Baseline was defined as the value on Day 1. CFB was calculated by subtracting the baseline value from the post-dose value at Week 4. To model the dose-response relationship a four-parameter Emax model was used. E0 is the expected Hgb change from Baseline for a participant receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a participant receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Minimal Effective Dose (MED) is defined as the smallest dose that achieves a placebo-corrected change of 0.5 g/dL over Week 4. Target dose (TD) is defined as the dose that achieves a placebo-corrected 1.0 g/dL change over Week 4. Maximum Acceptable Dose (MAD) is defined as the dose that achieves a placebo-corrected 2.0 g/dL change over Week 4.

Intent-to-Treat (ITT) population comprised 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 those participants with data available at the indicated time points were analyzed.

Hgb assessments were performed at Baseline, Week 1, Week 2, Week 3, W eek4/Early withdrawal and Week 8 (follow-up) based on central laboratory (Quest diagnosis). Baseline was defined as the value on Day 1. CFB was calculated by subtracting the Baseline value from the post-dose value at Week 4.

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

Hgb response was defined as achieving an increase of at least 0.5 g/dL, 1.0 g/dL, 1.5 g/dL, and 2.0 g/dL in Hgb. The number of participants with Hgb response: Hgb increase <-1.0, Hgb increase -1.0 -< -0.5, Hgb increase -0.5 -< 0.5, Hgb increase 0.5 -< 1.0 and Hgb increase >=1.0 have been presented.

ITT population. Only those participants available at the indicated time points were analyzed.

Hgb response was defined as achieving an increase of at least 0.5 g/dL, 1.0 g/dL, 1.5 g/dL, and 2.0 g/dL in Hgb. The percentage of participants with Hgb response: Hgb increase <-1.0, Hgb increase -1.0 -< -0.5, Hgb increase -0.5 -< 0.5, Hgb increase 0.5 -< 1.0 and Hgb increase >=1.0 have been presented.

ITT population. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm.

Hgb stopping criteria was defined as: (1) Hgb <7.5 g/dL (2) 7.5 <= Hgb <1 3.0 g/dL and >2 g/dL Hgb change over 2W (3) Hgb >=13.0 g/dL. The number of participants who reached pre-defined Hgb stopping criteria have been presented.

ITT population.

Blood samples for EPO were collected on Day 1 (pre-dose), Week 2 (collected approx 6-12 hours post-dose on arrival and after 1, 2 and 3 hours) and Week 4 (pre-dose and 3 hours post-dose). Maximum observed value meant maximum value between Week 1 and Week 4. Baseline was defined as the value on Day 1. Maximum observed CFB was calculated by subtracting the Baseline value from the maximum observed value between Week 1 and Week 4.

ITT population. Only those participants with data available at the indicated time points were analyzed.

Blood samples for VEGF were collected on Day 1 (pre-dose), Week 2 (collected approximately 6-12 hours post-dose on arrival and after 1, 2 and 3 hours) and Week 4 (pre-dose and 3 hours post-dose). Maximum observed value meant maximum value between Week 1 and Week 4. Baseline was defined as the value on Day 1. Maximum observed percent CFB was calculated as 100 multiplied by the maximum observed exponential mean change on a log scale minus 1.

ITT population. Only those participants with data available at the indicated time points were analyzed.

Blood samples for hepcidine were collected on Day 1 (pre-dose), Week 2 (collected approximately 6-12 hours post-dose) and Week 4 (pre-dose). Baseline was defined as the value on Day 1. Percent CFB was calculated as 100 multiplied by the exponential mean change on a log scale minus 1.

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

Ferritin was used as marker of iron metabolism and utilization. Baseline was defined as the value on Day 1. CFB was calculated by subtracting the Baseline value from the post dose value at Week 4.

ITT population. Only those participants with data available at the specified time points were analyzed.

TIBC, UIBC and Iron were used as marker of iron metabolism and utilization. Baseline was defined as the value on Day 1. CFB was calculated by subtracting the Baseline value from the post-dose value at Week 4.

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

Transferrin was used as marker of iron metabolism and utilization. Baseline was defined as the value on Day 1. CFB was calculated by subtracting the Baseline value from the post-dose value at Week 4.

ITT population. Only those participants with data available at the indicated time points were analyzed.

TS was used as marker of iron metabolism and utilization. Baseline was defined as the value on Day 1. Percent CFB was calculated as 100 multiplied by the exponential mean change on a log scale minus 1.

ITT population. Only those participants with data available at the indicated time points were analyzed.

Blood samples for plasma pharmacokinetic analysis were collected at Week 4 (pre-dose, 1, 2, 3 hours post-dose). Individual plasma GSK1278863 and M-GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531401, GSK2531403 concentrations have been presented.

Pharmacokinetic Population: All participants from whom a Pharmacokinetic sample was obtained and analyzed. Only those participants available at the indicated time points were analyzed.

An AE is defined as any untoward medical occurrence in clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any AE which results in death; is life-threatening; requires participant hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event.

Safety population.

The PCI range was as follows: alkaline phosphates >= 3 times upper limit of normal range [ULRR]), potassium (>0.5 millimoles/liter below the LLRR or >1.0 millimoles/liter above the ULRR), phosphate (>0.323 millimoles/liter above ULRR or below lower limit reference range [LLRR]), glucose (<3.9 or >22 millimoles/liter), magnesium (<LLRR or > 0.3 milimoles/liter above ULRR), lymphocytes <0.5x LLRR, neutrophils (<0.5 times LLRR), platelets (80 or >500 times giga/liter), platelets (80 or >500 times giga/liter) and leukocytes >1 x giga/liter below the LLRR or >5 x GI/L above the ULRR. The participants who had PCI values higher and lower than the reference range have been presented.

Safety population. Only those participants available at the specified time points were analyzed.

Vital signs SBP and DBP were recorded pre-dialysis and post-dialysis. Measurements were taken from the participant while in a seated position or semi-supine in the dialysis chair. PCI range for SBP was < 85 or > 170 and for DBP was < 45 or > 100 millimeters of mercury. Participant's with values high and low from the PCI range have been presented.

Safety population. Only those participants available at the specified time points were analyzed.

Vital sign HR was recorded pre-dialysis and post-dialysis. Measurements were taken from the participant while in a seated position or semi-supine in the dialysis chair. PCI range for HR was < 40 or > 110 beats per minute. Participant's with values higher than the PCI range have been presented.

Safety population. Only those participants available at the specified time points were analyzed.

Full 12-lead ECGs included heart rate, PR, QRS, QT and QTc intervals. Measurements were taken from the participant while in a supine position. ECGs were performed consistently either before or after dialysis throughout the study. ECG abnormalities characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS) upto W4 have been presented.

Safety population.