Evaluation of Dose Response Relationship, Safety and Effi... | NCT01977482

Label	Type	Description	Intervention Names
GSK1278863 4 mg	Experimental	Subjects will take GSK1278863 4 mg blinded once daily (OD) orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24.	Drug: GSK1278863
GSK1278863 6 mg	Experimental	Subjects will take GSK1278863 6 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24.	Drug: GSK1278863
GSK1278863 8 mg	Experimental	Subjects will take GSK1278863 8 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24.	Drug: GSK1278863
GSK1278863 10 mg	Experimental	Subjects will take GSK1278863 10 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24.	Drug: GSK1278863
GSK1278863 12 mg	Experimental

Name	Type	Description	Arm Group Labels	Other Names
GSK1278863	Drug	Film coated tablets containing 1 mg, 2 mg, 5 mg, or 25 mg of GSK1278863	GSK1278863 10 mg GSK1278863 12 mg GSK1278863 4 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin (Hgb) at Week 4	Baseline Hgb value was the average of three Hgb values taken during screening period at Week (W) -4, W-2 and Day 1. Change from Baseline in Hgb was calculated as W4 value minus the Baseline value. To model the dose-response relationship a four-parameter Emax model was used. The dose response dataset was based on all non-missing data collected up to W4. Participants (par.) who had a Week 2 Hgb measurement, but a missing Week 4 Hgb measurement were included with a change from Baseline at Week 4 value imputed as twice the change from Baseline at Week 2. E0 is the expected Hgb change from Baseline for a par. receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a par. receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Alpha is the coefficient of the model covariate for centred Baseline.	Baseline (Week -4, Week-2 and Day 1) and Week 4

Secondary Outcomes

Measure	Description	Time Frame
Hgb Concentration at Week 24	Hgb values measured at Week 24 are presented.	Week 24
Percentage of Time Within, Below, and Above Hgb Target Range Between Weeks 20 and 24	The percentage of time in Hgb target range between Weeks 20 and 24 for a participant was calculated by dividing the total number of days that Hgb was within the target range (10.0 to 11.5 g/dL) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the participant remained on treatment during the defined period. Similarly, percentage of time above Hgb target range and percentage of time below Hgb target range were calculated.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

- Subjects are eligible if they meet all of the inclusion criteria below:
General 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 [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 International units per liter (IU/L) and estradiol <=10 picomole per liter (pmol/L) is confirmatory]. 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. For most forms of HRT, at least 2 weeks must elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method;
Q-T Interval Corrected for Heart Rate (QTc): Bazett's Correction of QT Interval (QTcB) <470 millisecond (msec) or QTcB <480 msec in subjects with bundle branch block. There is no QTc inclusion criterion for a subject with a predominantly paced rhythm.
CKD-related criteria
Dialysis frequency: On hemodialysis (HD) three to five times weekly for at least 4 weeks prior to Week -4 Screening through Week 4. NOTE: Combination methods including hemofiltration (HF) or ultrafiltration (UF) with HD are allowed. However, the type of dialysis (HD, hemodiafiltration (HDF) or UF) should not change during the study.
Dialysis adequacy: A single-pool dialyzer clearance multiplied by dialyzer time divided by volume of distribution of urea (Kt/Vurea) of >=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%. NOTE: Only needs confirming at Week -4.
Hemoglobin: Baseline Hgb of 9.0-11.5 g/dL (may rescreen in a minimum of 2 weeks).
Stable rhEPO dose: Using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses varying 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.
Iron replacement therapy: Subjects may be on stable maintenance oral or IV (<=100 mg/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Week -4, during the screening phase, and through the first 4 weeks after Randomization.

Exclusion Criteria:

Subjects are not eligible if they meet any of the exclusion criteria below:
CKD-related criteria
Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
Renal transplant: Pre-emptive or scheduled renal transplant.
High rhEPO dose: An epoetin dose of >=360 IU/Kg/Week IV or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram (µg)/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).
Laboratory test-based criteria (Week -4 verification only)
Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
Folate: <2.0 nanogram (ng)/mL (<4.5 nanomole (nmol)/L) (may rescreen in a minimum of 4 weeks).
Ferritin: <100 ng/mL (<100 Micrograms per liter).
Transferrin saturation (TSAT): Outside of the reference range.
Cardiovascular disease-related criteria
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).
Hypertension: Defined using pre-dialysis vitals (Week -4, Day 1) of diastolic blood pressure (DBP) >100 millimeters of mercury (mmHg) or systolic blood pressure (SBP) >170 mmHg.
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).
Other disease-related criteria
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. NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not met.
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.
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 intravenous (IV) antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed.
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).
Concomitant medication and other Investigational Product-related criteria
Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
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).
General health-related criteria
Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the Investigator considers would put the subject at unacceptable risk.
Pregnancy or Lactation: Pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or during the trial.
Other Eligibility Criteria Considerations
Laboratory eligibility criteria will be assessed according to the central laboratory results for the screening samples.
Subjects who fail screening may be rescreened as soon as the investigator feels they may have become eligible. However, an individual subject may not rescreen more than twice. There is no predetermined amount of time that the investigator needs to wait to rescreen a previously ineligible subject, except those excluded for Hgb or folate who may only rescreen in 2 and 4 weeks, respectively, and those excluded for Vitamin B12 who may rescreen in 8 weeks

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Azusa	California	91702	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	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
FG001	GSK1278863 4 mg

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

Change From Baseline in Hemoglobin (Hgb) at Week 4

Baseline Hgb value was the average of three Hgb values taken during screening period at Week (W) -4, W-2 and Day 1. Change from Baseline in Hgb was calculated as W4 value minus the Baseline value. To model the dose-response relationship a four-parameter Emax model was used. The dose response dataset was based on all non-missing data collected up to W4. Participants (par.) who had a Week 2 Hgb measurement, but a missing Week 4 Hgb measurement were included with a change from Baseline at Week 4 value imputed as twice the change from Baseline at Week 2. E0 is the expected Hgb change from Baseline for a par. receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a par. receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Alpha is the coefficient of the model covariate for centred Baseline.

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

Posted

Mean

Standard Deviation

grams (g)/deciliter (dL)

Baseline (Week -4, Week-2 and Day 1) and Week 4

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG003	GSK1278863 8 mg	Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG004	GSK1278863 10 mg	Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG005	GSK1278863 12 mg	Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Units	Counts
Participants	OG00039 OG00139 OG00240 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.64± 0.829 OG001-0.24± 0.989 OG0020.08± 1.131 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004 OG005						E0 (g/dL)	-0.664			2-Sided	95	-0.960	-0.387			Posterior median and 95% credibility intervals were estimated using Bayesian methods.		Superiority or Other
OG000 OG001 OG002 OG003 OG004 OG005

Secondary

Hgb Concentration at Week 24

Hgb values measured at Week 24 are presented.

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

Posted

Mean

Standard Deviation

g/dL

Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG003	GSK1278863 8 mg

Secondary

Percentage of Time Within, Below, and Above Hgb Target Range Between Weeks 20 and 24

The percentage of time in Hgb target range between Weeks 20 and 24 for a participant was calculated by dividing the total number of days that Hgb was within the target range (10.0 to 11.5 g/dL) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the participant remained on treatment during the defined period. Similarly, percentage of time above Hgb target range and percentage of time below Hgb target range were calculated.

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

Posted

Mean

Standard Deviation

Percentage of days

Week 20 to Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg

Secondary

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

The number of participants with Hgb in the target range of 10.0 to 11.5 g/dL at Week 24 was recorded for each arm.

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

Posted

Number

Participants

Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG003	GSK1278863 8 mg

Secondary

Number of Participants Reaching Pre-defined Hgb Stopping Criteria

The number of participants who reached the Hgb stopping criteria of Hgb concentration <7.5 g/dL were presented.

ITT Population

Posted

Number

Participants

Up to 24 weeks

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG003	GSK1278863 8 mg

Secondary

Maximum Observed Change From Baseline in Erythropoietin (EPO)

Blood samples for control arm were collected on Day 1 (pre-dose), Week 4 (5-15 minutes post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 5-15 minutes post-dose), Week 24 (pre-dose), and Week 28 (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-dose values minus the Baseline value.

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

Posted

Mean

Standard Deviation

international units(IU)/Liter (L)

Baseline (Day 1) to Week 28

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

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

Blood samples for control arm were collected on Day 1 (pre-dose), Week 4 (5-15 minutes post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 5-15 minutes post-dose), Week 24 (pre-dose), and Week 28 (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 percent change from Baseline in VEGF was recorded for each arm. Baseline value for VEGF is the pre-dose value on Day 1. Percent change from Baseline was calculated as 100 multiplied by exponential of mean change in log scale minus 1.

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

Posted

Geometric Mean

95% Confidence Interval

Percent change

Baseline (Day 1) to Week 28

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Population Plasma PK Parameters of GSK1278863 and Metabolites

Blood samples were collected for individual plasma GSK1278863and metabolite (GSK2391220, GSK2499166, GSK2531403, GSK2531400, GSK2531399, and GSK2531398) concentrations measurement on Day (D) 1 (pre-dose [PrD), at Week (W) 4 (6-12, 7-13, 8-14, and 9-15 hour [hr] post-dose [PoD), and at W20 (PrD, 1, 2, and 3 hour PoD). Pharmacokinetic population: All participants from whom a PK sample has been obtained and analyzed.](streamdown:incomplete-link)

Pharmacokinetic Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points; thus, the overall number of participants analyzed reflects everyone in the pharmacokinetic population

Posted

Mean

Standard Deviation

nanograms (ng)/milliliter (mL)

Day 1, Week 4, and Week 20

ID	Title	Description
OG000	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Percent Change From Baseline in Hepcidin at Week 24

Hepcidin is a regulator of iron metabolism. Baseline value for transferrin saturation is the pre-dose value on Day 1. Percent change from Baseline was calculated as 100 multiplied by exponential of mean change in log scale minus 1.

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

Posted

Geometric Mean

95% Confidence Interval

Percent change

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Change From Baseline in Ferritin at Week 24

Baseline value for ferritin is the pre-dose value on Day 1. Change from Baseline in ferritin was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

Micrograms/Liter

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG003

Secondary

Change From Baseline in Transferrin at Week 24

Baseline value for transferrin is the pre-dose value on Day 1. Change from Baseline in transferrin was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

grams (g)/Liter (L)

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Percent Change From Baseline in Transferrin Saturation at Week 24

Transferrin saturation is measured as a percentage, it is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value for transferrin saturation is the pre-dose value on Day 1. Percent change from Baseline =: 100*(exp(Mean change log scale)-1).

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

Posted

Geometric Mean

95% Confidence Interval

Percent change

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Change From Baseline in Total Iron at Week 24

Baseline value for total iron is the pre-dose value on Day 1. Change from Baseline in total iron was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

Micromoles/Liter

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG003

Secondary

Change From Baseline in Total Iron Binding Capacity at Week 24

Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Baseline value for total iron binding capacity is the pre-dose value on Day 1. Change from Baseline in total iron binding capacity was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

Micromoles/Liter

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Change From Baseline in Reticulocyte Hemoglobin at Week 24

Baseline value for reticulocyte hemoglobin is the pre-dose value on Day 1. Change from Baseline in reticulocyte hemoglobin was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

Picogram

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Change From Baseline in Hematocrit at Week 24

Hematocrit is the ratio of the volume of red blood cells to the total volume of blood. Baseline value for hematocrit is the pre-dose value on Day 1. Change from Baseline in hematocrit was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Change From Baseline in Red Blood Cells at Week 24

Baseline value for red blood cells is the pre-dose value on Day 1. Change from Baseline in red blood cells was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

10^12 cells/Liter

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Secondary

Change From Baseline in Reticulocyte Count at Week 24

A reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline value for reticulocyte count is the pre-dose value on Day 1. Change from Baseline in reticulocyte count was calculated as the Week 24 value minus the Baseline value.

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

Posted

Mean

Standard Deviation

Percentage of reticulocytes in blood

Baseline (Day 1) and Week 24

ID	Title	Description
OG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
OG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG0030 affected39 at risk EG0040 affected40 at risk EG0050 affected19 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0021 affected40 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Atrioventricular block	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0012 affected39 at risk EG0020 affected40 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Sick sinus syndrome	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Gastric polyps	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Gastrointestinal angiodysplasia	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Intestinal polyp	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Amyloidosis	Immune system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Device related sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Lobar pneumonia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Peritonitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Pneumonia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Arteriovenous fistula site haemorrhage	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Complications of transplanted kidney	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Dialysis related complication	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Graft thrombosis	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Shunt stenosis	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Shunt thrombosis	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Troponin I increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Pleural mesothelioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Syncope	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Psychotic disorder	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Oligomenorrhoea	Reproductive system and breast disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Uterine inflammation	Reproductive system and breast disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Arteriosclerosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Steal syndrome	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Superior vena cava stenosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0012 affected39 at risk EG0022 affected40 at risk EG0031 affected39 at risk EG0040 affected40 at risk EG0050 affected19 at risk
Cataract	Eye disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0012 affected39 at risk EG0021 affected40 at risk EG003
Periorbital oedema	Eye disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0022 affected40 at risk EG003
Retinal artery embolism	Eye disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Vitreous floaters	Eye disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0014 affected39 at risk EG0020 affected40 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment		EG0002 affected39 at risk EG0015 affected39 at risk EG0022 affected40 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment		EG0002 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0016 affected39 at risk EG0023 affected40 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0012 affected39 at risk EG0020 affected40 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment		EG0001 affected39 at risk EG0013 affected39 at risk EG0022 affected40 at risk EG003
Asthenia	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0000 affected39 at risk EG0012 affected39 at risk EG0023 affected40 at risk EG003
Chills	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0001 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Face oedema	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0002 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0001 affected39 at risk EG0010 affected39 at risk EG0022 affected40 at risk EG003
Pain	General disorders	MedDRA 17.0	Systematic Assessment	General disorders and administration site conditions	EG0000 affected39 at risk EG0012 affected39 at risk EG0020 affected40 at risk EG003
Bronchitis	Infections and infestations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0022 affected40 at risk EG003
Device related infection	Infections and infestations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 17.0	Systematic Assessment		EG0005 affected39 at risk EG0015 affected39 at risk EG0026 affected40 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment		EG0001 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Dialysis related complication	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Procedural site reaction	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Blood pressure increased	Investigations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0023 affected40 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 17.0	Systematic Assessment		EG0002 affected39 at risk EG0011 affected39 at risk EG0020 affected40 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment		EG0001 affected39 at risk EG0012 affected39 at risk EG0021 affected40 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0012 affected39 at risk EG0021 affected40 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0022 affected40 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment		EG0004 affected39 at risk EG0010 affected39 at risk EG0022 affected40 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0012 affected39 at risk EG0022 affected40 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0012 affected39 at risk EG0022 affected40 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Dizziness	Nervous system disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0022 affected40 at risk EG003
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment		EG0002 affected39 at risk EG0014 affected39 at risk EG0021 affected40 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0021 affected40 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment		EG0001 affected39 at risk EG0012 affected39 at risk EG0020 affected40 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0022 affected40 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment		EG0001 affected39 at risk EG0013 affected39 at risk EG0020 affected40 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment		EG0002 affected39 at risk EG0010 affected39 at risk EG0021 affected40 at risk EG003
Haematoma	Vascular disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0010 affected39 at risk EG0020 affected40 at risk EG003
Hypertension	Vascular disorders	MedDRA 17.0	Systematic Assessment		EG0001 affected39 at risk EG0016 affected39 at risk EG0020 affected40 at risk EG003
Hypotension	Vascular disorders	MedDRA 17.0	Systematic Assessment		EG0000 affected39 at risk EG0011 affected39 at risk EG0020 affected40 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

ID	Title	Description
BG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
BG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
BG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
BG003	GSK1278863 8 mg	Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
BG004	GSK1278863 10 mg	Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
BG005	GSK1278863 12 mg	Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.
BG006	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Control	Participants received placebo once daily for the first 4 weeks and thereafter received open label rhEPO as required to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.	11	39	17	39
EG001	GSK1278863 4 mg	Participants received GSK1278863 4 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.	10	39	28	39
EG002	GSK1278863 6 mg	Participants received GSK1278863 6 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.	8	40	17	40
EG003	GSK1278863 8 mg	Participants received GSK1278863 8 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.	8	39	25	39
EG004	GSK1278863 10 mg	Participants received GSK1278863 10 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.	11	40	21	40
EG005	GSK1278863 12 mg	Participants received GSK1278863 12 mg once daily for the first 4 weeks and thereafter, if necessary the dose was adjusted every four weeks to achieve Hgb within the range of 10.0-11.5 g/dL for the remaining 20 weeks.	1	19	6	19