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Trial record 2 of 15 for:    GSK 1278863 | Phase 2, 3

Efficacy and Safety Study of GSK1278863 in Japanese Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Erythropoiesis Stimulating Agents

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ClinicalTrials.gov Identifier: NCT02829320
Recruitment Status : Completed
First Posted : July 12, 2016
Results First Posted : July 13, 2018
Last Update Posted : July 13, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Anaemia
Interventions Drug: GSK1278863
Drug: Iron
Enrollment 28

Recruitment Details This was a 24-week, Phase 3, open-label, non-comparative, multicenter study to evaluate the efficacy and safety of GSK1278863 in Japanese hemodialysis participants with renal anemia not using Erythropoiesis Stimulating Agents. The study was conducted at 18 centers in Japan from 08-Aug-2016 to 17-Oct-2017.
Pre-assignment Details A total of 36 participants were screened and 8 failed screening because of not meeting eligibility criteria (7) and withdrawal by participants (1). The remaining 28 participants were enrolled in this study. This study consisted of a 4-week screening period, a 24-week treatment period and a 2 to 4-week follow-up period.
Arm/Group Title All Participants
Hide Arm/Group Description Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 milligram (mg) for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain hemoglobin (Hgb) within the target range (10.0–12.0 grams per deciliter [g/dL]). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 nanogram per milliliter (ng/mL) and transferrin saturation (TSAT) is <=20%.
Period Title: Overall Study
Started 28
Completed 28
Not Completed 0
Arm/Group Title All Participants
Hide Arm/Group Description Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
All Treated Subjects
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants
62.5  (10.16)
[1]
Measure Analysis Population Description: All Treated Subjects
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female
3
  10.7%
Male
25
  89.3%
[1]
Measure Analysis Population Description: All Treated Subjects
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Count of Participants
Asian - Japanese Heritage Number Analyzed 28 participants
28
[1]
Measure Analysis Population Description: All Treated Subjects
Dialysis Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Newly started dialysis
11
  39.3%
Maintenance dialysis
17
  60.7%
[1]
Measure Description: Dialysis newly started < 12 weeks before screening was considered as Newly started dialysis. Dialysis started >= 12 weeks before screening was considered as Maintenance dialysis.
1.Primary Outcome
Title Change From Baseline in Hgb at Week 4
Hide Description Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The analysis was performed on All Treated Subjects Population which comprised of all participants who received at least one dose of GSK1278863.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: G/dL
0.79
(0.53 to 1.05)
2.Primary Outcome
Title Number of Participants by Hgb Change From Baseline Category at Week 4
Hide Description Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The change in Hgb at Week 4 was classified into different categories (i.e., <=-2.0, >-2.0 to -1.0, >-1.0 to 0, >0 to 1.0, >1.0 to 2.0, and >2 g/dL), and the number of participants in each category were summarized.
Time Frame Baseline and Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
<= -2.0
0
   0.0%
> -2.0 to -1.0
0
   0.0%
> -1.0 to 0
4
  14.3%
> 0 to 1.0
13
  46.4%
> 1.0 to 2.0
11
  39.3%
> 2.0
0
   0.0%
3.Secondary Outcome
Title Hgb Values at the Indicated Time Points
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: G/dL
Day 1 9.10  (0.696)
Week 4 9.90  (0.907)
Week 8 10.76  (0.957)
Week 12 11.09  (1.117)
Week 16 11.38  (1.286)
Week 20 11.34  (1.169)
Week 24 11.12  (1.210)
4.Secondary Outcome
Title Change From Baseline in Hgb at the Indicated Time Points
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The Baseline value was the latest pre-dose assessment. Change from Baseline at indicated time-points was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame Baseline and up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: G/dL
Week 4 0.79  (0.673)
Week 8 1.66  (0.773)
Week 12 1.98  (0.984)
Week 16 2.28  (1.248)
Week 20 2.24  (1.174)
Week 24 2.01  (1.121)
5.Secondary Outcome
Title Number of Participants Who Had Hgb Level Within the Target Range (10.0–12.0 g/dL)
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants with Hgb withinthe target range (10.0 to 12.0 g/dL) at each assessment visit was summarized.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1, within range
3
  10.7%
Week 4, within range
13
  46.4%
Week 8, within range
20
  71.4%
Week 12, within range
18
  64.3%
Week 16, within range
17
  60.7%
Week 20, within range
20
  71.4%
Week 24, within range
23
  82.1%
6.Secondary Outcome
Title Time to Reach the Lower Target Hgb Level (10.0 g/dL)
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. Participants who could not reach lower target were regarded as censored. The time (in days) to reach the lower target Hgb level (10.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Median (Inter-Quartile Range)
Unit of Measure: Days
57.0
(29.0 to 57.0)
7.Secondary Outcome
Title Number of Participants Who Had Hgb Level of Less Than 7.5 g/dL
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of less than 7.5 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
8.Secondary Outcome
Title Number of Participants Who Had Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb increase of more than 2.0 g/dL over any 4 weeks were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.6%
9.Secondary Outcome
Title Number of Participants Who Had Hgb Level of More Than 13.0 g/dL
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
3
  10.7%
10.Secondary Outcome
Title Number of Episodes of Achieving Hgb Level of More Than 13.0 g/dL
Hide Description Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of episodes in participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: Episodes
7
11.Secondary Outcome
Title Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863
Hide Description Blood samples were collected to evaluate AUC (0-4) at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Population consisted of all participants who received GSK1278863 with the PK samples collected and analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1.
Time Frame 1, 2, 3 and 4 hours post dose at Weeks 12 and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title GSK1278863 1 mg GSK1278863 2 mg GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 12 mg GSK1278863 18 mg
Hide Arm/Group Description:
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 1 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 2 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 4 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 6 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 8 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 12 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 18 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 1 12 22 13 3 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour*nanogram per milliliter (h*ng/mL)
AUC (0-4), Week 12, n=0,4,14,8,1,0,0 Number Analyzed 0 participants 4 participants 14 participants 8 participants 1 participants 0 participants 0 participants
25.7228
(289.9%)
95.1319
(111.9%)
200.6036
(62.9%)
233.3933 [1] 
(NA%)
AUC (0-4), Week 24, n=1,8,8,5,2,1,1 Number Analyzed 1 participants 8 participants 8 participants 5 participants 2 participants 1 participants 1 participants
43.3100 [1] 
(NA%)
33.8941
(230.9%)
86.3702
(58.9%)
133.3020
(50.9%)
437.0983
(18.7%)
749.4583 [1] 
(NA%)
126.2883 [1] 
(NA%)
AUC (0-4), All, n=1,12,22,13,3,1,1 Number Analyzed 1 participants 12 participants 22 participants 13 participants 3 participants 1 participants 1 participants
43.3100 [1] 
(NA%)
30.9164
(225.3%)
91.8474
(91.1%)
171.4229
(60.8%)
354.6083
(40.0%)
749.4583 [1] 
(NA%)
126.2883 [1] 
(NA%)
[1]
The dispersion was not calculated because of n=1
12.Secondary Outcome
Title Maximum Observed Concentration (Cmax) of GSK1278863
Hide Description Blood samples were collected to evaluate Cmax at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1.
Time Frame 1, 2, 3 and 4 hours post dose at Weeks 12 and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title GSK1278863 1 mg GSK1278863 2 mg GSK1278863 4 mg GSK1278863 6 mg GSK1278863 8 mg GSK1278863 12 mg GSK1278863 18 mg
Hide Arm/Group Description:
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 1 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 2 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 4 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 6 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 8 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 12 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 18 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 1 12 22 13 3 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cmax, Week 12, n=0,4,14,8,1,0,0 Number Analyzed 0 participants 4 participants 14 participants 8 participants 1 participants 0 participants 0 participants
13.9578
(340.6%)
57.6572
(81.2%)
122.9883
(56.9%)
179.0000 [1] 
(NA%)
Cmax, Week 24, n=1,8,8,5,2,1,1 Number Analyzed 1 participants 8 participants 8 participants 5 participants 2 participants 1 participants 1 participants
27.5000 [1] 
(NA%)
18.3448
(202.3%)
44.8853
(49.8%)
100.2261
(41.3%)
202.9384
(3.5%)
311.0000 [1] 
(NA%)
93.4000 [1] 
(NA%)
Cmax, All, n=1,12,22,13,3,1,1 Number Analyzed 1 participants 12 participants 22 participants 13 participants 3 participants 1 participants 1 participants
27.5000 [1] 
(NA%)
16.7474
(217.4%)
52.6391
(70.4%)
113.6784
(50.4%)
194.6229
(7.7%)
311.0000 [1] 
(NA%)
93.4000 [1] 
(NA%)
[1]
The dispersion was not calculated because of n=1
13.Secondary Outcome
Title Monthly Average Dose of Intravenous (IV) Iron During the Treatment Period
Hide Description Records of on-therapy iron medication were used to calculate average quarterly IV iron dose. Quarter 1 = (Randomization Date - Treatment Start Date at Week 12 - 1 [day]). Quarter 2 = (Treatment Start Date at Week 12 - Study Treatment Stop Date). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: Mg
Quarter 1; n= 3 Number Analyzed 3 participants
231.61  (99.916)
Quarter 2; n= 4 Number Analyzed 4 participants
217.19  (86.529)
14.Secondary Outcome
Title Number of Participants Who Used Iron During the Treatment Period
Hide Description The number of participants who used iron (both IV and oral iron) during the treatment period were summarized.
Time Frame Up to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
Oral iron
9
  32.1%
Intravenous iron
4
  14.3%
Any iron medication
12
  42.9%
15.Secondary Outcome
Title Change From Baseline in Ferritin
Hide Description Blood samples were collected from participants for measurement of serum ferritin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame Baseline and up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
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Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: Microgram per liter (µg/L)
Week 4 -80.11  (51.826)
Week 12 -126.29  (120.382)
Week 24 -107.03  (143.048)
16.Secondary Outcome
Title Percent Change From Baseline in TSAT
Hide Description Blood samples were collected from participants for measurement of TSAT at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1).
Time Frame Baseline and up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
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Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage of transferrin
Week 4
-23.06
(-32.43 to -12.38)
Week 12
-15.31
(-33.79 to 8.32)
Week 24
-10.07
(-25.49 to 8.55)
17.Secondary Outcome
Title Percent Change From Baseline in Hepcidin
Hide Description Blood samples were collected from participants for measurement of hepcidin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). If a laboratory value had a non-detectable level reported in the database, where the numeric value was missing, the value was not included in a summary. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Baseline and up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
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Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percentage of hepcidin
Week 4, n=26 Number Analyzed 26 participants
-64.78
(-71.34 to -56.71)
Week 12, n=22 Number Analyzed 22 participants
-61.74
(-74.51 to -42.57)
Week 24, n=21 Number Analyzed 21 participants
-55.67
(-72.52 to -28.47)
18.Secondary Outcome
Title Change From Baseline in Serum Iron
Hide Description Blood samples were collected from participants for measurement of serum iron at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame Baseline and up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
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Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter (µmol/L)
Week 4 -0.8123  (4.92624)
Week 12 2.0916  (10.74722)
Week 24 1.4584  (7.72121)
19.Secondary Outcome
Title Change From Baseline in Total Iron Binding Capacity (TIBC)
Hide Description Blood samples were collected from participants for measurement of TIBC at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame Baseline and up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
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Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: umol/L
Week 4 8.5904  (4.93732)
Week 12 10.8611  (6.32355)
Week 24 9.3388  (9.92131)
20.Secondary Outcome
Title Dose Level of GSK1278863 at Indicated Time Points
Hide Description Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. Mean dose during Week 12 to 24 is the average of dose at Weeks 12, 16, and 20.
Time Frame Up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Median (Full Range)
Unit of Measure: mg
Day 1
4.0
(4 to 4)
Week 4
4.0
(2 to 6)
Week 8
4.0
(2 to 8)
Week 12
4.0
(0 to 8)
Week 16
4.0
(0 to 12)
Week 20
4.0
(0 to 18)
Week 12 to 24
4.00
(0.0 to 12.7)
21.Secondary Outcome
Title Number of Participants With Frequency of Dose Adjustments
Hide Description Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. For dose adjustments frequency, the number of participants were provided by the number of dose adjustments (i.e. zero, one, two, three, four, and five or more).
Time Frame Up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
Any dose adjustments
21
  75.0%
Number of dose adjustments=0
7
  25.0%
Number of dose adjustments=1
9
  32.1%
Number of dose adjustments=2
7
  25.0%
Number of dose adjustments=3
4
  14.3%
Number of dose adjustments=4
1
   3.6%
Number of dose adjustments=5 or more
0
   0.0%
22.Secondary Outcome
Title Duration of Treatment Interruption Due to Hgb >13 g/dL
Hide Description Hgb values were used for making decision of treatment interruption. On-therapy Hgb values observed in both scheduled and unscheduled visits were counted. Participants who have no treatment interruption due to Hgb >13.0 g/dL are not included
Time Frame Up to Week 24
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All Treated Subjects Population
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
Overall Number of Participants Analyzed 3
Median (Full Range)
Unit of Measure: Days
84
(28 to 84)
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of study treatment (Day 1) until Week 24.
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs are reported for All Treated Subjects Population.
 
Arm/Group Title All Participants
Hide Arm/Group Description Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0–12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   0/28 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%) # Events
Total   3/28 (10.71%)    
Injury, poisoning and procedural complications   
Shunt occlusion  1  2/28 (7.14%)  3
Product Issues   
Device dislocation  1  1/28 (3.57%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Participants
Affected / at Risk (%) # Events
Total   12/28 (42.86%)    
Infections and infestations   
Nasopharyngitis  1  9/28 (32.14%)  10
Infected dermal cyst  1  2/28 (7.14%)  3
Injury, poisoning and procedural complications   
Shunt stenosis  1  2/28 (7.14%)  2
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02829320     History of Changes
Other Study ID Numbers: 204716
First Submitted: July 8, 2016
First Posted: July 12, 2016
Results First Submitted: May 7, 2018
Results First Posted: July 13, 2018
Last Update Posted: July 13, 2018