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

A 24-week, Phase IIB, Randomized, Controlled, Parallel Group, Multi-center Study to Evaluate the Safety and Efficacy of GSK1278863 in Subjects With Anemia Associated With Chronic Kidney Diseases Who Are Not on Dialysis.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01977573

Enrollment

252

Registered

2013-11-06

Start date

2013-10-31

Completion date

2015-06-15

Last updated

2018-10-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anaemia

Keywords

Prolyl hydroxylase inhibitor, pharmacokinetics, GSK1278863, Anemia, hemoglobin, erythropoiesis stimulating agents, Chronic kidney disease

Brief summary

This study will be conducted in approximately 228 subjects with anemia associated with CKD who are not on dialysis. Two groups of subjects will be enrolled into the study: Group 1: recombinant human erythropoietin (rhEPO) naive subjects; Group 2: rhEPO users, who are currently receiving rhEPO. Subjects who are rhEPO naive will be randomized to receive either GSK1278863 once daily (QD) or rhEPO in a 3:1 fashion; subjects who are receiving an rhEPO before enrolling (rhEPO users) will be randomized in a 1:1 fashion to GSK1278863 QD or to the control arm. For those randomized to the control arm, the decision around whether the subject requires rhEPO, the selection of the type of rhEPO (if needed) and the choice of rhEPO dose to achieve and maintain Hgb concentrations within the target range should be based on Investigator clinical judgment, with the historical rhEPO dose and the current Hgb value being considered. The study consists of a screening phase of at least 4 weeks, a 24-week treatment phase and a follow-up visit that will occur approximately 4 weeks after completing treatment. It is anticipated that the data generated will enable selection of the starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials.

Interventions

DRUGGSK1278863

Film-coated tablets containing 0.5 mg, 1 mg, 2 mg, 5mg or matching placebo

DRUGrhEPO

Locally sourced rhEPO. 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..

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change From Baseline in Hematocrit at Week 24	Baseline and 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.
Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	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.
Number of Participants Reaching Pre-defined Hgb Stopping Criteria	Over a period of 24 Weeks	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.
Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)	Baseline to Week 24	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.
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)	Baseline and up to Week 24	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.
Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Weeks 12 to 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.
Change From Baseline in Red Blood Cell Count at Week 24	Baseline and 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.
Change From Baseline in Ferritin Concentration at Week 24	Baseline and Week 24	Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value.
Change From Baseline in Transferrin Concentration at Week 24	Baseline and 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.
Percent Change From Baseline in Transferrin Saturation at Week 24	Baseline and 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.
Change From Baseline in Total Iron at Week 24	Baseline and 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.
Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24	Baseline and 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.
Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24	Baseline and 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.
Change From Baseline in Reticulocyte Cell Count at Week 24	Baseline and 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.
Percent Change From Baseline in Hepcidin Concentration at Week 24	Baseline and 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.
Mean Number of Dose Adjustments up to 24 Weeks	From Week 4 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.
Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	From week 4 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. Frequency is presented as the number of participants with dose adjustment(s) once, twice, thrice, four times, or five times.
Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	From Week 4 up to Week 20	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. The number of participants with an adjustment are presented at the timings at which adjustments were done.
Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks	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.
Mean Final Dose of GSK1278863 up to 24 Weeks	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.
Number of Hemoglobin (Hgb) Excursions	Up to 24 Weeks.	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.
Number of Hemoglobin (Hgb) Cycles up to 24 Weeks	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.
Number of Dose Cycles up to 24 Weeks	Up to 24 weeks	A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease).
Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.	Up to 24 weeks	A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter.
Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks	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.
Number of Participants With at Least One Dose Cycle up to 24 Weeks	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
Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	From Day 1 up to Week 28	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.)
Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	From Week 4 up to Week 24	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.
Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	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)	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.

Countries

Australia, Canada, Czechia, Denmark, France, Germany, Hungary, Japan, Poland, Russia, South Korea, Spain, Sweden, United Kingdom, United States

Participant flow

Recruitment details

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

Pre-assignment details

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

Participants by arm

Arm	Count
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.	123
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.	43
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).	33
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.	36
Total	235

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	7	0	2	1
Overall Study	Lost to Follow-up	1	0	0	1
Overall Study	Physician Decision	1	0	0	0
Overall Study	Protocol Violation	3	1	0	0
Overall Study	Reached Defined Stopping Criteria	2	1	1	0
Overall Study	Withdrawal by Subject	6	1	1	1

Baseline characteristics

Characteristic	rhEPO-Naive GSK1278863	rhEPO-Naive Control	rhEPO-User GSK1278863	rhEPO-User Control	Total
Age, Continuous	67.6 Years STANDARD_DEVIATION 12.21	64.3 Years STANDARD_DEVIATION 14.22	62.0 Years STANDARD_DEVIATION 14.06	66.7 Years STANDARD_DEVIATION 12.89	66.1 Years STANDARD_DEVIATION 13.04
Race/Ethnicity, Customized African American/African Heritage	14 Participants	2 Participants	2 Participants	4 Participants	22 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Japanese/East Asian/South East Asian Heritage	28 Participants	11 Participants	9 Participants	12 Participants	60 Participants
Race/Ethnicity, Customized White	81 Participants	30 Participants	22 Participants	19 Participants	152 Participants
Sex: Female, Male Female	75 Participants	23 Participants	17 Participants	23 Participants	138 Participants
Sex: Female, Male Male	48 Participants	20 Participants	16 Participants	13 Participants	97 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	47 / 134	14 / 45	20 / 36	13 / 35
serious Total, serious adverse events	23 / 134	7 / 45	7 / 36	7 / 35

Outcome results

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.

Time frame: Week 24

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

Arm	Measure	Group	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Summary of Hemoglobin (Hgb) Concentration at Week 24	Original n=45,15,19,13	10.20 grams per deciliter	Standard Deviation 0.906
rhEPO-Naive GSK1278863	Summary of Hemoglobin (Hgb) Concentration at Week 24	Amended n=61,21,11,17	10.96 grams per deciliter	Standard Deviation 1.044
rhEPO-Naive Control	Summary of Hemoglobin (Hgb) Concentration at Week 24	Amended n=61,21,11,17	11.05 grams per deciliter	Standard Deviation 1.144
rhEPO-Naive Control	Summary of Hemoglobin (Hgb) Concentration at Week 24	Original n=45,15,19,13	10.64 grams per deciliter	Standard Deviation 0.664
rhEPO-User GSK1278863	Summary of Hemoglobin (Hgb) Concentration at Week 24	Original n=45,15,19,13	10.03 grams per deciliter	Standard Deviation 0.522
rhEPO-User GSK1278863	Summary of Hemoglobin (Hgb) Concentration at Week 24	Amended n=61,21,11,17	10.42 grams per deciliter	Standard Deviation 0.827
rhEPO-User Control	Summary of Hemoglobin (Hgb) Concentration at Week 24	Original n=45,15,19,13	10.66 grams per deciliter	Standard Deviation 0.62
rhEPO-User Control	Summary of Hemoglobin (Hgb) Concentration at Week 24	Amended n=61,21,11,17	10.86 grams per deciliter	Standard Deviation 1.182

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Ferritin Concentration at Week 24	-30.8 micrograms per liter	Standard Deviation 110.5
rhEPO-Naive Control	Change From Baseline in Ferritin Concentration at Week 24	-2.4 micrograms per liter	Standard Deviation 77.06
rhEPO-User GSK1278863	Change From Baseline in Ferritin Concentration at Week 24	-63.4 micrograms per liter	Standard Deviation 141.93
rhEPO-User Control	Change From Baseline in Ferritin Concentration at Week 24	-20.4 micrograms per liter	Standard Deviation 63.38

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Hematocrit at Week 24	2.64 percentage change in Fraction of 1	Standard Deviation 3.389
rhEPO-Naive Control	Change From Baseline in Hematocrit at Week 24	3.13 percentage change in Fraction of 1	Standard Deviation 3.245
rhEPO-User GSK1278863	Change From Baseline in Hematocrit at Week 24	-0.66 percentage change in Fraction of 1	Standard Deviation 3.074
rhEPO-User Control	Change From Baseline in Hematocrit at Week 24	2.09 percentage change in Fraction of 1	Standard Deviation 3.243

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Red Blood Cell Count at Week 24	0.28 10^12 cells per liter	Standard Deviation 0.377
rhEPO-Naive Control	Change From Baseline in Red Blood Cell Count at Week 24	0.34 10^12 cells per liter	Standard Deviation 0.365
rhEPO-User GSK1278863	Change From Baseline in Red Blood Cell Count at Week 24	-0.08 10^12 cells per liter	Standard Deviation 0.312
rhEPO-User Control	Change From Baseline in Red Blood Cell Count at Week 24	0.22 10^12 cells per liter	Standard Deviation 0.318

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Reticulocyte Cell Count at Week 24	-0.02 percentage of reticulocytes	Standard Deviation 0.551
rhEPO-Naive Control	Change From Baseline in Reticulocyte Cell Count at Week 24	-0.12 percentage of reticulocytes	Standard Deviation 0.648
rhEPO-User GSK1278863	Change From Baseline in Reticulocyte Cell Count at Week 24	0.27 percentage of reticulocytes	Standard Deviation 0.892
rhEPO-User Control	Change From Baseline in Reticulocyte Cell Count at Week 24	-0.09 percentage of reticulocytes	Standard Deviation 0.755

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24	-0.19 picogram	Standard Deviation 1.109
rhEPO-Naive Control	Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24	-0.33 picogram	Standard Deviation 1.085
rhEPO-User GSK1278863	Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24	-0.32 picogram	Standard Deviation 0.864
rhEPO-User Control	Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24	-0.19 picogram	Standard Deviation 1.546

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Total Iron at Week 24	1.0 micromoles per liter	Standard Deviation 5.01
rhEPO-Naive Control	Change From Baseline in Total Iron at Week 24	2.5 micromoles per liter	Standard Deviation 5.98
rhEPO-User GSK1278863	Change From Baseline in Total Iron at Week 24	-1.8 micromoles per liter	Standard Deviation 5.54
rhEPO-User Control	Change From Baseline in Total Iron at Week 24	0.7 micromoles per liter	Standard Deviation 8.36

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24	3.2 micromoles per liter	Standard Deviation 6.46
rhEPO-Naive Control	Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24	0.1 micromoles per liter	Standard Deviation 5.17
rhEPO-User GSK1278863	Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24	3.0 micromoles per liter	Standard Deviation 9.44
rhEPO-User Control	Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24	-1.0 micromoles per liter	Standard Deviation 6.69

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Change From Baseline in Transferrin Concentration at Week 24	0.077 grams per liter	Standard Deviation 0.3577
rhEPO-Naive Control	Change From Baseline in Transferrin Concentration at Week 24	-0.008 grams per liter	Standard Deviation 0.2694
rhEPO-User GSK1278863	Change From Baseline in Transferrin Concentration at Week 24	0.171 grams per liter	Standard Deviation 0.4124
rhEPO-User Control	Change From Baseline in Transferrin Concentration at Week 24	0.018 grams per liter	Standard Deviation 0.2395

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 6-12 hour Post-Dose, n=116, 31	2.0 nanograms per milliliter	Standard Deviation 5.18
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 7-13 hour Post-Dose, n=117, 31	2.3 nanograms per milliliter	Standard Deviation 7.06
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.6 nanograms per milliliter	Standard Deviation 4.93
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.4 nanograms per milliliter	Standard Deviation 4.52
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, Pre-Dose, n=111, 29	0.6 nanograms per milliliter	Standard Deviation 3.07
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, 1 hour Post-Dose, n=110, 28	22.8 nanograms per milliliter	Standard Deviation 35.93
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, 2 hour Post-Dose, n=109, 29	17.0 nanograms per milliliter	Standard Deviation 28.57
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, 3 hour Post-Dose, n=109, 29	11.6 nanograms per milliliter	Standard Deviation 19.56
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.2 nanograms per milliliter	Standard Deviation 5.21
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.1 nanograms per milliliter	Standard Deviation 5.67
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.8 nanograms per milliliter	Standard Deviation 5.01
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 9-15 hour Post-Dose, n=116, 31	2.6 nanograms per milliliter	Standard Deviation 4.89
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, Pre-Dose, n=111, 29	1.0 nanograms per milliliter	Standard Deviation 2.06
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, 1 hour Post-Dose, n=110, 28	2.1 nanograms per milliliter	Standard Deviation 3.52
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, 2 hour Post-Dose, n=109, 29	3.8 nanograms per milliliter	Standard Deviation 5.08
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, 3 hour Post-Dose, n=109, 29	4.5 nanograms per milliliter	Standard Deviation 5.43
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.2 nanograms per milliliter	Standard Deviation 3.87
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 7-13 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter	Standard Deviation 4.11
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter	Standard Deviation 4.48
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.9 nanograms per milliliter	Standard Deviation 4.09
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, Pre-Dose, n=111, 29	0.2 nanograms per milliliter	Standard Deviation 0.56
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, 1 hour Post-Dose, n=110, 28	1.4 nanograms per milliliter	Standard Deviation 3.07
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, 2 hour Post-Dose, n=109, 29	2.8 nanograms per milliliter	Standard Deviation 4.28
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, 3 hour Post-Dose, n=109, 29	3.1 nanograms per milliliter	Standard Deviation 4.07
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter	Standard Deviation 1.3
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.0 nanograms per milliliter	Standard Deviation 1.51
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 8-14 hour Post-Dose, n=116, 31	0.9 nanograms per milliliter	Standard Deviation 1.19
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.9 nanograms per milliliter	Standard Deviation 1.29
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, Pre-Dose, n=111, 29	0.4 nanograms per milliliter	Standard Deviation 0.73
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, 1 hour Post-Dose, n=110, 28	0.6 nanograms per milliliter	Standard Deviation 0.88
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, 2 hour Post-Dose, n=109, 29	0.9 nanograms per milliliter	Standard Deviation 1.15
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, 3 hour Post-Dose, n=109, 29	1.1 nanograms per milliliter	Standard Deviation 1.25
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0.01
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.3 nanograms per milliliter	Standard Deviation 2.06
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.2 nanograms per milliliter	Standard Deviation 2.5
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter	Standard Deviation 2.01
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter	Standard Deviation 2.1
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, Pre-Dose, n=111, 29	0.3 nanograms per milliliter	Standard Deviation 0.87
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, 1 hour Post-Dose, n=110, 28	0.8 nanograms per milliliter	Standard Deviation 1.53
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, 2 hour Post-Dose, n=109, 29	1.6 nanograms per milliliter	Standard Deviation 2.31
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, 3 hour Post-Dose, n=109, 29	2.0 nanograms per milliliter	Standard Deviation 2.42
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 6-12 hour Post-Dose, n=116, 31	2.8 nanograms per milliliter	Standard Deviation 4
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 7-13 hour Post-Dose, n=117, 31	2.7 nanograms per milliliter	Standard Deviation 3.58
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.7 nanograms per milliliter	Standard Deviation 3.74
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 9-15 hour Post-Dose, n=116, 31	2.5 nanograms per milliliter	Standard Deviation 3.53
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, Pre-Dose, n=111, 29	1.3 nanograms per milliliter	Standard Deviation 2.41
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, 1 hour Post-Dose, n=110, 28	1.6 nanograms per milliliter	Standard Deviation 2.65
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, 2 hour Post-Dose, n=109, 29	2.3 nanograms per milliliter	Standard Deviation 3.14
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, 3 hour Post-Dose, n=109, 29	2.8 nanograms per milliliter	Standard Deviation 3.5
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.7 nanograms per milliliter	Standard Deviation 5.43
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.5 nanograms per milliliter	Standard Deviation 5.27
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 8-14 hour Post-Dose, n=116, 31	3.4 nanograms per milliliter	Standard Deviation 5.68
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 9-15 hour Post-Dose, n=116, 31	3.2 nanograms per milliliter	Standard Deviation 5.42
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, Pre-Dose, n=111, 29	1.4 nanograms per milliliter	Standard Deviation 2.65
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, 1 hour Post-Dose, n=110, 28	2.3 nanograms per milliliter	Standard Deviation 3.69
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, 2 hour Post-Dose, n=109, 29	3.9 nanograms per milliliter	Standard Deviation 5.03
rhEPO-Naive GSK1278863	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, 3 hour Post-Dose, n=109, 29	4.7 nanograms per milliliter	Standard Deviation 5.43
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter	Standard Deviation 0.69
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 7-13 hour Post-Dose, n=117, 31	4.0 nanograms per milliliter	Standard Deviation 2.29
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter	Standard Deviation 1.69
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, Pre-Dose, n=111, 29	0.4 nanograms per milliliter	Standard Deviation 0.42
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 7-13 hour Post-Dose, n=117, 31	0.8 nanograms per milliliter	Standard Deviation 1.22
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 6-12 hour Post-Dose, n=116, 31	4.5 nanograms per milliliter	Standard Deviation 3.14
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.6 nanograms per milliliter	Standard Deviation 5.49
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, 1 hour Post-Dose, n=110, 28	0.5 nanograms per milliliter	Standard Deviation 0.4
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.6 nanograms per milliliter	Standard Deviation 4.6
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 8-14 hour Post-Dose, n=116, 31	3.8 nanograms per milliliter	Standard Deviation 2.31
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, Pre-Dose, n=111, 29	0.3 nanograms per milliliter	Standard Deviation 0.92
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, 2 hour Post-Dose, n=109, 29	1.0 nanograms per milliliter	Standard Deviation 0.71
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, 1 hour Post-Dose, n=110, 28	19.8 nanograms per milliliter	Standard Deviation 19.66
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, Pre-Dose, n=111, 29	1.2 nanograms per milliliter	Standard Deviation 1.25
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, 2 hour Post-Dose, n=109, 29	19.4 nanograms per milliliter	Standard Deviation 21.92
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 20, 3 hour Post-Dose, n=109, 29	1.2 nanograms per milliliter	Standard Deviation 0.88
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK1278863, Wk 20, 3 hour Post-Dose, n=109, 29	13.9 nanograms per milliliter	Standard Deviation 19.12
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 9-15 hour Post-Dose, n=116, 31	3.8 nanograms per milliliter	Standard Deviation 2.29
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 6-12 hour Post-Dose, n=116, 31	3.7 nanograms per milliliter	Standard Deviation 2.89
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.9 nanograms per milliliter	Standard Deviation 2.56
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 7-13 hour Post-Dose, n=117, 31	3.2 nanograms per milliliter	Standard Deviation 2.43
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.4 nanograms per milliliter	Standard Deviation 1.08
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 8-14 hour Post-Dose, n=116, 31	2.9 nanograms per milliliter	Standard Deviation 2.54
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, Pre-Dose, n=111, 29	1.4 nanograms per milliliter	Standard Deviation 1.38
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 4, 9-15 hour Post-Dose, n=116, 31	3.1 nanograms per milliliter	Standard Deviation 2.76
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.2 nanograms per milliliter	Standard Deviation 0.99
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, Pre-Dose, n=111, 29	0.8 nanograms per milliliter	Standard Deviation 0.98
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, 2 hour Post-Dose, n=109, 29	3.8 nanograms per milliliter	Standard Deviation 2.95
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, 1 hour Post-Dose, n=110, 28	1.6 nanograms per milliliter	Standard Deviation 1.39
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.1 nanograms per milliliter	Standard Deviation 0.93
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, 2 hour Post-Dose, n=109, 29	3.7 nanograms per milliliter	Standard Deviation 2.98
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, 1 hour Post-Dose, n=110, 28	1.6 nanograms per milliliter	Standard Deviation 1.29
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2391220, Wk 20, 3 hour Post-Dose, n=109, 29	4.7 nanograms per milliliter	Standard Deviation 3.53
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 4, 9-15 hour Post-Dose, n=116, 31	1.2 nanograms per milliliter	Standard Deviation 1.12
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 8-14 hour Post-Dose, n=116, 31	3.7 nanograms per milliliter	Standard Deviation 2.72
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter	Standard Deviation 0.96
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, Pre-Dose, n=111, 29	0.3 nanograms per milliliter	Standard Deviation 0.38
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 7-13 hour Post-Dose, n=116, 31	0.7 nanograms per milliliter	Standard Deviation 0.7
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, 2 hour Post-Dose, n=109, 29	2.5 nanograms per milliliter	Standard Deviation 1.85
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 8-14 hour Post-Dose, n=116, 31	0.6 nanograms per milliliter	Standard Deviation 0.66
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, 1 hour Post-Dose, n=110, 28	0.6 nanograms per milliliter	Standard Deviation 0.54
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 4, 9-15 hour Post-Dose, n=116, 31	0.8 nanograms per milliliter	Standard Deviation 1.16
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, 1 hour Post-Dose, n=110, 28	1.9 nanograms per milliliter	Standard Deviation 1.38
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, Pre-Dose, n=111, 29	0.1 nanograms per milliliter	Standard Deviation 0.31
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, 2 hour Post-Dose, n=109, 29	1.5 nanograms per milliliter	Standard Deviation 1.22
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, 1 hour Post-Dose, n=110, 28	1.0 nanograms per milliliter	Standard Deviation 1.09
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 20, 3 hour Post-Dose, n=109, 29	3.2 nanograms per milliliter	Standard Deviation 2.22
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, 2 hour Post-Dose, n=109, 29	2.7 nanograms per milliliter	Standard Deviation 2.21
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531398, Wk 20, 3 hour Post-Dose, n=109, 29	2.0 nanograms per milliliter	Standard Deviation 1.57
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2487818, Wk 20, 3 hour Post-Dose, n=109, 29	3.1 nanograms per milliliter	Standard Deviation 2.56
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 4, 9-15 hour Post-Dose, n=116, 31	3.8 nanograms per milliliter	Standard Deviation 3.01
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 6-12 hour Post-Dose, n=116, 31	1.2 nanograms per milliliter	Standard Deviation 0.65
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Day 1, Pre-Dose, n=128, 35	0.0 nanograms per milliliter	Standard Deviation 0
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 7-13 hour Post-Dose, n=117, 31	1.1 nanograms per milliliter	Standard Deviation 0.61
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531401, Wk 4, 6-12 hour Post-Dose, n=116, 31	4.3 nanograms per milliliter	Standard Deviation 2.55
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2506102, Wk 4, 8-14 hour Post-Dose, n=116, 31	1.0 nanograms per milliliter	Standard Deviation 0.61
rhEPO-Naive Control	Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint	GSK2531403, Wk 20, 3 hour Post-Dose, n=109, 29	4.9 nanograms per milliliter	Standard Deviation 3.75

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.

Time frame: Baseline to Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)	7.27 International Units per liter	Standard Deviation 12.744
rhEPO-Naive Control	Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)	27.05 International Units per liter	Standard Deviation 94.999
rhEPO-User GSK1278863	Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)	3.69 International Units per liter	Standard Deviation 20.554
rhEPO-User Control	Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)	25.85 International Units per liter	Standard Deviation 38.89

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.

Time frame: Baseline and up to Week 24

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

Arm	Measure	Value (GEOMETRIC_MEAN)
rhEPO-Naive GSK1278863	Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)	76.36 percent change in VEGF concentration
rhEPO-Naive Control	Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)	26.84 percent change in VEGF concentration
rhEPO-User GSK1278863	Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)	49.99 percent change in VEGF concentration
rhEPO-User Control	Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)	40.85 percent change in VEGF concentration

Secondary

Mean Final 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.

Time frame: Up to 24 Weeks

Population: ITT population.

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Mean Final Dose of GSK1278863 up to 24 Weeks	1.75 milligrams per day	Standard Deviation 1.809
rhEPO-Naive Control	Mean Final Dose of GSK1278863 up to 24 Weeks	1.86 milligrams per day	Standard Deviation 1.692

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.

Time frame: From Week 4 up to 24 Weeks

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

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Mean Number of Dose Adjustments up to 24 Weeks	1.8 number of adjustments	Standard Deviation 0.82
rhEPO-Naive Control	Mean Number of Dose Adjustments up to 24 Weeks	1.7 number of adjustments	Standard Deviation 0.72

Secondary

Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks

Time frame: Up to 24 Weeks

Population: ITT population.

Arm	Measure	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks	249.75 milligrams	Standard Deviation 186.921
rhEPO-Naive Control	Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks	320.42 milligrams	Standard Deviation 214.865

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).

Time frame: Up to 24 weeks

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

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Dose Cycles up to 24 Weeks	1 number

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.

Time frame: Up to 24 Weeks

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

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Hemoglobin (Hgb) Cycles up to 24 Weeks	3 number of Hgb cycles

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.

Time frame: Up to 24 Weeks.

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

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Hemoglobin (Hgb) Excursions	26 number of excursions
rhEPO-Naive Control	Number of Hemoglobin (Hgb) Excursions	10 number of excursions
rhEPO-User GSK1278863	Number of Hemoglobin (Hgb) Excursions	4 number of excursions
rhEPO-User Control	Number of Hemoglobin (Hgb) Excursions	9 number of excursions

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.

Time frame: Over a period of 24 Weeks

Population: ITT population.

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants Reaching Pre-defined Hgb Stopping Criteria	0 Participants
rhEPO-Naive Control	Number of Participants Reaching Pre-defined Hgb Stopping Criteria	0 Participants
rhEPO-User GSK1278863	Number of Participants Reaching Pre-defined Hgb Stopping Criteria	0 Participants
rhEPO-User Control	Number of Participants Reaching Pre-defined Hgb Stopping Criteria	0 Participants

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.)

Time frame: From Day 1 up to Week 28

Population: ITT Population

Arm	Measure	Group	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Blood Transfusions	3 participants
rhEPO-Naive GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	IV Iron	20 participants
rhEPO-Naive GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Inadvertent rhEPO use	4 participants
rhEPO-Naive GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Rescue rhEPO	1 participants
rhEPO-Naive Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	IV Iron	3 participants
rhEPO-Naive Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Inadvertent rhEPO use	NA participants
rhEPO-Naive Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Rescue rhEPO	NA participants
rhEPO-Naive Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Blood Transfusions	1 participants
rhEPO-User GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Inadvertent rhEPO use	9 participants
rhEPO-User GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	IV Iron	3 participants
rhEPO-User GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Rescue rhEPO	0 participants
rhEPO-User GSK1278863	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Blood Transfusions	1 participants
rhEPO-User Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Rescue rhEPO	NA participants
rhEPO-User Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	IV Iron	4 participants
rhEPO-User Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Blood Transfusions	0 participants
rhEPO-User Control	Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline	Inadvertent rhEPO use	NA participants

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

Time frame: Up to 24 weeks

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

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants With at Least One Dose Cycle up to 24 Weeks	1 participants
rhEPO-Naive Control	Number of Participants With at Least One Dose Cycle up to 24 Weeks	0 participants

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.

Time frame: Up to 24 weeks

Population: Completers population.

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks	3 participants
rhEPO-Naive Control	Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks	0 participants
rhEPO-User GSK1278863	Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks	0 participants
rhEPO-User Control	Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks	0 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.

Time frame: Up to 24 weeks

Population: Completers population.

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.	23 participants
rhEPO-Naive Control	Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.	10 participants
rhEPO-User GSK1278863	Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.	4 participants
rhEPO-User Control	Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks.	8 participants

Secondary

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

Time frame: From week 4 up to 24 weeks

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

Arm	Measure	Group	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Twice	50 participants
rhEPO-Naive GSK1278863	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Four times	4 participants
rhEPO-Naive GSK1278863	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Thrice	8 participants
rhEPO-Naive GSK1278863	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Five times or more	1 participants
rhEPO-Naive GSK1278863	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Once	39 participants
rhEPO-Naive Control	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Five times or more	0 participants
rhEPO-Naive Control	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Once	11 participants
rhEPO-Naive Control	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Twice	11 participants
rhEPO-Naive Control	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Thrice	4 participants
rhEPO-Naive Control	Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency	Four times	0 participants

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.

Time frame: Week 24

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

Arm	Measure	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	78 participants
rhEPO-Naive Control	Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	20 participants
rhEPO-User GSK1278863	Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	22 participants
rhEPO-User Control	Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24	19 participants

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.

Time frame: From Week 4 up to Week 24

Population: ITT population.

Arm	Measure	Group	Value (NUMBER)
rhEPO-Naive GSK1278863	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>0-4 Weeks	4 participants
rhEPO-Naive GSK1278863	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>8-12 Weeks	8 participants
rhEPO-Naive GSK1278863	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>4-8 Weeks	8 participants
rhEPO-Naive GSK1278863	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>12 Weeks	1 participants
rhEPO-Naive GSK1278863	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	0 Weeks	102 participants
rhEPO-Naive Control	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>12 Weeks	0 participants
rhEPO-Naive Control	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	0 Weeks	30 participants
rhEPO-Naive Control	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>0-4 Weeks	2 participants
rhEPO-Naive Control	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>4-8 Weeks	0 participants
rhEPO-Naive Control	Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit	>8-12 Weeks	0 participants

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.

Time frame: Weeks 12 to 24

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

Arm	Measure	Group	Value (MEAN)	Dispersion
rhEPO-Naive GSK1278863	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time within target range	68.99 percentage of days	Standard Deviation 34.612
rhEPO-Naive GSK1278863	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time below target range	8.17 percentage of days	Standard Deviation 20.301
rhEPO-Naive GSK1278863	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time above target range	22.84 percentage of days	Standard Deviation 33.825
rhEPO-Naive Control	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time within target range	51.01 percentage of days	Standard Deviation 41.403
rhEPO-Naive Control	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time below target range	3.89 percentage of days	Standard Deviation 16.175
rhEPO-Naive Control	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time above target range	45.10 percentage of days	Standard Deviation 42.579
rhEPO-User GSK1278863	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time above target range	17.96 percentage of days	Standard Deviation 28.809
rhEPO-User GSK1278863	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time within target range	75.06 percentage of days	Standard Deviation 32.485
rhEPO-User GSK1278863	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time below target range	6.98 percentage of days	Standard Deviation 21.118
rhEPO-User Control	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time within target range	61.29 percentage of days	Standard Deviation 43.352
rhEPO-User Control	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time below target range	7.61 percentage of days	Standard Deviation 25.113
rhEPO-User Control	Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24	Percentage of time above target range	31.10 percentage of days	Standard Deviation 41.683

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (GEOMETRIC_MEAN)
rhEPO-Naive GSK1278863	Percent Change From Baseline in Hepcidin Concentration at Week 24	-19.27 percent change in Hepcidin
rhEPO-Naive Control	Percent Change From Baseline in Hepcidin Concentration at Week 24	6.67 percent change in Hepcidin
rhEPO-User GSK1278863	Percent Change From Baseline in Hepcidin Concentration at Week 24	-9.87 percent change in Hepcidin
rhEPO-User Control	Percent Change From Baseline in Hepcidin Concentration at Week 24	-17.12 percent change in Hepcidin

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.

Time frame: Baseline and Week 24

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

Arm	Measure	Value (GEOMETRIC_MEAN)
rhEPO-Naive GSK1278863	Percent Change From Baseline in Transferrin Saturation at Week 24	-1.1 percent change
rhEPO-Naive Control	Percent Change From Baseline in Transferrin Saturation at Week 24	12.3 percent change
rhEPO-User GSK1278863	Percent Change From Baseline in Transferrin Saturation at Week 24	-15.7 percent change
rhEPO-User Control	Percent Change From Baseline in Transferrin Saturation at Week 24	11.4 percent change

Secondary

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

Time frame: From Week 4 up to Week 20

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

Arm	Measure	Group	Value (NUMBER)
rhEPO-Naive GSK1278863	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 8	24 Participants
rhEPO-Naive GSK1278863	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 16	30 Participants
rhEPO-Naive GSK1278863	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 12	30 Participants
rhEPO-Naive GSK1278863	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 20	22 Participants
rhEPO-Naive GSK1278863	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 4	78 Participants
rhEPO-Naive Control	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 20	5 Participants
rhEPO-Naive Control	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 4	21 Participants
rhEPO-Naive Control	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 8	6 Participants
rhEPO-Naive Control	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 12	7 Participants
rhEPO-Naive Control	Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20	Week 16	6 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

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Summary of Hemoglobin (Hgb) Concentration at Week 24

Change From Baseline in Ferritin Concentration at Week 24

Change From Baseline in Hematocrit at Week 24

Change From Baseline in Red Blood Cell Count at Week 24

Change From Baseline in Reticulocyte Cell Count at Week 24

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

Change From Baseline in Total Iron at Week 24

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

Change From Baseline in Transferrin Concentration at Week 24

Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint

Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)

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

Mean Final Dose of GSK1278863 up to 24 Weeks

Mean Number of Dose Adjustments up to 24 Weeks

Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks

Number of Dose Cycles up to 24 Weeks

Number of Hemoglobin (Hgb) Cycles up to 24 Weeks

Number of Hemoglobin (Hgb) Excursions

Number of Participants Reaching Pre-defined Hgb Stopping Criteria

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

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

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

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

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

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

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

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

Percent Change From Baseline in Hepcidin Concentration at Week 24

Percent Change From Baseline in Transferrin Saturation at Week 24

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