%	85 56.7%
Week 28, n=96,93	77 51.7%	73 48.7%
Week 32, n=92,90	79 53%	67 44.7%
Week 36, n=92,88	79 53%	70 46.7%
Week 40, n=88,87	78 52.3%	72 48%
Week 44, n=88,86	71 47.7%	68 45.3%
Week 48, n=87,83	75 50.3%	62 41.3%
Week 52, n=87,81	67 45%	59 39.3%

22. Secondary Outcome

Title	Percentage of ND Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit
Description	Percentage of ND participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Day 1, n=108,109	27 18.1%	33 22%
Week 4, n=107,109	40 26.8%	44 29.3%
Week 8, n=107,109	60 40.3%	67 44.7%
Week 12, n=106,107	74 49.7%	79 52.7%
Week 16, n=104,105	81 54.4%	76 50.7%
Week 20, n=102,103	86 57.7%	83 55.3%
Week 24, n=99,99	87 58.4%	86 57.3%
Week 28, n=96,93	80 53.7%	78 52%
Week 32, n=92,90	86 57.7%	74 49.3%
Week 36, n=92,88	86 57.7%	80 53.3%
Week 40, n=88,87	89 59.7%	83 55.3%
Week 44, n=88,86	81 54.4%	79 52.7%
Week 48, n=87,83	86 57.7%	75 50%
Week 52, n=87,81	77 51.7%	73 48.7%

23. Secondary Outcome

Title	Number of PD Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit
Description	Number of PD participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Day 1, n=55	28 18.8%
Week 4, n=55	25 16.8%
Week 8, n=54	26 17.4%
Week 12, n=52	32 21.5%
Week 16, n=51	32 21.5%
Week 20, n=50	38 25.5%
Week 24, n=49	36 24.2%
Week 28, n=48	39 26.2%
Week 32, n=45	34 22.8%
Week 36, n=45	36 24.2%
Week 40, n=44	34 22.8%
Week 44, n=43	33 22.1%
Week 48, n=43	36 24.2%
Week 52, n=43	38 25.5%

24. Secondary Outcome

Title	Percentage of PD Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit
Description	Percentage of PD participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit.
Time Frame	Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Day 1, n=55	51 34.2%
Week 4, n=55	45 30.2%
Week 8, n=54	48 32.2%
Week 12, n=52	62 41.6%
Week 16, n=51	63 42.3%
Week 20, n=50	76 51%
Week 24, n=49	73 49%
Week 28, n=48	81 54.4%
Week 32, n=45	76 51%
Week 36, n=45	80 53.7%
Week 40, n=44	77 51.7%
Week 44, n=43	77 51.7%
Week 48, n=43	84 56.4%
Week 52, n=43	88 59.1%

25. Secondary Outcome

Title	Percentage of Time With Hgb Within the Target Range (11.0 to 13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants
Description	Mean percentage of time with Hgb within the target range (11.0 to 13.0 g/dL) is summarized during the primary efficacy evaluation period (Weeks 40 to 52).
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	88	87
Mean (Standard Deviation) [Percentage of time]	85.44 (22.473)	80.57 (25.973)

26. Secondary Outcome

Title	Percentage of Time With Hgb Within the Target Range (11.0 to 13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in PD Participants
Description	Mean percentage of time with Hgb within the target range (11.0 to 13.0 g/dL) is summarized during the primary efficacy evaluation period (Weeks 40 to 52).
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	44
Mean (Standard Deviation) [Percentage of time]	85.73 (19.974)

27. Secondary Outcome

Title	Time to Reach the Lower Target Hgb Level (11.0 g/dL) in ND Participants
Description	The time (in days) to reach the lower target Hgb level (11.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. Participants who did not reach the lower Hgb target were considered as censored cases. Participants who were randomized as Hgb >= 11.0 g/dL were excluded in this summary.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who experienced this event were included in analysis.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	76	75
Median (Inter-Quartile Range) [Days]	58.0	57.0

28. Secondary Outcome

Title	Time to Reach the Lower Target Hgb Level (11.0 g/dL) in PD Participants
Description	The time (in days) to reach the lower target Hgb level (11.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. Participants who did not reach the lower Hgb target were considered as censored cases. Participants who were randomized as Hgb >= 11.0 g/dL were excluded in this summary.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants who experienced this event were included in analysis.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	27
Median (Inter-Quartile Range) [Days]	84.0

29. Secondary Outcome

Title	Number of ND Participants Who Had an Hgb Level of Less Than 7.5 g/dL
Description	Number of ND participants who had an Hgb level of less than 7.5 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Count of Participants [Participants]	1 0.7%	0 0%

30. Secondary Outcome

Title	Percentage of ND Participants Who Had an Hgb Level of Less Than 7.5 g/dL
Description	Percentage of ND participants who had an Hgb level of less than 7.5 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Number [Percentage of participants]	1 0.7%	0 0%

31. Secondary Outcome

Title	Number of PD Participants Who Had an Hgb Level of Less Than 7.5 g/dL
Description	Number of PD participants who had an Hgb level of less than 7.5 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Count of Participants [Participants]	0 0%

32. Secondary Outcome

Title	Percentage of PD Participants Who Had an Hgb Level of Less Than 7.5 g/dL
Description	Percentage of PD participants who had an Hgb level of less than 7.5 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Number [Percentage of participants]	0 0%

33. Secondary Outcome

Title	Number of ND Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Description	Number of ND participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Count of Participants [Participants]	17 11.4%	11 7.3%

34. Secondary Outcome

Title	Percentage of ND Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Description	Percentage of ND participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Number [Percentage of participants]	16 10.7%	10 6.7%

35. Secondary Outcome

Title	Number of PD Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Description	Number of PD participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Count of Participants [Participants]	11 7.4%

36. Secondary Outcome

Title	Percentage of PD Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Description	Percentage of PD participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Number [Percentage of participants]	20 13.4%

37. Secondary Outcome

Title	Number of ND Participants Who Had an Hgb Level of More Than 13.0 g/dL
Description	Number of ND participants who had an Hgb level of more than 13.0 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Count of Participants [Participants]	49 32.9%	52 34.7%

38. Secondary Outcome

Title	Percentage of ND Participants Who Had an Hgb Level of More Than 13.0 g/dL
Description	Percentage of ND participants who had an Hgb level of more than 13.0 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Number [Percentage of participants]	45 30.2%	48 32%

39. Secondary Outcome

Title	Number of PD Participants Who Had an Hgb Level of More Than 13.0 g/dL
Description	Number of PD participants who had an Hgb level of more than 13.0 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Count of Participants [Participants]	28 18.8%

40. Secondary Outcome

Title	Percentage of PD Participants Who Had an Hgb Level of More Than 13.0 g/dL
Description	Percentage of PD participants who had an Hgb level of more than 13.0 g/dL is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Number [Percentage of participants]	51 34.2%

41. Secondary Outcome

Title	Number of Episodes With Hgb Level of More Than 13.0 g/dL in ND Participants
Description	Number of episodes with Hgb level of more than 13.0 g/dL in ND participants is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Number [Episodes]	76	88

42. Secondary Outcome

Title	Number of Episodes With Hgb Level of More Than 13.0 g/dL in PD Participants
Description	Number of episodes with Hgb level of more than 13.0 g/dL in PD participants is presented.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Number [Episodes]	43

43. Secondary Outcome

Title	Monthly Average Dose of Oral Iron During the Treatment Period in ND Participants
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron = Total oral iron dose (mg) / (duration in days / 30.4375 days). Monthly average dose of oral iron during the treatment period in ND participants is presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Mean (Standard Deviation) [Milligrams]	837.37 (1209.100)	747.04 (1130.767)

44. Secondary Outcome

Title	Monthly Average Dose of Oral Iron During the Treatment Period in PD Participants
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron = Total oral iron dose (mg) / (duration in days / 30.4375 days). Monthly average dose of oral iron during the treatment period in PD participants is presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Mean (Standard Deviation) [Milligrams]	2468.68 (5418.767)

45. Secondary Outcome

Title	Monthly Average Dose of Oral Iron During the Primary Efficacy Evaluation Period in ND Participants
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron dose during the primary efficacy evaluation period (Weeks 40 to 52) = Total oral iron dose (mg) during the primary efficacy evaluation period / (duration in the period in days / 30.4375 days). Monthly average dose of oral iron during the primary efficacy evaluation period in ND participants is presented.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	88	87
Mean (Standard Deviation) [Milligrams]	967.41 (1854.896)	777.69 (1639.331)

46. Secondary Outcome

Title	Monthly Average Dose of Oral Iron During the Primary Efficacy Evaluation Period in PD Participants
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron dose during the primary efficacy evaluation period (Weeks 40 to 52) = Total oral iron dose (mg) during the primary efficacy evaluation period / (duration in the period in days / 30.4375 days). Monthly average dose of oral iron during the primary efficacy evaluation period in PD participants is presented.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	44
Mean (Standard Deviation) [Milligrams]	3038.67 (6239.034)

47. Secondary Outcome

Title	Number of ND Participants Who Used Oral Iron During the Treatment Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of ND participants who used oral iron during the treatment period were summarized.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Count of Participants [Participants]	56 37.6%	49 32.7%

48. Secondary Outcome

Title	Number of PD Participants Who Used Oral Iron During the Treatment Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of PD participants who used oral iron during the treatment period were summarized.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Count of Participants [Participants]	33 22.1%

49. Secondary Outcome

Title	Percentage of ND Participants Who Used Oral Iron During the Treatment Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of ND participants who used oral iron during the treatment period were summarized.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	108	109
Number [Percentage of participants]	52 34.9%	45 30%

50. Secondary Outcome

Title	Percentage of PD Participants Who Used Oral Iron During the Treatment Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of PD participants who used oral iron during the treatment period were summarized.
Time Frame	Up to week 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Number [Percentage of participants]	60 40.3%

51. Secondary Outcome

Title	Number of ND Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of ND participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	88	87
Count of Participants [Participants]	34 22.8%	28 18.7%

52. Secondary Outcome

Title	Number of PD Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of PD participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	44
Count of Participants [Participants]	22 14.8%

53. Secondary Outcome

Title	Percentage of ND Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of ND participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	88	87
Number [Percentage of participants]	39 26.2%	32 21.3%

54. Secondary Outcome

Title	Percentage of PD Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period
Description	Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of PD participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized.
Time Frame	Weeks 40 to 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	44
Number [Percentage of participants]	50 33.6%

55. Secondary Outcome

Title	Change From Baseline in Ferritin in ND Participants
Description	Change from Baseline in Ferritin in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Ferritin is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
Week 4, n=107,109	-41.4	-29.0
Week 16, n=104,105	-83.4	-29.3
Week 28, n=96,93	-80.1	-16.6
Week 40, n=88,87	-56.3	-16.0
Week 52, n=87,81	-42.7	-14.0

56. Secondary Outcome

Title	Change From Baseline in Ferritin in PD Participants
Description	Change from Baseline in Ferritin in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Ferritin is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Week 4, n=55	-36.4
Week 16, n=51	-81.8
Week 28, n=48	-89.1
Week 40, n=44	-74.6
Week 52, n=43	-63.6

57. Secondary Outcome

Title	Percent Change From Baseline in Transferrin Saturation (TSAT) in ND Participants
Description	Percent change from Baseline in TSAT in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in TSAT is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
Week 4, n=107,109	-12.4	-5.4
Week 16, n=104,105	-16.3	-0.3
Week 28, n=96,93	-17.5	10.6
Week 40, n=88,87	-11.2	12.5
Week 52, n=87,81	-11.7	7.0

58. Secondary Outcome

Title	Percent Change From Baseline in TSAT in PD Participants
Description	Percent change from Baseline in TSAT in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in TSAT is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Week 4, n=55	-19.2
Week 16, n=51	-29.1
Week 28, n=48	-22.6
Week 40, n=44	-19.5
Week 52, n=43	-14.7

59. Secondary Outcome

Title	Percent Change From Baseline in Hepcidin in ND Participants
Description	Percent change from Baseline in Hepcidin in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in Hepcidin is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	99	100
Week 4, n=99,100	-49.13	-19.20
Week 16, n=86,99	-55.67	-3.73
Week 28, n=81,85	-56.67	7.61
Week 40, n=76,80	-47.77	9.54
Week 52, n=76,74	-45.27	10.13

60. Secondary Outcome

Title	Percent Change From Baseline in Hepcidin in PD Participants
Description	Percent change from Baseline in Hepcidin in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in Hepcidin is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	53
Week 4, n=53	-49.79
Week 16, n=48	-62.59
Week 28, n=39	-65.37
Week 40, n=39	-67.91
Week 52, n=40	-54.77

61. Secondary Outcome

Title	Change From Baseline in Serum Iron in ND Participants
Description	Change from Baseline in serum iron in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Serum iron is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
Week 4, n=107,109	0.5	-0.8
Week 16, n=104,105	0.3	0.6
Week 28, n=96,93	0.3	2.0
Week 40, n=88,87	0.9	1.8
Week 52, n=87,81	0.7	1.1

62. Secondary Outcome

Title	Change From Baseline in Serum Iron in PD Participants
Description	Change from Baseline in serum iron in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Serum iron is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Week 4, n=55	-1.2
Week 16, n=51	-2.4
Week 28, n=48	-1.0
Week 40, n=44	-0.4
Week 52, n=43	1.0

63. Secondary Outcome

Title	Change From Baseline in Total Iron Binding Capacity (TIBC) in ND Participants
Description	Change from Baseline in TIBC in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in TIBC is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in ND Participants	Epoetin Beta Pegol in ND Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.	Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.
Measure Participants	107	109
Week 4, n=107,109	6.9	0.5
Week 16, n=104,105	9.9	1.9
Week 28, n=96,93	9.9	1.4
Week 40, n=88,87	8.0	0.2
Week 52, n=87,81	7.8	0.1

64. Secondary Outcome

Title	Change From Baseline in TIBC in PD Participants
Description	Change from Baseline in TIBC in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in TIBC is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction.
Time Frame	Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Outcome Measure Data

Analysis Population Description

Efficacy PD Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Daprodustat in PD Participants
Arm/Group Description	Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
Measure Participants	55
Week 4, n=55	6.9
Week 16, n=51	9.5
Week 28, n=48	11.0
Week 40, n=44	11.0
Week 52, n=43	9.6

65. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time Zero Extrapolated to 4 Hours (AUC[0-4]) of Daprodustat for All Dose Levels in ND and PD Participants
Description	Blood samples were collected at indicated timepoints. Pharmacokinetic (PK) parameters of Daprodustat were calculated using non-compartmental method. AUC (0-4) is presented for combined Week 12 and 24. Geometric mean and geometric coefficient of variation is presented. NA indicates that the data is not available since geometric coefficient of variation could not be calculated for a single participant.
Time Frame	1, 2, 3 and 4 hours post dose at Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

PK Population comprised of all Daprodustat-treated participants from whom PK samples were collected and analyzed. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat 1 mg	Daprodustat 2 mg	Daprodustat 4 mg	Daprodustat 6 mg	Daprodustat 8 mg	Daprodustat 12 mg	Daprodustat 18 mg	Daprodustat 24 mg
Arm/Group Description	Participants received oral daprodustat tablet (1 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral daprodustat tablet (2 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral daprodustat tablet (4 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral daprodustat tablet (6 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 8 mg daprodustat (4 mg*2 tablets) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 12 mg of daprodustat (6 mg*2 tablets) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 18 mg of daprodustat (6 mg*3 tablets) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 24 mg of daprodustat (6 mg*4 tablets) once on the day of PK sampling at Week 12 or 24.
Measure Participants	13	68	113	83	66	16	7	1
Geometric Mean (Geometric Coefficient of Variation) [Hour*nanogram per milliliter]	35.3199 (38.4)	63.0175 (89.8)	101.9293 (96.5)	152.4966 (83.2)	167.6515 (105.9)	190.0962 (65.9)	435.6847 (131.7)	404.0567 (NA)

66. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Daprodustat for All Dose Levels in ND and PD Participants
Description	Blood samples were collected at indicated timepoints. PK parameters of Daprodustat were calculated using non-compartmental method. Cmax is presented for combined Week 12 and 24. Geometric mean and geometric coefficient of variation is presented. NA indicates that the data is not available since geometric coefficient of variation could not be calculated for a single participant.
Time Frame	1, 2, 3 and 4 hours post dose at Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Daprodustat 1 mg	Daprodustat 2 mg	Daprodustat 4 mg	Daprodustat 6 mg	Daprodustat 8 mg	Daprodustat 12 mg	Daprodustat 18 mg	Daprodustat 24 mg
Arm/Group Description	Participants received oral daprodustat tablet (1 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral daprodustat tablet (2 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral daprodustat tablet (4 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral daprodustat tablet (6 mg) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 8 mg daprodustat (4 mg*2 tablets) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 12 mg of daprodustat (6 mg*2 tablets) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 18 mg of daprodustat (6 mg*3 tablets) once on the day of PK sampling at Week 12 or 24.	Participants received oral dose of 24 mg of daprodustat (6 mg*4 tablets) once on the day of PK sampling at Week 12 or 24.
Measure Participants	13	68	113	83	66	16	7	1
Geometric Mean (Geometric Coefficient of Variation) [Nanogram per milliliter]	17.6522 (36.5)	35.0709 (91.2)	58.6098 (83.2)	81.1851 (82.6)	91.0731 (95.4)	94.1242 (73.3)	197.9290 (159.6)	226.0000 (NA)

Adverse Events

Time Frame	On-therapy serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment up to Week 52 for both ND and PD participants.
Adverse Event Reporting Description	SAEs and non-serious AEs were reported treatment-wise for the Safety Population which comprised of all randomized participants who received at least 1 dose of study treatment.
Arm/Group Title	Daprodustat in ND Participants		Epoetin Beta Pegol in ND Participants		Daprodustat in PD Participants
Arm/Group Description	Eligible ND participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams [mg] as recommended) dose once daily for 52 weeks.		Eligible ND participants received subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram [µg] as recommended) dose once every 2 or 4 weeks for 52 weeks.		Eligible PD participants received oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.
All Cause Mortality
	Daprodustat in ND Participants		Epoetin Beta Pegol in ND Participants		Daprodustat in PD Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/149 (0.7%)		2/150 (1.3%)		0/56 (0%)
Serious Adverse Events
	Daprodustat in ND Participants		Epoetin Beta Pegol in ND Participants		Daprodustat in PD Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/149 (22.8%)		43/150 (28.7%)		26/56 (46.4%)
Cardiac disorders
Cardiac failure congestive	0/149 (0%)	0	5/150 (3.3%)	7	3/56 (5.4%)	3
Arrhythmia	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Cardiac failure	0/149 (0%)	0	1/150 (0.7%)	1	1/56 (1.8%)	1
Prinzmetal angina	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Ear and labyrinth disorders
Sudden hearing loss	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Endocrine disorders
Adrenocortical insufficiency acute	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Eye disorders
Cataract	1/149 (0.7%)	1	1/150 (0.7%)	1	0/56 (0%)	0
Gastrointestinal disorders
Large intestine polyp	1/149 (0.7%)	1	1/150 (0.7%)	1	0/56 (0%)	0
Diarrhoea	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Inguinal hernia	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Pancreatitis acute	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Vomiting	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
General disorders
Oedema	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Pyrexia	0/149 (0%)	0	1/150 (0.7%)	1	1/56 (1.8%)	1
Chest pain	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Infections and infestations
Pneumonia	1/149 (0.7%)	1	1/150 (0.7%)	1	0/56 (0%)	0
Gastroenteritis	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Pyelonephritis acute	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Peritonitis	0/149 (0%)	0	0/150 (0%)	0	9/56 (16.1%)	12
Bronchitis	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Catheter site infection	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	2
Pharyngitis	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Injury, poisoning and procedural complications
Brain contusion	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Subcutaneous haematoma	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Forearm fracture	0/149 (0%)		0/150 (0%)		1/56 (1.8%)	1
Metabolism and nutrition disorders
Dehydration	0/149 (0%)	0	2/150 (1.3%)	2	1/56 (1.8%)	1
Hyperkalaemia	1/149 (0.7%)	1	1/150 (0.7%)	1	0/56 (0%)	0
Hyponatraemia	2/149 (1.3%)	2	0/150 (0%)	0	0/56 (0%)	0
Diabetes mellitus	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Gout	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Decreased appetite	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Back pain	1/149 (0.7%)	1	0/150 (0%)	0	1/56 (1.8%)	1
Bone pain	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Osteoarthritis	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/149 (0.7%)	1	1/150 (0.7%)	1	0/56 (0%)	0
Clear cell renal cell carcinoma	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Breast cancer	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Metastases to skin	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Ovarian cancer	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Rectal cancer	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Renal cancer	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Nervous system disorders
Cerebral infarction	1/149 (0.7%)	1	1/150 (0.7%)	1	0/56 (0%)	0
Subarachnoid haemorrhage	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Spinocerebellar disorder	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Transient ischaemic attack	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Renal and urinary disorders
Renal impairment	5/149 (3.4%)	5	11/150 (7.3%)	11	0/56 (0%)	0
Chronic kidney disease	6/149 (4%)	6	8/150 (5.3%)	9	0/56 (0%)	0
End stage renal disease	3/149 (2%)	3	0/150 (0%)	0	0/56 (0%)	0
Acute kidney injury	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Renal failure	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Acute respiratory distress syndrome	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Pulmonary embolism	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Pharyngeal haematoma	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Pleural effusion	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Pulmonary congestion	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Vascular disorders
Aortic dissection	0/149 (0%)	0	1/150 (0.7%)	1	0/56 (0%)	0
Shock haemorrhagic	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Steal syndrome	1/149 (0.7%)	1	0/150 (0%)	0	0/56 (0%)	0
Peripheral arterial occlusive disease	0/149 (0%)	0	0/150 (0%)	0	1/56 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Daprodustat in ND Participants		Epoetin Beta Pegol in ND Participants		Daprodustat in PD Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/149 (57%)		91/150 (60.7%)		41/56 (73.2%)
Gastrointestinal disorders
Constipation	10/149 (6.7%)	10	18/150 (12%)	19	0/56 (0%)	0
Diarrhoea	0/149 (0%)	0	0/150 (0%)	0	7/56 (12.5%)	8
Nausea	0/149 (0%)	0	0/150 (0%)	0	6/56 (10.7%)	7
Gastrooesophageal reflux disease	0/149 (0%)	0	0/150 (0%)	0	5/56 (8.9%)	5
Vomiting	0/149 (0%)	0	0/150 (0%)	0	3/56 (5.4%)	3
General disorders
Pyrexia	0/149 (0%)	0	0/150 (0%)	0	3/56 (5.4%)	3
Infections and infestations
Nasopharyngitis	49/149 (32.9%)	68	56/150 (37.3%)	77	16/56 (28.6%)	23
Influenza	8/149 (5.4%)	8	8/150 (5.3%)	9	0/56 (0%)	0
Catheter site infection	0/149 (0%)	0	0/150 (0%)	0	9/56 (16.1%)	15
Device related infection	0/149 (0%)	0	0/150 (0%)	0	5/56 (8.9%)	6
Bronchitis	0/149 (0%)	0	0/150 (0%)	0	3/56 (5.4%)	3
Injury, poisoning and procedural complications
Contusion	5/149 (3.4%)	7	8/150 (5.3%)	9	0/56 (0%)	0
Investigations
Blood pressure increased	8/149 (5.4%)	8	4/150 (2.7%)	4	0/56 (0%)	0
Metabolism and nutrition disorders
Hyperkalaemia	11/149 (7.4%)	14	7/150 (4.7%)	7	0/56 (0%)	0
Decreased appetite	0/149 (0%)	0	0/150 (0%)	0	4/56 (7.1%)	4
Musculoskeletal and connective tissue disorders
Back pain	11/149 (7.4%)	13	11/150 (7.3%)	13	4/56 (7.1%)	4
Arthralgia	0/149 (0%)	0	0/150 (0%)	0	3/56 (5.4%)	4
Respiratory, thoracic and mediastinal disorders
Cough	0/149 (0%)	0	0/150 (0%)	0	3/56 (5.4%)	3
Skin and subcutaneous tissue disorders
Pruritus	12/149 (8.1%)	12	5/150 (3.3%)	5	0/56 (0%)	0
Vascular disorders
Hypertension	4/149 (2.7%)	4	8/150 (5.3%)	8	5/56 (8.9%)	5

Limitations/Caveats

A participant in ND daprodustat/ND epoetin beta pegol/PD daprodustat had data entry error with dose level. This had an impact on outcomes of dose level and number of dose adjustment.

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Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.