A Study to Evaluate Safety and Efficacy of GSK1278863 in... | NCT01977573

Label	Type	Description	Intervention Names
GSK1278863	Experimental	Subjects will be administered GSK1278863 QD. Starting dose will be based on data from previous studies with GSK1278863 and dose-response modelling, as well as Baseline Hgb concentration. After 4 Week of fixed dose period, dose may be adjusted to achieve Hgb 9.0 to 10.5 g/dL	Drug: GSK1278863
Control	Other	All subjects who are randomized to the Control arm will receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, to maintain Hgb levels within the target range. The decision around whether a subject requires rhEPO, selection of the type of rhEPO and rhEPO dose should be based on Investigator clinical judgment, with the historical rhEPO dose (where applicable) and the current Hgb value being considered.	Drug: rhEPO

Name	Type	Description	Arm Group Labels	Other Names
GSK1278863	Drug	Film-coated tablets containing 0.5 mg, 1 mg, 2 mg, 5mg or matching placebo	GSK1278863

Measure	Description	Time Frame
Summary of Hemoglobin (Hgb) Concentration at Week 24	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.	Week 24

Measure	Description	Time Frame
Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	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.	Week 24
Number of Participants Reaching Pre-defined Hgb Stopping Criteria

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age: >=18 years of age. (Week -4 verification only)
Gender: Female and male subjects. (Week -4 verification only) Females: If of childbearing potential, must agree to use one of the approved contraception methods, from Screening until completion of the Follow-up Visit OR Of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy, or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved contraception methods if they wish to continue their HRT during the study. Otherwise they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Corrected QT interval (QTc): Bazett's Correction of QT Interval (QTcB) <470 milliseconds (msec) or QTcB <480 msec in subjects with bundle branch block. There is no QTc criterion for subjects with a predominantly paced rhythm.
CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3/4/5 defined by electronic estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
Hgb: Group 1 (rhEPO naïve): Baseline Hgb of 8.0-11.0 g/dL (inclusive) (USA sites only: 8.0-10.0 g/dL, inclusive); Group 2 (rhEPO users): Baseline Hgb of 9.0-11.5 g/dL (inclusive) (USA sites only: 9.0-10.5, inclusive).
Stable rhEPO dose for rhEPO users: Group 2 subjects must be using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses that varied by no more than 50% during the 4 weeks prior to Week -4. At Day 1 (randomization), confirm that total weekly doses varied by no more than 50% during the screening period.
Oral iron therapy: If on oral iron, then doses must not be changed for the 4 weeks prior to Week -4, during the screening phase, and through the first 4 weeks after Randomization.

Exclusion Criteria:

Dialysis: On dialysis or planning to initiate dialysis during the study.
Renal transplant: Pre-emptive or scheduled renal transplant.
High rhEPO dose: An epoetin dose of >=360 IU/kg/week intravenous (IV) or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram per kilogram per week (mcg/kg/week) IV or SC within the prior 8 weeks through Day 1 (randomization).
Use of methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Day 1 (randomization).
IV iron therapy: Use of IV iron for 4 weeks prior to Screening Week -4, during the screening phase, and through the first 4 weeks after Randomization
Vitamin B12: Below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
Folate: <2.0 nanogram per millilitre (ng/mL) (<4.5 nanomoles per liter [nmol/L]) (may rescreen in a minimum of 4 weeks).
Ferritin: <40 ng/mL (<40 mcg/L).
Transferrin saturation (TSAT): Below the lower limit of the reference range
Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization).
Stroke or transient ischemic attack: Within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
Heart failure: Class III/IV heart failure as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Week -4 Screening through Day 1 (randomization), symptomatic right heart failure diagnosed prior to Week -4 Screening through Day 1 (randomization).
Uncontrolled hypertension: Defined as diastolic blood pressure (DBP) >100 mmHg or systolic blood pressure (SBP) >170 mmHg at Week -4 and reconfirmed at Day 1.
Thrombotic Disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), except vascular access thrombosis within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
Ophthalmology disease: Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam.
Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Week -4 Screening through Day 1 (randomization).
Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1 (randomization).
Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 x upper limit of normal (ULN) or total bilirubin >1.5 x ULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
Major surgery: Major surgery (excluding vascular access surgery) within the prior 8 weeks, during the Week -4 Screening phase or planned during the study.
Transfusion: Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study.
Gastrointestinal (GI) Bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
Acute infection: Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
Malignancy: Subjects with a history of malignancy within the prior 5 years, who receiving treatment for cancer, or who have a strong family history of cancer (e.g., familial cancer disorders); with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated prior to Week -4 Screening through Day 1 (randomization).
Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product (see GSK1278863 IB for list of excipients and rhEPO (refer to local product labelling for details).
Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Week -4 Screening until the Follow-up Visit.
Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Week -4 Screening through Day 1 (randomization).
Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the Investigator considers would put the subject at unacceptable risk.
Patient participation: Unwillingness or inability of the subject to follow the procedures or lifestyle or dietary restrictions outlined in the protocol.
Pregnancy or Lactation: Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or during the trial.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Peoria	Arizona	85381	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
36005278	Derived	Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

ID	Title	Description
FG000	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.
FG001

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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).
BG003	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.
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Summary of Hemoglobin (Hgb) Concentration at Week 24

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.

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.

Posted

Mean

Standard Deviation

grams per deciliter

Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).
OG003	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.

Units	Counts
Participants	OG000123 OG00143 OG00233 OG003

Title

Denominators

Categories

Original n=45,15,19,13

Title	Measurements
	OG00010.20± 0.906 OG00110.64± 0.664 OG00210.03± 0.522 OG003

Secondary

Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24

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.

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

Posted

Number

participants

Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Number of Participants Reaching Pre-defined Hgb Stopping Criteria

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.

ITT population.

Posted

Number

Participants

Over a period of 24 Weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	rhEPO-User GSK1278863

Secondary

Percent Change From Baseline in Hepcidin Concentration at Week 24

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.

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.

Posted

Geometric Mean

95% Confidence Interval

percent change in Hepcidin

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)

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.

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

Posted

Mean

Standard Deviation

International Units per liter

Baseline to Week 24

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)

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.

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

Posted

Geometric Mean

95% Confidence Interval

percent change in VEGF concentration

Baseline and up to Week 24

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24

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.

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

Posted

Mean

Standard Deviation

percentage of days

Weeks 12 to 24

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Change From Baseline in Ferritin Concentration at Week 24

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

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

Posted

Mean

Standard Deviation

micrograms per liter

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Change From Baseline in Transferrin Concentration at Week 24

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.

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

Posted

Mean

Standard Deviation

grams per liter

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Percent Change From Baseline in Transferrin Saturation at Week 24

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.

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

Posted

Geometric Mean

95% Confidence Interval

percent change

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Change From Baseline in Total Iron at Week 24

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

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

Posted

Mean

Standard Deviation

micromoles per liter

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24

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.

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

Posted

Mean

Standard Deviation

micromoles per liter

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	rhEPO-User GSK1278863

Secondary

Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24

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.

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

Posted

Mean

Standard Deviation

picogram

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	rhEPO-User GSK1278863

Secondary

Change From Baseline in Hematocrit at Week 24

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

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

Posted

Mean

Standard Deviation

percentage change in Fraction of 1

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Change From Baseline in Red Blood Cell Count at Week 24

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.

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

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Change From Baseline in Reticulocyte Cell Count at Week 24

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.

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

Posted

Mean

Standard Deviation

percentage of reticulocytes

Baseline and Week 24

ID	Title	Description
OG000	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.
OG001	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.
OG002

Secondary

Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint

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.

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

Posted

Mean

Standard Deviation

nanograms per milliliter

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)

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Mean Number of Dose Adjustments up to 24 Weeks

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.

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

Posted

Mean

Standard Deviation

number of adjustments

From Week 4 up to 24 Weeks

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency

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

Posted

Number

participants

From week 4 up to 24 weeks

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20

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

Posted

Number

Participants

From Week 4 up to Week 20

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks

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.

ITT population.

Posted

Mean

Standard Deviation

milligrams

Up to 24 Weeks

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Mean Final Dose of GSK1278863 up to 24 Weeks

ITT population.

Posted

Mean

Standard Deviation

milligrams per day

Up to 24 Weeks

ID	Title	Description
OG000	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.
OG001	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).

Secondary

Number of Hemoglobin (Hgb) Excursions

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.

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

Posted

Number

number of excursions

Up to 24 Weeks.

ID	Title	Description
OG000	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.
OG001	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.
OG002	rhEPO-User GSK1278863

Secondary

Number of Hemoglobin (Hgb) Cycles up to 24 Weeks

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.

Completers population. Only participants with Hgb cycles were analyzed.

Posted

Number

number of Hgb cycles

Up to 24 Weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Number of Dose Cycles up to 24 Weeks

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

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

Posted

Number

number

Up to 24 weeks

ID	Title	Description
OG000	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.
OG001	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).

Units	Counts
Participants

Secondary

Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.

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

Completers population.

Posted

Number

participants

Up to 24 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks

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.

Completers population.

Posted

Number

participants

Up to 24 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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).

Secondary

Number of Participants With at Least One Dose Cycle up to 24 Weeks

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

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

Posted

Number

participants

Up to 24 weeks

ID	Title	Description
OG000	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.
OG001	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).

Units	Counts

Secondary

Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline

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.)

ITT Population

Posted

Number

participants

From Day 1 up to Week 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	rhEPO-User GSK1278863

Secondary

Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit

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.

ITT population.

Posted

Number

participants

From Week 4 up to Week 24

ID	Title	Description
OG000	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.
OG001	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).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	23	134	47	134
EG001	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.	7	45	14	45
EG002	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).	7	36	20	36
EG003	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.	7	35	13	35

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANY EVENT	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0013 affected45 at risk EG0022 affected36 at risk EG0033 affected35 at risk
RENAL FAILURE CHRONIC	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0012 affected45 at risk EG0021 affected36 at risk EG003
GLOMERULONEPHRITIS CHRONIC	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
DIABETIC NEPHROPATHY	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
RENAL FAILURE	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
RENAL IMPAIRMENT	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0013 affected45 at risk EG0021 affected36 at risk EG003
PNEUMONIA	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0011 affected45 at risk EG0021 affected36 at risk EG003
PYELONEPHRITIS CHRONIC	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
APPENDICITIS	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
CELLULITIS	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
PNEUMONIA PNEUMOCOCCAL	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0004 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
ANGINA PECTORIS	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ATRIOVENTRICULAR BLOCK COMPLETE	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CARDIAC FAILURE CONGESTIVE	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
MYOCARDIAL ISCHAEMIA	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CARDIAC FAILURE	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
GASTRIC ULCER	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
SMALL INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
RECTAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
FLUID OVERLOAD	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
HYPOGLYCAEMIA	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
CARPAL TUNNEL SYNDROME	Nervous system disorders	MedDRA 16.1s	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CEREBRAL MICROANGIOPATHY	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
NEURALGIA	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
DIABETIC VASCULAR DISORDER	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
HYPERTENSION	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ORTHOSTATIC HYPOTENSION	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Investigations	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
FALSE POSITIVE INVESTIGATION RESULT	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CHONDROCALCINOSIS PYROPHOSPHATE	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CONFUSIONAL STATE	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
MENTAL STATUS CHANGES	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CHEST PAIN	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
HEPATIC CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
ANY EVENT	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Fatigue	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Biliary sepsis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
Bronchitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Sepsis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Shunt malfunction	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Gallbladder adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
Metabolic encephalopathy	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
Hypotension	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
NASOPHARYNGITIS	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG00015 affected134 at risk EG0012 affected45 at risk EG0027 affected36 at risk EG0032 affected35 at risk
CONJUNCTIVITIS	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0022 affected36 at risk EG003
BRONCHITIS	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0011 affected45 at risk EG0020 affected36 at risk EG003
DIARRHOEA	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG00010 affected134 at risk EG0010 affected45 at risk EG0020 affected36 at risk EG003
NAUSEA	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0008 affected134 at risk EG0011 affected45 at risk EG0021 affected36 at risk EG003
CONSTIPATION	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0005 affected134 at risk EG0011 affected45 at risk EG0021 affected36 at risk EG003
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0012 affected45 at risk EG0021 affected36 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0011 affected45 at risk EG0021 affected36 at risk EG003
OEDEMA PERIPHERAL	General disorders	MedDRA 16.1	Systematic Assessment	EG0005 affected134 at risk EG0010 affected45 at risk EG0022 affected36 at risk EG003
FATIGUE	General disorders	MedDRA 16.1	Systematic Assessment	EG0003 affected134 at risk EG0011 affected45 at risk EG0021 affected36 at risk EG003
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0010 affected45 at risk EG0022 affected36 at risk EG003
GOUT	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected134 at risk EG0014 affected45 at risk EG0020 affected36 at risk EG003
HYPERTENSION	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected134 at risk EG0011 affected45 at risk EG0024 affected36 at risk EG003
BLOOD PRESSURE INCREASED	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0003 affected134 at risk EG0010 affected45 at risk EG0021 affected36 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected134 at risk EG0011 affected45 at risk EG0023 affected36 at risk EG003
Asthenia	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0013 affected45 at risk EG0021 affected36 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected134 at risk EG0010 affected45 at risk EG0022 affected36 at risk EG003

ID	Term
D000740	Anemia
D051436	Renal Insufficiency, Chronic

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms