Trial Outcomes & Findings for 4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease (NCT NCT01587924)

NCT ID: NCT01587924

Last Updated: 2017-11-14

Results Overview

Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 80 participants
• Primary outcome timeframe: Baseline (pre-dose on Day 1) and up to week 4
• Results posted on: 2017-11-14

Participant Flow

This study was conducted in hemodialysis-dependent (HDD) participants from 06 June 2012 till 17 June 2013 across 48 centers in the United States (US), Canada, and European Union. A total of 68 participants were planned to be enrolled.

A total of 103 participants were screened, out of which 83 participants were randomized in the study. The participants were receiving recombinant human erythropoietin (rhEPO) for 2 weeks and had hemoglobin (hgb) range of 9.5 to 12.0 gram per deciliter (g/dL); however, one participant did not receive the study drug.

Participant milestones

Measure	0.5 mg GSK1278863 Eligible participants received oral GK1278863 0.5 milligrams (mg) once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Overall Study STARTED	21	21	21	20
Overall Study COMPLETED	17	17	17	19
Overall Study NOT COMPLETED	4	4	4	1

Reasons for withdrawal

Measure	0.5 mg GSK1278863 Eligible participants received oral GK1278863 0.5 milligrams (mg) once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Overall Study Adverse Event	0	2	0	0
Overall Study Protocol Violation	2	1	2	1
Overall Study Met Hemoglobin stopping criteria	2	0	1	0
Overall Study Withdrawal by Subject	0	1	1	0

Baseline Characteristics

4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease

Baseline characteristics by cohort

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks	Total n=80 Participants Total of all reporting groups
Age, Continuous	56.4 Years STANDARD_DEVIATION 16.80 • n=5 Participants	54.7 Years STANDARD_DEVIATION 18.78 • n=7 Participants	55.9 Years STANDARD_DEVIATION 18.37 • n=5 Participants	64.2 Years STANDARD_DEVIATION 12.77 • n=4 Participants	57.8 Years STANDARD_DEVIATION 16.92 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	16 Participants n=4 Participants	58 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	18 Participants n=21 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	54 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to week 4

Population: ITT population. Only those participants available at the specified time points were analyzed.

Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.

Outcome measures

Measure	0.5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment	-1.130 Grams per deciliter (g/dL) Standard Deviation 0.6830	-1.070 Grams per deciliter (g/dL) Standard Deviation 0.7703	0.212 Grams per deciliter (g/dL) Standard Deviation 0.7521	-0.273 Grams per deciliter (g/dL) Standard Deviation 0.6335

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Within participant standard deviation for Hgb acts as a measure of Hgb variability. Hgb of participants was recorded over 4 weeks.

Outcome measures

Measure	0.5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Hgb Variability Over 4 Weeks	0.53 g/dL Standard Deviation 0.271	0.55 g/dL Standard Deviation 0.325	0.40 g/dL Standard Deviation 0.364	0.35 g/dL Standard Deviation 0.193

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from baseline for hepcidin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Adjusted mean change from Baseline is presented as Least square (LS) mean.

Outcome measures

Measure	0.5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=18 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Evaluation of Change From Baseline in Hepcidin Over Period	204.88 Micrograms per liter (mcg/L) Standard Error 60.741	150.29 Micrograms per liter (mcg/L) Standard Error 62.619	16.42 Micrograms per liter (mcg/L) Standard Error 62.815	-45.47 Micrograms per liter (mcg/L) Standard Error 61.939

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline for hsCRP was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Peak change from Baseline also was calculated; however adjusted mean change from Baseline has been presented here as LS means.

Outcome measures

Measure	0.5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks	-0.40 Milligrams per liter (mg/L) Standard Error 1.784	-4.76 Milligrams per liter (mg/L) Standard Error 1.834	-1.48 Milligrams per liter (mg/L) Standard Error 1.886	-2.92 Milligrams per liter (mg/L) Standard Error 1.784

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline (pre-dose on Day 1) for EPO was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the pre-dose Day 1 value. Adjusted means are presented as LS means.

Outcome measures

Measure	0.5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=16 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Change From Baseline for Erythropoeitin (EPO) Over Period	4.368 Units per liter (U/L) Standard Error 73.3485	3.263 Units per liter (U/L) Standard Error 73.5023	181.948 Units per liter (U/L) Standard Error 77.7763	393.159 Units per liter (U/L) Standard Error 71.4855

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline for peak VEGF was analyzed up to 4 weeks. Baseline assessment was performed pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Absolute mean change and peak change from Baseline in peak VGEF were also calculated; however, only model adjusted peak change in peak VGEF from Baseline has been presented as LS means.

Outcome measures

Measure	0.5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=17 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks	23.21 Nanograms per liter (ng/L) Standard Error 12.110	21.52 Nanograms per liter (ng/L) Standard Error 12.291	53.85 Nanograms per liter (ng/L) Standard Error 12.645	20.59 Nanograms per liter (ng/L) Standard Error 12.874

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline for hematocrit over 4 weeks was performed. Change from Baseline is the value at indicated time point minus the Baseline value.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks Week 1	-0.59 Percentage Standard Deviation 1.609	-0.16 Percentage Standard Deviation 1.823	-0.75 Percentage Standard Deviation 1.735	0.20 Percentage Standard Deviation 1.738
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks Week 2	-1.33 Percentage Standard Deviation 2.122	-1.56 Percentage Standard Deviation 2.296	-0.75 Percentage Standard Deviation 1.960	2.02 Percentage Standard Deviation 8.248
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks Week 3	-2.32 Percentage Standard Deviation 2.634	-2.22 Percentage Standard Deviation 2.712	-0.65 Percentage Standard Deviation 2.277	0.24 Percentage Standard Deviation 2.507
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks Week 4	-3.22 Percentage Standard Deviation 2.731	-2.63 Percentage Standard Deviation 3.006	-0.33 Percentage Standard Deviation 2.044	-0.22 Percentage Standard Deviation 2.874

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Residual standard deviation was derived by linear regression. Hgb of participants was recorded over 4 weeks

Outcome measures

Measure	0.5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Residual Standard Deviation in Hgb (From the Linear Regression)	0.24 g/L Standard Deviation 0.108	0.26 g/L Standard Deviation 0.115	0.26 g/L Standard Deviation 0.309	0.20 g/L Standard Deviation 0.112

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Time spent with Hgb within range (where range was defined as +-0.5 g/dL and +-1 g/dL from baseline Hgb ) was analyzed. Baseline value of Hgb was recorded pre-dose on Day 1.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb Within +/- 0.5 g/dL	12.82 Days Interval 6.98 to 21.85	14.34 Days Interval 4.86 to 25.76	24.41 Days Interval 8.94 to 28.0	21.15 Days Interval 10.5 to 28.0
Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb Within +/- 1 g/dL	27.71 Days Interval 19.25 to 28.0	20.79 Days Interval 12.76 to 28.0	28.00 Days Interval 24.77 to 28.0	28.00 Days Interval 23.33 to 28.0

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and Week 4

Population: ITT population. Only those participants available at the specified time points were analyzed.

Change from Baseline (pre-dose on Day 1) in ferritin over 4 weeks was analyzed. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.

Outcome measures

Measure	0.5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks	76.7 Micrograms per liter Standard Error 36.31	-1.6 Micrograms per liter Standard Error 37.41	-76.7 Micrograms per liter Standard Error 38.48	-38.0 Micrograms per liter Standard Error 37.27

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and Week 4

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline for ferritin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.

Outcome measures

Measure	0.5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks	0.105 Grams per liter Standard Error 0.0699	0.155 Grams per liter Standard Error 0.0719	0.221 Grams per liter Standard Error 0.0737	0.059 Grams per liter Standard Error 0.0703

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and Week 4

Population: ITT population. Only those participants available at the specified time points were analyzed..

Transferrin saturation is a medical laboratory test and is the ratio of serum iron and total iron-binding capacity, multiplied by 100 and expressed as a ratio. Evaluation of change from baseline for transferrin saturation was performed up to 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1. Model adjusted mean values are presented as LS mean values.

Outcome measures

Measure	0.5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks	6.4 Ratio Standard Error 3.33	11.7 Ratio Standard Error 3.34	1.3 Ratio Standard Error 3.42	-0.1 Ratio Standard Error 3.24

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and at Week 4

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline for total iron was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Adjusted mean was presented as LS mean.

Outcome measures

Measure	0.5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks	4.3 Micromoles per Liter Standard Error 1.44	6.2 Micromoles per Liter Standard Error 1.47	2.5 Micromoles per Liter Standard Error 1.51	0.3 Micromoles per Liter Standard Error 1.43

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and Week 4

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline in total iron binding capacity was performed over 4 weeks. Baseline was recorded pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Adjusted means are presented as LS means.

Outcome measures

Measure	0.5 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=18 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=17 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks	3.2 Micromoles per Liter Standard Error 1.05	3.7 Micromoles per Liter Standard Error 1.06	5.2 Micromoles per Liter Standard Error 1.08	1.3 Micromoles per Liter Standard Error 1.03

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Change from Baseline in RBCs was a pharmacodynamic (PD) biomarker. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Change from Baseline (pre-dose on Day 1) in RBCs was calculated over 4 weeks.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks Week 1	-0.04 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.157	-0.03 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.189	-0.06 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.184	0.02 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.177
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks Week 2	-0.13 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.191	-0.14 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.243	-0.05 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.210	0.18 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.771
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks Week 3	-0.22 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.248	-0.19 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.305	-0.05 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.229	0.01 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.256
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks Week 4	-0.29 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.259	-0.25 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.337	-0.03 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.198	-0.03 10^12 cells per Liter (Giga cells per L) Standard Deviation 0.262

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

Population: ITT population. Only those participants available at the specified time points were analyzed.

Evaluation of change from Baseline for reticulocytes was a PD parameter. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks Week 1	-0.42 Percentage change Standard Deviation 0.966	-0.56 Percentage change Standard Deviation 0.751	0.03 Percentage change Standard Deviation 0.681	-0.08 Percentage change Standard Deviation 0.837
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks Week 2	-0.45 Percentage change Standard Deviation 1.072	-0.49 Percentage change Standard Deviation 0.613	-0.08 Percentage change Standard Deviation 0.656	-0.14 Percentage change Standard Deviation 0.737
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks Week 3	-0.34 Percentage change Standard Deviation 1.114	-0.27 Percentage change Standard Deviation 0.757	-0.06 Percentage change Standard Deviation 0.634	-0.35 Percentage change Standard Deviation 0.782
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks Week 4	-0.36 Percentage change Standard Deviation 1.030	-0.26 Percentage change Standard Deviation 0.533	-0.03 Percentage change Standard Deviation 0.703	-0.29 Percentage change Standard Deviation 0.686

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: ITT population. Only those participants available at the time of assessment were analyzed.

Participants were analyzed whether they had any increase or decrease from the Baseline Hgb. Hgb increase based stopping criteria included analysis of Increase or decrease of more than or equal to (>=) 2 g/dL from the Baseline (pre-dose on Day 1) was recorded and also the participants with hemoglobin >=13 g/dL were recorded.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Participants Reaching Hgb Stopping Criteria >=2g/dL Hgb increase post Baseline	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants Reaching Hgb Stopping Criteria Post Baseline Hgb >=13.0	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Reaching Hgb Stopping Criteria Post Baseline Hgb <8.0	1 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: Safety population.

An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Only on-treatment data has been presented.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	9 Participants	7 Participants	1 Participants	6 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	0 Participants	2 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: Safety population

Discontinuation of the study drug could be due to safety-related reasons AE. The AEs responsible included anemia, gastrointestinal hemorrhage, and nausea.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Participants Discontinuing the Study Treatment Due to AEs	1 Participants	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: Pharmacokinetic (PK) population included all the participants who received at least one dose of the study drug and from whom at least one sample was withdrawn for PK analysis. Only those participants available at the specified time points were analyzed.

Each of the plasma concentration-time plot contained one plot on the untransformed scale (i.e. a linear plot) and one plot on the log transformed scale (i.e. log-linear plot). Plasma concentrations were analyzed for the study drug (GSK1278863), and its metabolites namely GSK2391220 (M2), GSK2531403 (M3), GSK2487818A (M4), GSK2506102A (M5), GSK2531398 (M6), and GSK2531401A (M13). Pharmacokinetic analysis was done on Weeks (W) 2 and 4 at a fixed timely interval of 5 hours (h) on W2 and every hour on W4. Only the data for last visit for W2 and last visit of W4 has been presented.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M2, Week 2, 7-11h	0.4582 Nanograms per milliliter (ng/mL) Standard Deviation 0.28340	1.5468 Nanograms per milliliter (ng/mL) Standard Deviation 1.11679	4.3165 Nanograms per milliliter (ng/mL) Standard Deviation 3.03668	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M2, Week 4, 3h	0.6780 Nanograms per milliliter (ng/mL) Standard Deviation 0.42493	2.0382 Nanograms per milliliter (ng/mL) Standard Deviation 1.98534	7.4288 Nanograms per milliliter (ng/mL) Standard Deviation 3.64287	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M3, Week 2, 7-11h	0.6386 Nanograms per milliliter (ng/mL) Standard Deviation 0.35940	2.1188 Nanograms per milliliter (ng/mL) Standard Deviation 1.60771	5.6935 Nanograms per milliliter (ng/mL) Standard Deviation 3.24262	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M4, Week 4, 3h	0.6016 Nanograms per milliliter (ng/mL) Standard Deviation 0.45551	1.8355 Nanograms per milliliter (ng/mL) Standard Deviation 1.89643	6.1856 Nanograms per milliliter (ng/mL) Standard Deviation 3.24320	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M5, Week 2, 7-11h	0.1546 Nanograms per milliliter (ng/mL) Standard Deviation 0.11679	0.5511 Nanograms per milliliter (ng/mL) Standard Deviation 0.41077	1.4581 Nanograms per milliliter (ng/mL) Standard Deviation 0.71612	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M6, Week 2, 7-11h	0.1776 Nanograms per milliliter (ng/mL) Standard Deviation 0.12140	0.6956 Nanograms per milliliter (ng/mL) Standard Deviation 0.47561	1.8957 Nanograms per milliliter (ng/mL) Standard Deviation 1.47442	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M13, Week 4, 3h	0.4651 Nanograms per milliliter (ng/mL) Standard Deviation 0.35442	1.3623 Nanograms per milliliter (ng/mL) Standard Deviation 1.40324	5.3494 Nanograms per milliliter (ng/mL) Standard Deviation 2.60236	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks GSK1278863, Week 2, 7-11h	0.2292 Nanograms per milliliter (ng/mL) Standard Deviation 0.40031	3.3148 Nanograms per milliliter (ng/mL) Standard Deviation 5.89540	5.6170 Nanograms per milliliter (ng/mL) Standard Deviation 15.91725	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks GSK1278863, Week 4, 3h	3.3113 Nanograms per milliliter (ng/mL) Standard Deviation 3.14336	17.9009 Nanograms per milliliter (ng/mL) Standard Deviation 12.89917	34.7253 Nanograms per milliliter (ng/mL) Standard Deviation 38.79049	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M3, Week 4, 3h	0.7921 Nanograms per milliliter (ng/mL) Standard Deviation 0.42785	2.2857 Nanograms per milliliter (ng/mL) Standard Deviation 2.03968	8.4582 Nanograms per milliliter (ng/mL) Standard Deviation 3.55548	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M4, Week 2, 7-11h	0.2156 Nanograms per milliliter (ng/mL) Standard Deviation 0.19430	0.8121 Nanograms per milliliter (ng/mL) Standard Deviation 0.69622	2.3216 Nanograms per milliliter (ng/mL) Standard Deviation 2.75137	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M5, Week 4, 3h	0.1995 Nanograms per milliliter (ng/mL) Standard Deviation 0.22453	0.7132 Nanograms per milliliter (ng/mL) Standard Deviation 1.08288	1.9972 Nanograms per milliliter (ng/mL) Standard Deviation 0.71061	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M6, Week 4, 3h	0.3235 Nanograms per milliliter (ng/mL) Standard Deviation 0.27845	1.0626 Nanograms per milliliter (ng/mL) Standard Deviation 1.35895	3.4569 Nanograms per milliliter (ng/mL) Standard Deviation 1.56093	—
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks M13, Week 2, 7-11h	0.4875 Nanograms per milliliter (ng/mL) Standard Deviation 0.38599	1.4014 Nanograms per milliliter (ng/mL) Standard Deviation 1.19096	3.9647 Nanograms per milliliter (ng/mL) Standard Deviation 1.86947	—

SECONDARY outcome

Timeframe: Up to 6 weeks (including follow-up)

Population: Safety population included all participants who received at least one dose of study drug.

Participants were analyzed up to 6 weeks for hematological and clinical chemistry parameters of PCI whether they had any higher or lower values than the reference range post screening. Normal alkaline phosphatase (ALP) was 0-46 U/L, aspartate amino transferase (AST) 0-42 U/L, ALP 20-125 U/L, total bilirubin 0-1.3 mg/dL, troponin 0-0.1ng/mL, Hgb 12 - 16 g/dL, platelets 140-450 G/L, creatine phosphokinase 29-168 U/L, creatinine 0.57 - 1.25 mg/dL, Potassium 3.6-5.0 mmol/L, hematocrit 38-45%; however, no participants with abnormal hematology and clinical chemistry parameters were recorded.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 6 weeks

Population: Safety population. Only the participants available at the time of assessment were analyzed.

Vital signs include systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Three measurements of SBP, DBP and HR were recorded from the participant in a supine position for at least 5 minutes (allowing enough time between measurement to completely deflate and loosen the inflatable cuff). Data has been presented for vital signs with values high and low from the reference range.

Outcome measures

Measure	0.5 mg GSK1278863 n=21 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Participants With Abnormal Vital Signs of PCI DBP, high	2 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Vital Signs of PCI SBP, low	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Vital Signs of PCI SBP, high	10 Participants	9 Participants	6 Participants	10 Participants
Number of Participants With Abnormal Vital Signs of PCI HR, low	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Vital Signs of PCI DBP, low	1 Participants	2 Participants	2 Participants	3 Participants
Number of Participants With Abnormal Vital Signs of PCI HR, high	0 Participants	0 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 6 weeks

Population: Safety population. Only the participants available at the time of assessment were analyzed.

Participants were analyzed for any abnormality in ECG and was categorized as abnormal clinically significant and abnormal and clinically insignificant. The parameters that were analyzed for ECG were atrial fibrillation, Atrial premature complex, Bigeminy, First degree AV block (PR interval > 200 msec), Incomplete right bundle branch block, Junctional rhythm, Junctional tachycardia (heart rate >100 beats/min), Left anterior hemi block (synonymous to left anterior fascicular block), Left atrial abnormality, Left axis deviation (QRS axis more negative than -30 degrees), Left bundle branch block, Left ventricular hypertrophy, Myocardial infarction, anterior, Myocardial infarction, inferior, Non-specific ST-T changes, Normal sinus rhythm, Poor R wave progression, Right atrial abnormality, Right QRS axis deviation, bundle block, ventricular hypertrophy, ST depression or abnormality, AV block, arrhythmia, short PR interval, bradycardia, tachycardia, and T-wave abnormality.

Outcome measures

Measure	0.5 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 0.5 mg once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=20 Participants Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=19 Participants Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=19 Participants Eligible participants received oral rhEPO or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Number of Participants With Electrocardiogram (ECG) Findings Over Period Abnormal, clinically significant	10 Participants	12 Participants	8 Participants	12 Participants
Number of Participants With Electrocardiogram (ECG) Findings Over Period Abnormal, not clinically significant	5 Participants	6 Participants	9 Participants	6 Participants

Adverse Events

0.5 mg GSK1278863

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

2 mg GSK1278863

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

5 mg GSK1278863

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

rhEPO

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	0.5 mg GSK1278863 n=21 participants at risk Eligible participants received oral GK1278863 0.5 milligrams (mg) once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=21 participants at risk Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=20 participants at risk Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 participants at risk Eligible participants received oral recombinant human erythropoietin (rhEPO ) or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Gastrointestinal disorders Constipation	0.00% 0/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	4.8% 1/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.
Gastrointestinal disorders Gastrointestinal hemorrhage	0.00% 0/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	4.8% 1/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	5.0% 1/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	5.0% 1/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.

Other adverse events

Measure	0.5 mg GSK1278863 n=21 participants at risk Eligible participants received oral GK1278863 0.5 milligrams (mg) once daily for 4 weeks and we re followed-up for 2 weeks	2 mg GSK1278863 n=21 participants at risk Eligible participants received oral GK1278863 2.0 mg once daily for 4 weeks and were followed-up for 2 weeks	5 mg GSK1278863 n=20 participants at risk Eligible participants received oral GK1278863 5.0 mg once daily for 4 weeks and were followed-up for 2 weeks.	rhEPO n=20 participants at risk Eligible participants received oral recombinant human erythropoietin (rhEPO ) or darbepoetin once daily for 4 weeks and were followed-up for 2 weeks
Blood and lymphatic system disorders Anemia	14.3% 3/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	4.8% 1/21 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.	0.00% 0/20 • Up to 4 weeks Safety population was used to collect AEs and SAEs.

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