Trial Outcomes & Findings for A Study to Evaluate Safety and Efficacy of GSK1278863 in Non-Dialysis Dependent (NDD) Subjects With Anemia Associated With Chronic Kidney Diseases (CKD) (NCT NCT01977573)

NCT ID: NCT01977573

Last Updated: 2018-10-12

Results Overview

The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. The primary objective was to characterize the ability of GSK1278863 to achieve mean Hgb response within the target range.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

252 participants

Primary outcome timeframe

Week 24

Results posted on

2018-10-12

Participant Flow

Two groups of participants(par.) were enrolled in this study. Group 1 consisted of recombinant human erythropoietin(rhEPO)-naive par. whereas Group 2 consisted of rhEPO users.

Post screening, eligible par. were randomized to receive either GSK1278863 once a day (QD) or to the Control arm in a 3:1 fashion in Group 1 and 1:1 fashion in Group 2.

Participant milestones

Participant milestones
Measure	rhEPO-Naive GSK1278863 RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Overall Study STARTED	136	44	36	36
Overall Study COMPLETED	116	41	32	33
Overall Study NOT COMPLETED	20	3	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	rhEPO-Naive GSK1278863 RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Overall Study Adverse Event	7	0	2	1
Overall Study Lost to Follow-up	1	0	0	1
Overall Study Physician Decision	1	0	0	0
Overall Study Protocol Violation	3	1	0	0
Overall Study Reached Defined Stopping Criteria	2	1	1	0
Overall Study Withdrawal by Subject	6	1	1	1

Baseline Characteristics

A Study to Evaluate Safety and Efficacy of GSK1278863 in Non-Dialysis Dependent (NDD) Subjects With Anemia Associated With Chronic Kidney Diseases (CKD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=43 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=33 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=36 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.	Total n=235 Participants Total of all reporting groups
Age, Continuous	67.6 Years STANDARD_DEVIATION 12.21 • n=5 Participants	64.3 Years STANDARD_DEVIATION 14.22 • n=7 Participants	62.0 Years STANDARD_DEVIATION 14.06 • n=5 Participants	66.7 Years STANDARD_DEVIATION 12.89 • n=4 Participants	66.1 Years STANDARD_DEVIATION 13.04 • n=21 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	23 Participants n=7 Participants	17 Participants n=5 Participants	23 Participants n=4 Participants	138 Participants n=21 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	20 Participants n=7 Participants	16 Participants n=5 Participants	13 Participants n=4 Participants	97 Participants n=21 Participants
Race/Ethnicity, Customized African American/African Heritage	14 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	22 Participants n=21 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Japanese/East Asian/South East Asian Heritage	28 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	12 Participants n=4 Participants	60 Participants n=21 Participants
Race/Ethnicity, Customized White	81 Participants n=5 Participants	30 Participants n=7 Participants	22 Participants n=5 Participants	19 Participants n=4 Participants	152 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-Treat (ITT): The ITT population consisted of all randomized participants who received at least one dose of study drug, had a Baseline and at least one corresponding on-treatment assessment. Only participants who were available at the indicated time point were analyzed.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=43 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=33 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=36 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Summary of Hemoglobin (Hgb) Concentration at Week 24 Original n=45,15,19,13	10.20 grams per deciliter Standard Deviation 0.906	10.64 grams per deciliter Standard Deviation 0.664	10.03 grams per deciliter Standard Deviation 0.522	10.66 grams per deciliter Standard Deviation 0.620
Summary of Hemoglobin (Hgb) Concentration at Week 24 Amended n=61,21,11,17	10.96 grams per deciliter Standard Deviation 1.044	11.05 grams per deciliter Standard Deviation 1.144	10.42 grams per deciliter Standard Deviation 0.827	10.86 grams per deciliter Standard Deviation 1.182

SECONDARY outcome

Timeframe: Week 24

Population: ITT population. Only participants who were available at the indicated time point were analyzed.

Target range is defined as: Original Hgb Criteria of 9.0 to 10.5 gram/deciliter (g/dL), and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	78 participants	20 participants	22 participants	19 participants

SECONDARY outcome

Timeframe: Over a period of 24 Weeks

Population: ITT population.

The Hgb stopping criteria was a value of \<7.5 mg/dL obtained on-site via a validated point-of-care Hgb measurement device, which necessitated permanent discontinuation of the study medication. None of the participants met the stopping criteria therefore there is no data to present for this outcome measure.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=136 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=44 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=36 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=36 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants Reaching Pre-defined Hgb Stopping Criteria	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Intent-to-Treat (ITT) population consisted all randomized participants who received at least one dose of study drug, had a Baseline and at least one corresponding on-treatment assessment. Only participants with available hepcidin values at Baseline and Week 24 were analyzed.

Baseline is the last pre-dose hepcidin value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the Week 24 value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=35 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=29 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Percent Change From Baseline in Hepcidin Concentration at Week 24	-19.27 percent change in Hepcidin Interval -28.1 to -9.36	6.67 percent change in Hepcidin Interval -13.62 to 31.72	-9.87 percent change in Hepcidin Interval -28.59 to 13.76	-17.12 percent change in Hepcidin Interval -33.22 to 2.86

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: ITT population. Only participants having a Baseline EPO measurement and at least one post-baseline EPO measurement were analyzed.

Blood samples for control arm were collected pre-dose for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm. Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-baseline values minus the Baseline value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=42 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=33 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=36 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)	7.27 International Units per liter Standard Deviation 12.744	27.05 International Units per liter Standard Deviation 94.999	3.69 International Units per liter Standard Deviation 20.554	25.85 International Units per liter Standard Deviation 38.890

SECONDARY outcome

Timeframe: Baseline and up to Week 24

Population: ITT population. Only participants with data available at Baseline and a maximum observed change were analyzed.

Blood samples for control arm were collected pre-dose for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for VEGF measurement. The maximum observed change from baseline in VEGF was recorded for each arm . Baseline value for VEGF is the pre-dose value on Day 1. Change from Baseline in VEGF was calculated as the individual post-baseline values minus the Baseline value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=42 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=33 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=36 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)	76.36 percent change in VEGF concentration Interval 59.46 to 95.06	26.84 percent change in VEGF concentration Interval 1.73 to 58.15	49.99 percent change in VEGF concentration Interval 28.28 to 75.39	40.85 percent change in VEGF concentration Interval 19.14 to 66.52

SECONDARY outcome

Timeframe: Weeks 12 to 24

Population: ITT population. Only participants with data available at specific time points were analyzed.

The number of days a participant's Hgb was within target range was calculated by estimating (using linear interpolation) the number of days within target range between two scheduled Hgb visits. Percentage of time within range for a participant was calculated by dividing the total number of days that Hgb was within range during Weeks 12 to 24 by the total number of days the participant remained on treatment during Weeks 12 to 24. Similary, percent of time above and below Hgb target range was calculated. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=112 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=38 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=32 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24 Percentage of time within target range	68.99 percentage of days Standard Deviation 34.612	51.01 percentage of days Standard Deviation 41.403	75.06 percentage of days Standard Deviation 32.485	61.29 percentage of days Standard Deviation 43.352
Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24 Percentage of time above target range	22.84 percentage of days Standard Deviation 33.825	45.10 percentage of days Standard Deviation 42.579	17.96 percentage of days Standard Deviation 28.809	31.10 percentage of days Standard Deviation 41.683
Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24 Percentage of time below target range	8.17 percentage of days Standard Deviation 20.301	3.89 percentage of days Standard Deviation 16.175	6.98 percentage of days Standard Deviation 21.118	7.61 percentage of days Standard Deviation 25.113

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific time point were analyzed.

Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=108 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Ferritin Concentration at Week 24	-30.8 micrograms per liter Standard Deviation 110.50	-2.4 micrograms per liter Standard Deviation 77.06	-63.4 micrograms per liter Standard Deviation 141.93	-20.4 micrograms per liter Standard Deviation 63.38

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific time point were analyzed.

Baseline is the last pre-dose transferrin value. Change from Baseline in transferrin was calculated by subtracting the Baseline value from the Week 24 value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=107 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Transferrin Concentration at Week 24	0.077 grams per liter Standard Deviation 0.3577	-0.008 grams per liter Standard Deviation 0.2694	0.171 grams per liter Standard Deviation 0.4124	0.018 grams per liter Standard Deviation 0.2395

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific time point were analyzed.

Transferrin saturation is measured as a percentage; it is a ratio of serum iron and total iron-binding capacity. Baseline is the last pre-dose transferrin saturation value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the post-dose value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=35 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Percent Change From Baseline in Transferrin Saturation at Week 24	-1.1 percent change Interval -8.0 to 6.4	12.3 percent change Interval 2.2 to 23.3	-15.7 percent change Interval -26.8 to -3.0	11.4 percent change Interval -14.7 to 45.6

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with available total iron values at Baseline and Week 24 were analyzed.

Baseline is the last pre-dose total iron value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=107 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Total Iron at Week 24	1.0 micromoles per liter Standard Deviation 5.01	2.5 micromoles per liter Standard Deviation 5.98	-1.8 micromoles per liter Standard Deviation 5.54	0.7 micromoles per liter Standard Deviation 8.36

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific timepoint were analyzed.

TIBC measures the blood's capacity to bind iron with transferrin. Baseline is the last pre-dose TIBC value. Change from Baseline in TIBC was calculated by subtracting the Baseline value from the Week 24 value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=35 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24	3.2 micromoles per liter Standard Deviation 6.46	0.1 micromoles per liter Standard Deviation 5.17	3.0 micromoles per liter Standard Deviation 9.44	-1.0 micromoles per liter Standard Deviation 6.69

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific time point were analyzed.

Reticulocytes are slightly immature red blood cells. Reticulocyte Hgb content is used to differentiate iron deficiency from other causes of anemia. Baseline is the last pre-dose CHr value. Change from Baseline in reticulocyte Hgb was calculated by subtracting the Baseline value from the post-dose value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=108 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=35 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24	-0.19 picogram Standard Deviation 1.109	-0.33 picogram Standard Deviation 1.085	-0.32 picogram Standard Deviation 0.864	-0.19 picogram Standard Deviation 1.546

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific timepoint were analyzed.

Baseline is the last pre-dose hematocrit value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=111 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Hematocrit at Week 24	2.64 percentage change in Fraction of 1 Standard Deviation 3.389	3.13 percentage change in Fraction of 1 Standard Deviation 3.245	-0.66 percentage change in Fraction of 1 Standard Deviation 3.074	2.09 percentage change in Fraction of 1 Standard Deviation 3.243

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific time point were analyzed.

Baseline is the last pre-dose red blood cell count. Change from Baseline in red blood cell count was calculated by subtracting the Baseline count from the post-dose count.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=111 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Red Blood Cell Count at Week 24	0.28 10^12 cells per liter Standard Deviation 0.377	0.34 10^12 cells per liter Standard Deviation 0.365	-0.08 10^12 cells per liter Standard Deviation 0.312	0.22 10^12 cells per liter Standard Deviation 0.318

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population. Only participants with data available at specific timepoint were analyzed.

Reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline is the last pre-dose red reticulocyte count. Change from Baseline in reticulocyte cell count was calculated by subtracting the Baseline count from the Week 24 count.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=111 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=31 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Change From Baseline in Reticulocyte Cell Count at Week 24	-0.02 percentage of reticulocytes Standard Deviation 0.551	-0.12 percentage of reticulocytes Standard Deviation 0.648	0.27 percentage of reticulocytes Standard Deviation 0.892	-0.09 percentage of reticulocytes Standard Deviation 0.755

SECONDARY outcome

Timeframe: Day 1 (pre-dose), Week (Wk) 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose)

Population: Pharmacokinetics (PK) population: All participants from whom a PK sample was obtained and analyzed. This population did not include participants from the control groups.

Blood samples were collected for individual plasma GSK1278863 and metabolite (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531401, and GSK2531403) concentration measurement on Day 1 (pre-dose), Wk 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose). Participants available in each arm at the specified time points have been presented.

Outcome measures

SECONDARY outcome

Timeframe: From Week 4 up to 24 Weeks

Population: Intent-to-Treat population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed.

After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=102 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=26 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Mean Number of Dose Adjustments up to 24 Weeks	1.8 number of adjustments Standard Deviation 0.82	1.7 number of adjustments Standard Deviation 0.72	—	—

SECONDARY outcome

Timeframe: From week 4 up to 24 weeks

Population: Intent-to-Treat population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=102 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=26 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency Once	39 participants	11 participants	—	—
Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency Twice	50 participants	11 participants	—	—
Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency Thrice	8 participants	4 participants	—	—
Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency Four times	4 participants	0 participants	—	—
Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency Five times or more	1 participants	0 participants	—	—

SECONDARY outcome

Timeframe: From Week 4 up to Week 20

Population: ITT population. Only those participants with at least one dose adjustment of GSK1278863 were analyzed.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=102 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=26 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 Week 16	30 Participants	6 Participants	—	—
Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 Week 12	30 Participants	7 Participants	—	—
Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 Week 4	78 Participants	21 Participants	—	—
Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 Week 8	24 Participants	6 Participants	—	—
Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20 Week 20	22 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 Weeks

Population: ITT population.

The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=33 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks	249.75 milligrams Standard Deviation 186.921	320.42 milligrams Standard Deviation 214.865	—	—

SECONDARY outcome

Timeframe: Up to 24 Weeks

Population: ITT population.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=33 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Mean Final Dose of GSK1278863 up to 24 Weeks	1.75 milligrams per day Standard Deviation 1.809	1.86 milligrams per day Standard Deviation 1.692	—	—

SECONDARY outcome

Timeframe: Up to 24 Weeks.

Population: Completers Population: ITT participants who fully completed study without prematurely discontinuing study drug. Only participants with Hgb excursions were analyzed.

A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter. Hgb cycle is calculated as two consecutive Hgb excursions in different directions.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=23 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=10 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=4 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=8 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Hemoglobin (Hgb) Excursions	26 number of excursions	10 number of excursions	4 number of excursions	9 number of excursions

SECONDARY outcome

Timeframe: Up to 24 Weeks

Population: Completers population. Only participants with Hgb cycles were analyzed.

A Hgb cycle is calculated as two consecutive Hgb excursions in different directions. A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=3 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Hemoglobin (Hgb) Cycles up to 24 Weeks	3 number of Hgb cycles	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Completers population. Only participants in the GSK1278863 arms with dose cycles were analyzed.

A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease).

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=1 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Dose Cycles up to 24 Weeks	1 number	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Completers population.

A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.	23 participants	10 participants	4 participants	8 participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Completers population.

A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter. A Hgb cycle is two consecutive Hgb excursions in different directions.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=36 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=30 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=30 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks	3 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Completers population. Only participants in the GSK1278863 arms with dose cycles were analyzed.

A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease). participants

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=106 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=30 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants With at Least One Dose Cycle up to 24 Weeks	1 participants	0 participants	—	—

SECONDARY outcome

Timeframe: From Day 1 up to Week 28

Population: ITT Population

Participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO any time Post Baseline were analyzed. RhEPO was not applicable for the control arms since it was a planned therapy in those arms, hence presented as NA. (EudraCT only: A value of 99999 is used where no data is available or NA.)

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=43 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 n=33 Participants RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control n=36 Participants RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline Blood Transfusions	3 participants	1 participants	1 participants	0 participants
Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline IV Iron	20 participants	3 participants	3 participants	4 participants
Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline Inadvertent rhEPO use	4 participants	NA participants Non-rhEPO users were not evaluated for this data point.	9 participants	NA participants Non-rhEPO users were not evaluated for this data point.
Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline Rescue rhEPO	1 participants	NA participants Non-rhEPO users were not evaluated for this data point.	0 participants	NA participants Non-rhEPO users were not evaluated for this data point.

SECONDARY outcome

Timeframe: From Week 4 up to Week 24

Population: ITT population.

Number of Weeks dose was withheld because hemoglobin exceed the upper limit is presented as the number of participants with withheld dose during the time periods categorized by Weeks.

Outcome measures

Outcome measures
Measure	rhEPO-Naive GSK1278863 n=123 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=33 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit 0 Weeks	102 participants	30 participants	—	—
Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit >0-4 Weeks	4 participants	2 participants	—	—
Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit >4-8 Weeks	8 participants	0 participants	—	—
Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit >8-12 Weeks	8 participants	0 participants	—	—
Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit >12 Weeks	1 participants	0 participants	—	—

Adverse Events

rhEPO-Naive GSK1278863

Serious events: 23 serious events

Other events: 47 other events

Deaths: 0 deaths

rhEPO-Naive Control

Serious events: 7 serious events

Other events: 14 other events

Deaths: 0 deaths

rhEPO-User GSK1278863

Serious events: 7 serious events

Other events: 20 other events

Deaths: 0 deaths

rhEPO-User Control

Serious events: 7 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	rhEPO-Naive GSK1278863 n=134 Participants RhEPO-naive participants were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863, and returned for the follow-up visit at Week 28.	rhEPO-Naive Control n=35 Participants RhEPO-naive participants were randomly assigned to receive open-label rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator's clinical judgment, for 24 weeks. At Week 24, participants stopped taking rhEPO (if applicable) and remained off rhEPO or other Erythropoiesis Stimulating Agents (ESA) until at least the follow-up visit at Week 28.	rhEPO-User GSK1278863 RhEPO users were randomly assigned to receive GSK1278863 QD for 24 weeks. Participants were blinded to the dose-level they received throughout the study. At Week 24, participants stopped taking GSK1278863 and did not re-start rhEPO or other ESAs until after the follow-up visit at Week 28 (except in cases where there was a compelling clinical reason \[based on Investigator's opinion\] to start rhEPO therapy).	rhEPO-User Control RhEPO users were randomly assigned to receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, based on the Investigator clinical judgment, for 24 weeks. Participants were allowed to continue rhEPO therapy between Week 24 and 28.
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 4, 7-13 hour Post-Dose, n=117, 31	2.3 nanograms per milliliter Standard Deviation 7.06	0.8 nanograms per milliliter Standard Deviation 1.22	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.1 nanograms per milliliter Standard Deviation 5.67	3.2 nanograms per milliliter Standard Deviation 2.43	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 20, 1 hour Post-Dose, n=110, 28	2.1 nanograms per milliliter Standard Deviation 3.52	1.6 nanograms per milliliter Standard Deviation 1.39	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 20, 3 hour Post-Dose, n=109, 29	4.5 nanograms per milliliter Standard Deviation 5.43	4.7 nanograms per milliliter Standard Deviation 3.53	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.2 nanograms per milliliter Standard Deviation 3.87	1.0 nanograms per milliliter Standard Deviation 0.96	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 4, 7-13 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter Standard Deviation 4.11	0.7 nanograms per milliliter Standard Deviation 0.70	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter Standard Deviation 4.48	0.6 nanograms per milliliter Standard Deviation 0.66	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 20, 3 hour Post-Dose, n=109, 29	3.1 nanograms per milliliter Standard Deviation 4.07	3.1 nanograms per milliliter Standard Deviation 2.56	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 4, 8-14 hour Post-Dose, n=116, 31	0.9 nanograms per milliliter Standard Deviation 1.19	1.0 nanograms per milliliter Standard Deviation 0.61	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.9 nanograms per milliliter Standard Deviation 1.29	1.1 nanograms per milliliter Standard Deviation 0.69	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 20, 1 hour Post-Dose, n=110, 28	0.6 nanograms per milliliter Standard Deviation 0.88	0.5 nanograms per milliliter Standard Deviation 0.40	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 20, 2 hour Post-Dose, n=109, 29	0.9 nanograms per milliliter Standard Deviation 1.15	1.0 nanograms per milliliter Standard Deviation 0.71	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 20, 3 hour Post-Dose, n=109, 29	1.1 nanograms per milliliter Standard Deviation 1.25	1.2 nanograms per milliliter Standard Deviation 0.88	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.2 nanograms per milliliter Standard Deviation 2.50	1.2 nanograms per milliliter Standard Deviation 0.99	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 20, 1 hour Post-Dose, n=110, 28	0.8 nanograms per milliliter Standard Deviation 1.53	0.6 nanograms per milliliter Standard Deviation 0.54	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 20, 2 hour Post-Dose, n=109, 29	1.6 nanograms per milliliter Standard Deviation 2.31	1.5 nanograms per milliliter Standard Deviation 1.22	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.00	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 4, 6-12 hour Post-Dose, n=116, 31	2.8 nanograms per milliliter Standard Deviation 4.00	4.3 nanograms per milliliter Standard Deviation 2.55	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 4, 7-13 hour Post-Dose, n=117, 31	2.7 nanograms per milliliter Standard Deviation 3.58	4.0 nanograms per milliliter Standard Deviation 2.29	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.7 nanograms per milliliter Standard Deviation 3.74	3.8 nanograms per milliliter Standard Deviation 2.31	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 4, 9-15 hour Post-Dose, n=116, 31	2.5 nanograms per milliliter Standard Deviation 3.53	3.8 nanograms per milliliter Standard Deviation 2.29	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 4, 9-15 hour Post-Dose, n=116, 31	2.6 nanograms per milliliter Standard Deviation 4.89	3.1 nanograms per milliliter Standard Deviation 2.76	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 20, Pre-Dose, n=111, 29	1.0 nanograms per milliliter Standard Deviation 2.06	0.8 nanograms per milliliter Standard Deviation 0.98	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 20, 2 hour Post-Dose, n=109, 29	3.8 nanograms per milliliter Standard Deviation 5.08	3.7 nanograms per milliliter Standard Deviation 2.98	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.00	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.9 nanograms per milliliter Standard Deviation 4.09	0.8 nanograms per milliliter Standard Deviation 1.16	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 20, Pre-Dose, n=111, 29	0.2 nanograms per milliliter Standard Deviation 0.56	0.1 nanograms per milliliter Standard Deviation 0.31	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 20, 1 hour Post-Dose, n=110, 28	1.4 nanograms per milliliter Standard Deviation 3.07	1.0 nanograms per milliliter Standard Deviation 1.09	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2487818, Wk 20, 2 hour Post-Dose, n=109, 29	2.8 nanograms per milliliter Standard Deviation 4.28	2.7 nanograms per milliliter Standard Deviation 2.21	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.00	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter Standard Deviation 1.30	1.2 nanograms per milliliter Standard Deviation 0.65	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.0 nanograms per milliliter Standard Deviation 1.51	1.1 nanograms per milliliter Standard Deviation 0.61	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2506102, Wk 20, Pre-Dose, n=111, 29	0.4 nanograms per milliliter Standard Deviation 0.73	0.4 nanograms per milliliter Standard Deviation 0.42	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.01	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.3 nanograms per milliliter Standard Deviation 2.06	1.4 nanograms per milliliter Standard Deviation 1.08	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter Standard Deviation 2.01	1.1 nanograms per milliliter Standard Deviation 0.93	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter Standard Deviation 2.10	1.2 nanograms per milliliter Standard Deviation 1.12	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 20, Pre-Dose, n=111, 29	0.3 nanograms per milliliter Standard Deviation 0.87	0.3 nanograms per milliliter Standard Deviation 0.38	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531398, Wk 20, 3 hour Post-Dose, n=109, 29	2.0 nanograms per milliliter Standard Deviation 2.42	2.0 nanograms per milliliter Standard Deviation 1.57	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 20, Pre-Dose, n=111, 29	1.3 nanograms per milliliter Standard Deviation 2.41	1.4 nanograms per milliliter Standard Deviation 1.38	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 20, 1 hour Post-Dose, n=110, 28	1.6 nanograms per milliliter Standard Deviation 2.65	1.6 nanograms per milliliter Standard Deviation 1.29	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 20, 2 hour Post-Dose, n=109, 29	2.3 nanograms per milliliter Standard Deviation 3.14	2.5 nanograms per milliliter Standard Deviation 1.85	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531401, Wk 20, 3 hour Post-Dose, n=109, 29	2.8 nanograms per milliliter Standard Deviation 3.50	3.2 nanograms per milliliter Standard Deviation 2.22	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.00	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.00	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 4, 6-12 hour Post-Dose, n=116, 31	2.0 nanograms per milliliter Standard Deviation 5.18	1.1 nanograms per milliliter Standard Deviation 1.69	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.6 nanograms per milliliter Standard Deviation 4.93	1.6 nanograms per milliliter Standard Deviation 5.49	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.4 nanograms per milliliter Standard Deviation 4.52	1.6 nanograms per milliliter Standard Deviation 4.60	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 20, Pre-Dose, n=111, 29	0.6 nanograms per milliliter Standard Deviation 3.07	0.3 nanograms per milliliter Standard Deviation 0.92	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 20, 1 hour Post-Dose, n=110, 28	22.8 nanograms per milliliter Standard Deviation 35.93	19.8 nanograms per milliliter Standard Deviation 19.66	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 20, 2 hour Post-Dose, n=109, 29	17.0 nanograms per milliliter Standard Deviation 28.57	19.4 nanograms per milliliter Standard Deviation 21.92	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK1278863, Wk 20, 3 hour Post-Dose, n=109, 29	11.6 nanograms per milliliter Standard Deviation 19.56	13.9 nanograms per milliliter Standard Deviation 19.12	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter Standard Deviation 0.00	0.0 nanograms per milliliter Standard Deviation 0.00	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.2 nanograms per milliliter Standard Deviation 5.21	3.7 nanograms per milliliter Standard Deviation 2.89	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2391220, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.8 nanograms per milliliter Standard Deviation 5.01	2.9 nanograms per milliliter Standard Deviation 2.54	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.7 nanograms per milliliter Standard Deviation 5.43	4.5 nanograms per milliliter Standard Deviation 3.14	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.5 nanograms per milliliter Standard Deviation 5.27	3.9 nanograms per milliliter Standard Deviation 2.56	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 4, 8-14 hour Post-Dose, n=116, 31	3.4 nanograms per milliliter Standard Deviation 5.68	3.7 nanograms per milliliter Standard Deviation 2.72	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 4, 9-15 hour Post-Dose, n=116, 31	3.2 nanograms per milliliter Standard Deviation 5.42	3.8 nanograms per milliliter Standard Deviation 3.01	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 20, Pre-Dose, n=111, 29	1.4 nanograms per milliliter Standard Deviation 2.65	1.2 nanograms per milliliter Standard Deviation 1.25	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 20, 1 hour Post-Dose, n=110, 28	2.3 nanograms per milliliter Standard Deviation 3.69	1.9 nanograms per milliliter Standard Deviation 1.38	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 20, 2 hour Post-Dose, n=109, 29	3.9 nanograms per milliliter Standard Deviation 5.03	3.8 nanograms per milliliter Standard Deviation 2.95	—	—
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint GSK2531403, Wk 20, 3 hour Post-Dose, n=109, 29	4.7 nanograms per milliliter Standard Deviation 5.43	4.9 nanograms per milliliter Standard Deviation 3.75	—	—