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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02829320
• Collaborator: (none)
• Enrollment: 28
• Locations: 17
• Arm: 1
• Actual Duration (Months): 14.3
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This 24-week, Phase 3, open-label, non-comparative, multicentre study aims to evaluate the efficacy and safety of GSK1278863 in Japanese hemodialysis (HD) patients with renal anemia not using erythropoiesis-stimulating agents (ESAs). The primary objective is to evaluate the initial response to GSK1278863 measured by hemoglobin (Hgb) levels in HD patients not using ESAs enrolled in this study. The study is designed to evaluate the appropriateness of the starting dose of GSK1278863 and of the GSK1278863 dose adjustment regimen to achieve or maintain the target Hgb levels. This study will consist of a 4-week screening period, a 24-week treatment period (4-week fixed-dose period and a 20-week dose adjustment period), and a 2- to 4-week follow-up period.

Condition or Disease	Intervention/Treatment	Phase
Anaemia	Drug: GSK1278863; Drug: Iron	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 24-week, Phase III, Open-label, Non-comparative, Multi-center Study to Evaluate Efficacy and Safety of GSK1278863 in Japanese Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Erythropoiesis Stimulating Agents
• Actual Study Start Date: Aug 8, 2016
• Actual Primary Completion Date: May 16, 2017
• Actual Study Completion Date: Oct 17, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: GSK1278863 Subjects will receive GSK1278863 once daily orally at a starting dose of 4 milligrams (mg) on Day 1, and continued until the day of Week 4. From Weeks 4 to 24, interruption of treatment or dose adjustments will be made within the maintenance dose range of 1 mg to 24 mg according to the dose adjustment algorithm to achieve and/or maintain Hgb within the target range (10.0 to 12.0 g/dL) based on the Hgb value measured every 4 weeks. Dose changes will be made every 4 weeks. Iron replacement therapy will be given according to the standard starting criteria.

Drug: GSK1278863; GSK1278863 will be provided as round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, 4 mg or 6 mg of GSK1278863 as active ingredient.; Drug: Iron; Subjects will receive supplemental iron therapy if ferritin is <=100 ng/mL and TSAT is <=20%. The investigator (or subinvestigator) will choose the route of administration and dose of prescription iron.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hgb at Week 4 [Baseline and Week 4]

   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.

2. Number of Participants by Hgb Change From Baseline Category at Week 4 [Baseline and Week 4]

   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.

Secondary Outcome Measures

1. Hgb Values at the Indicated Time Points [Up to Week 24]

   Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer.

2. Change From Baseline in Hgb at the Indicated Time Points [Baseline and up to Week 24]

   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.

3. Number of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) [Up to Week 24]

   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.

4. Time to Reach the Lower Target Hgb Level (10.0 g/dL) [Up to Week 24]

   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.

5. Number of Participants Who Had Hgb Level of Less Than 7.5 g/dL [Up to Week 24]

   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.

6. Number of Participants Who Had Hgb Increase of More Than 2 g/dL Over Any 4 Weeks [Up to Week 24]

   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.

7. Number of Participants Who Had Hgb Level of More Than 13.0 g/dL [Up to Week 24]

   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.

8. Number of Episodes of Achieving Hgb Level of More Than 13.0 g/dL [Up to Week 24]

   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.

9. Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863 [1, 2, 3 and 4 hours post dose at Weeks 12 and 24]

   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.

10. Maximum Observed Concentration (Cmax) of GSK1278863 [1, 2, 3 and 4 hours post dose at Weeks 12 and 24]

    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.

11. Monthly Average Dose of Intravenous (IV) Iron During the Treatment Period [Up to Week 24]

    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).

12. Number of Participants Who Used Iron During the Treatment Period [Up to Week 24]

    The number of participants who used iron (both IV and oral iron) during the treatment period were summarized.

13. Change From Baseline in Ferritin [Baseline and up to Week 24]

    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.

14. Percent Change From Baseline in TSAT [Baseline and up to Week 24]

    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).

15. Percent Change From Baseline in Hepcidin [Baseline and up to Week 24]

    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).

16. Change From Baseline in Serum Iron [Baseline and up to Week 24]

    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.

17. Change From Baseline in Total Iron Binding Capacity (TIBC) [Baseline and up to Week 24]

    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.

18. Dose Level of GSK1278863 at Indicated Time Points [Up to Week 24]

    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.

19. Number of Participants With Frequency of Dose Adjustments [Up to Week 24]

    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).

20. Duration of Treatment Interruption Due to Hgb >13 g/dL [Up to Week 24]

    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

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

• Dialysis: Patients on hemodialysis (HD) or hemodiafiltration (HDF)

• Use of any erythropoiesis stimulating agent (ESA): Newly started dialysis (Dialysis newly started <12 weeks before screening): Patients not using ESAs after the start of dialysis; Maintenance dialysis (Dialysis started >=12 weeks before screening): Patients not using ESAs within 8 weeks before screening (including interruption of ESA therapy)

• Hemoglobin (Hgb): >=8.0 to <10.0 g/dL (measured using a point-of-care Hgb measurement device at the study site on Day 1)

• Iron parameter: Ferritin >100 nanograms (ng)/milliliter (mL) or transferrin saturation (TSAT) >20% (at screening only)

• Gender (at screening only): Female or male.

A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin [hCG] test for females of reproductive potential [FRP] only), not breastfeeding, and at least one of the following conditions applies:

• Females of non-reproductive potential defined as: Pre-menopausal with one of the following and no plans to utilise assisted reproductive techniques (example [e.g.], in vitro fertilisation or donor embryo transfer): documented bilateral tubal ligation or salpingectomy; documented hysteroscopic tube occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy

• Post-menopausal 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 simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause is confirmatory [the reference values are provided separately]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly 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 enrollment.

Females of reproductive potential who agree to follow one of the options listed in the "GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential" from 28 days before the first dose of study treatment until completion of the follow-up visit.

• Informed consent: Subjects who can provide written informed consent to the study, involving compliance with the requirements and patient responsibilities stated in the consent form and the protocol.

Exclusion Criteria:

CKD related criteria

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

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

• Other causes of anemia: Pernicious anemia, thalassaemia, sickle cell disease, or myelodysplastic syndrome

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

Cardiovascular disease-related criteria

• History of myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack: Diagnosed within 8 weeks before 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

• Corrected QT interval (QTc) (at screening only): QTc >500 milliseconds (msec), or QTc

530 msec in subject with bundle branch block. Note: Corrected QT interval using Bazett's formula (QTcB) (machine-read or manually) will be used.

Other disease-related criteria

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

• Alanine transaminase (ALT) >2x upper limit of normal (ULN)

• Bilirubin >1.5xULN (If bilirubin fractions are measured and direct bilirubin is <35%, isolated bilirubin >1.5xULN will be acceptable.)

• 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: The only exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated >=8 weeks before screening.

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

Concomitant medications and other study treatment-related criteria

• Iron medication: Planned use of any intravenous iron during the screening period or from Day 1 to Week 4.

Note:

• Patients on oral iron may be enrolled if the iron dose regimen is unchanged during the screening period and from Day 1 to Week 4.

• Patients on anti-hyperphosphatemia medication containing iron (e.g., ferric citrate hydrate) for at least 12 weeks before screening may be enrolled if the medication is continued during the screening and from Day 1 to Week 4.

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

• Drugs and dietary supplements: Current use of prohibited prescription drugs, non-prescription drugs, or dietary supplements or planned use of any of these drugs during the study period (prohibited drugs: strong cytochrome P450 (CYP)2C8 inducers and inhibitors)

• Exposure to any other investigational product: Use of an investigational product within the past 30 days or five half lives of that investigational product (whichever is longer).

• Prior treatment with GSK1278863: Prior treatment with GSK1278863 for >30 days General health-related criteria

• Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator 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	455-8530
2	GSK Investigational Site	Aichi		Japan	457-8511
3	GSK Investigational Site	Fukuoka		Japan	802-8555
4	GSK Investigational Site	Hokkaido		Japan	065-8611
5	GSK Investigational Site	Ibaraki		Japan	300-0028
6	GSK Investigational Site	Ibaraki		Japan	302-0022
7	GSK Investigational Site	Ibaraki		Japan	306-0433
8	GSK Investigational Site	Kagoshima		Japan	891-0105
9	GSK Investigational Site	Kumamoto		Japan	861-8520
10	GSK Investigational Site	Kyoto		Japan	613-0034
11	GSK Investigational Site	Mie		Japan	510-8101
12	GSK Investigational Site	Nagano		Japan	392-8510
13	GSK Investigational Site	Nagano		Japan	399-8292
14	GSK Investigational Site	Oita		Japan	870-0844
15	GSK Investigational Site	Osaka		Japan	555-0001
16	GSK Investigational Site	Shiga		Japan	523-0082
17	GSK Investigational Site	Yamagata		Japan	990-0834

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jul 19, 2017
• Statistical Analysis Plan - Nov 29, 2017

More Information

Publications

• Tsubakihara Y, Akizawa T, Nangaku M, Onoue T, Yonekawa T, Matsushita H, Endo Y, Cobitz A. A 24-Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients. Ther Apher Dial. 2020 Apr;24(2):108-114. doi: 10.1111/1744-9987.12962. Epub 2019 Aug 13.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02829320
• Other Study ID Numbers: 204716
• First Posted: Jul 12, 2016
• Last Update Posted: Dec 3, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: efficacy; hemodialysis (HD); hemoglobin (Hgb); erythropoiesis-stimulating agents (ESAs); GSK1278863
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	All Participants
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 Participants	28
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.5 (10.16)
Sex: Female, Male (Count of Participants)
Female	3 10.7%
Male	25 89.3%
Race/Ethnicity, Customized (Count of Participants) [Number]
Asian - Japanese Heritage	28 100%
Dialysis Status (Count of Participants)
Newly started dialysis	11 39.3%
Maintenance dialysis	17 60.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hgb at Week 4
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Mean (95% Confidence Interval) [G/dL]	0.79

2. Primary Outcome

Title	Number of Participants by Hgb Change From Baseline Category at Week 4
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
<= -2.0	0 0%
> -2.0 to -1.0	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%

3. Secondary Outcome

Title	Hgb Values at the Indicated Time Points
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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)
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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)
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Median (Inter-Quartile Range) [Days]	57.0

7. Secondary Outcome

Title	Number of Participants Who Had Hgb Level of Less Than 7.5 g/dL
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Count of Participants [Participants]	0 0%

8. Secondary Outcome

Title	Number of Participants Who Had Hgb Increase of More Than 2 g/dL Over Any 4 Weeks
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Count of Participants [Participants]	1 3.6%

9. Secondary Outcome

Title	Number of Participants Who Had Hgb Level of More Than 13.0 g/dL
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Count of Participants [Participants]	3 10.7%

10. Secondary Outcome

Title	Number of Episodes of Achieving Hgb Level of More Than 13.0 g/dL
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Number [Episodes]	7

11. Secondary Outcome

Title	Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863
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

Outcome Measure Data

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
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%.
Measure Participants	1	12	22	13	3	1	1
AUC (0-4), Week 12, n=0,4,14,8,1,0,0	25.7228 (289.9)	95.1319 (111.9)	200.6036 (62.9)	233.3933 (NA)
AUC (0-4), Week 24, n=1,8,8,5,2,1,1	43.3100 (NA)	33.8941 (230.9)	86.3702 (58.9)	133.3020 (50.9)	437.0983 (18.7)	749.4583 (NA)	126.2883 (NA)
AUC (0-4), All, n=1,12,22,13,3,1,1	43.3100 (NA)	30.9164 (225.3)	91.8474 (91.1)	171.4229 (60.8)	354.6083 (40.0)	749.4583 (NA)	126.2883 (NA)

12. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of GSK1278863
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

Outcome Measure Data

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
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%.
Measure Participants	1	12	22	13	3	1	1
Cmax, Week 12, n=0,4,14,8,1,0,0	13.9578 (340.6)	57.6572 (81.2)	122.9883 (56.9)	179.0000 (NA)
Cmax, Week 24, n=1,8,8,5,2,1,1	27.5000 (NA)	18.3448 (202.3)	44.8853 (49.8)	100.2261 (41.3)	202.9384 (3.5)	311.0000 (NA)	93.4000 (NA)
Cmax, All, n=1,12,22,13,3,1,1	27.5000 (NA)	16.7474 (217.4)	52.6391 (70.4)	113.6784 (50.4)	194.6229 (7.7)	311.0000 (NA)	93.4000 (NA)

13. Secondary Outcome

Title	Monthly Average Dose of Intravenous (IV) Iron During the Treatment Period
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Quarter 1; n= 3	231.61 (99.916)
Quarter 2; n= 4	217.19 (86.529)

14. Secondary Outcome

Title	Number of Participants Who Used Iron During the Treatment Period
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Week 4	-23.06
Week 12	-15.31
Week 24	-10.07

17. Secondary Outcome

Title	Percent Change From Baseline in Hepcidin
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Week 4, n=26	-64.78
Week 12, n=22	-61.74
Week 24, n=21	-55.67

18. Secondary Outcome

Title	Change From Baseline in Serum Iron
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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)
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
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
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Day 1	4.0
Week 4	4.0
Week 8	4.0
Week 12	4.0
Week 16	4.0
Week 20	4.0
Week 12 to 24	4.00

21. Secondary Outcome

Title	Number of Participants With Frequency of Dose Adjustments
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	28
Any dose adjustments	21 75%
Number of dose adjustments=0	7 25%
Number of dose adjustments=1	9 32.1%
Number of dose adjustments=2	7 25%
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%

22. Secondary Outcome

Title	Duration of Treatment Interruption Due to Hgb >13 g/dL
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

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	All Participants
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%.
Measure Participants	3
Median (Full Range) [Days]	84

Adverse Events

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
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 (%)	# Events
Total	0/28 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	3/28 (10.7%)
Injury, poisoning and procedural complications
Shunt occlusion	2/28 (7.1%)	3
Product Issues
Device dislocation	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	12/28 (42.9%)
Infections and infestations
Nasopharyngitis	9/28 (32.1%)	10
Infected dermal cyst	2/28 (7.1%)	3
Injury, poisoning and procedural complications
Shunt stenosis	2/28 (7.1%)	2

Limitations/Caveats

[Not Specified]

More Information

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.