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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02791763
Recruitment Status : Completed
First Posted : June 7, 2016
Results First Posted : November 13, 2019
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : June 6, 2016
Actual Primary Completion Date : October 26, 2018
Actual Study Completion Date : October 26, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia

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.




Primary Outcome Measures :
  1. Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to Week 52 ]
    Number of dose adjustments in ND participants is presented.

  15. Number of Dose Adjustments in PD Participants [ Time Frame: Up to Week 52 ]
    Number of dose adjustments in PD participants is presented.

  16. Hgb Values at Each Assessment Visit in ND Participants [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
    2. 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 1.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02791763


Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] July 3, 2017
Statistical Analysis Plan  [PDF] November 19, 2018


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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02791763    
Other Study ID Numbers: 201753
First Posted: June 7, 2016    Key Record Dates
Results First Posted: November 13, 2019
Last Update Posted: November 13, 2019
Last Verified: October 2019
Keywords provided by GlaxoSmithKline:
Renal Anemia
Japanese
chronic kidney disease
Peritoneal dialysis
GSK1278863
Non-dialysis
Additional relevant MeSH terms:
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Anemia
Hematologic Diseases
Epoetin Alfa
Glycine
Hematinics
Glycine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs