Efficacy and Safety Study of GSK1278863 in Japanese Hemod... | NCT02829320

Label	Type	Description	Intervention Names
GSK1278863	Experimental	Subjects will receive GSK1278863 once daily orally at a starting dose of 4 milligrams (mg) on Day 1, and continued until the day of Week 4. From Weeks 4 to 24, interruption of treatment or dose adjustments will be made within the maintenance dose range of 1 mg to 24 mg according to the dose adjustment algorithm to achieve and/or maintain Hgb within the target range (10.0 to 12.0 g/dL) based on the Hgb value measured every 4 weeks. Dose changes will be made every 4 weeks. Iron replacement therapy will be given according to the standard starting criteria.	Drug: GSK1278863 Drug: Iron

Name	Type	Description	Arm Group Labels	Other Names
GSK1278863	Drug	GSK1278863 will be provided as round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, 4 mg or 6 mg of GSK1278863 as active ingredient.	GSK1278863

Measure	Description	Time Frame
Change From Baseline in Hgb at Week 4	Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The analysis was performed on All Treated Subjects Population which comprised of all participants who received at least one dose of GSK1278863.	Baseline and Week 4
Number of Participants by Hgb Change From Baseline Category at Week 4	Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The change in Hgb at Week 4 was classified into different categories (i.e., <=-2.0, >-2.0 to -1.0, >-1.0 to 0, >0 to 1.0, >1.0 to 2.0, and >2 g/dL), and the number of participants in each category were summarized.	Baseline and Week 4

Measure	Description	Time Frame
Hgb Values at the Indicated Time Points	Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer.	Up to Week 24
Change From Baseline in Hgb at the Indicated Time Points

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age (at the time of informed consent): >=20 years
Dialysis: Patients on hemodialysis (HD) or hemodiafiltration (HDF)
Use of any erythropoiesis stimulating agent (ESA): Newly started dialysis (Dialysis newly started <12 weeks before screening): Patients not using ESAs after the start of dialysis; Maintenance dialysis (Dialysis started >=12 weeks before screening): Patients not using ESAs within 8 weeks before screening (including interruption of ESA therapy)
Hemoglobin (Hgb): >=8.0 to <10.0 g/dL (measured using a point-of-care Hgb measurement device at the study site on Day 1)
Iron parameter: Ferritin >100 nanograms (ng)/milliliter (mL) or transferrin saturation (TSAT) >20% (at screening only)
Gender (at screening only): Female or male.

A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin [hCG] test for females of reproductive potential [FRP] only), not breastfeeding, and at least one of the following conditions applies:

Females of non-reproductive potential defined as: Pre-menopausal with one of the following and no plans to utilise assisted reproductive techniques (example [e.g.], in vitro fertilisation or donor embryo transfer): documented bilateral tubal ligation or salpingectomy; documented hysteroscopic tube occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy
Post-menopausal defined as females 60 years of age or older or In females <60 years of age, 12 months of spontaneous amenorrhea (In questionable cases, a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause is confirmatory [the reference values are provided separately]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective 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 enrollment.

Females of reproductive potential who agree to follow one of the options listed in the "GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential" from 28 days before the first dose of study treatment until completion of the follow-up visit.

Informed consent: Subjects who can provide written informed consent to the study, involving compliance with the requirements and patient responsibilities stated in the consent form and the protocol.

Exclusion Criteria:

CKD related criteria

Kidney transplant: Planned living kidney transplant during the study period Anemia-related criteria
Aplasia: History of bone marrow aplasia or pure red cell aplasia
Other causes of anemia: Pernicious anemia, thalassaemia, sickle cell disease, or myelodysplastic syndrome
Gastrointestinal bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding within 8 weeks before screening or during a period from screening to Day 1.

Cardiovascular disease-related criteria

History of myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack: Diagnosed within 8 weeks before screening or during a period from screening to Day 1.
Heart failure: Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system
Corrected QT interval (QTc) (at screening only): QTc >500 milliseconds (msec), or QTc >530 msec in subject with bundle branch block. Note: Corrected QT interval using Bazett's formula (QTcB) (machine-read or manually) will be used.

Other disease-related criteria

Liver disease (if any of the following occurs):
- Alanine transaminase (ALT) >2x upper limit of normal (ULN)
- Bilirubin >1.5xULN (If bilirubin fractions are measured and direct bilirubin is <35%, isolated bilirubin >1.5xULN will be acceptable.)
- Current unstable active liver or biliary disease (generally defined by the onset of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, persistent jaundice, or cirrhosis). Note: The only exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated >=8 weeks before screening.
Malignancy: History of malignancy within the two years prior to screening, known complex kidney cyst >3 centimeters (cm) (II F, III or IV based on the Bosniak classification) or currently receiving treatment for cancer. Note: The only exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated >=8 weeks before screening.

Concomitant medications and other study treatment-related criteria

Iron medication: Planned use of any intravenous iron during the screening period or from Day 1 to Week 4.

Note:

Patients on oral iron may be enrolled if the iron dose regimen is unchanged during the screening period and from Day 1 to Week 4.
Patients on anti-hyperphosphatemia medication containing iron (e.g., ferric citrate hydrate) for at least 12 weeks before screening may be enrolled if the medication is continued during the screening and from Day 1 to Week 4.
- Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to any excipients in the investigational product
- Drugs and dietary supplements: Current use of prohibited prescription drugs, non-prescription drugs, or dietary supplements or planned use of any of these drugs during the study period (prohibited drugs: strong cytochrome P450 (CYP)2C8 inducers and inhibitors)
- Exposure to any other investigational product: Use of an investigational product within the past 30 days or five half lives of that investigational product (whichever is longer).
- Prior treatment with GSK1278863: Prior treatment with GSK1278863 for >30 days 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, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Aichi		455-8530	Japan
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
31306555	Background	Tsubakihara Y, Akizawa T, Nangaku M, Onoue T, Yonekawa T, Matsushita H, Endo Y, Cobitz A. A 24-Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients. Ther Apher Dial. 2020 Apr;24(2):108-114. doi: 10.1111/1744-9987.12962. Epub 2019 Aug 13.

ID	Title	Description
FG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 milligram (mg) for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain hemoglobin (Hgb) within the target range (10.0-12.0 grams per deciliter [g/dL]). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 nanogram per milliliter (ng/mL) and transferrin saturation (TSAT) is <=20%.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 19, 2017	Mar 21, 2018

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 Hgb at Week 4

Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The analysis was performed on All Treated Subjects Population which comprised of all participants who received at least one dose of GSK1278863.

All Treated Subjects Population

Posted

Mean

95% Confidence Interval

G/dL

Baseline and Week 4

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG00028

Title

Denominators

Categories

Title	Measurements
	OG0000.79(0.53 to 1.05)

Primary

Number of Participants by Hgb Change From Baseline Category at Week 4

Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The change in Hgb at Week 4 was classified into different categories (i.e., <=-2.0, >-2.0 to -1.0, >-1.0 to 0, >0 to 1.0, >1.0 to 2.0, and >2 g/dL), and the number of participants in each category were summarized.

All Treated Subjects Population

Posted

Count of Participants

Participants

Baseline and Week 4

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Hgb Values at the Indicated Time Points

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer.

All Treated Subjects Population

Posted

Mean

Standard Deviation

G/dL

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Hgb at the Indicated Time Points

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The Baseline value was the latest pre-dose assessment. Change from Baseline at indicated time-points was calculated by subtracting Baseline value from the post-dose visit value.

All Treated Subjects Population

Posted

Mean

Standard Deviation

G/dL

Baseline and up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Number of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL)

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants with Hgb withinthe target range (10.0 to 12.0 g/dL) at each assessment visit was summarized.

All Treated Subjects Population

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Time to Reach the Lower Target Hgb Level (10.0 g/dL)

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. Participants who could not reach lower target were regarded as censored. The time (in days) to reach the lower target Hgb level (10.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method.

All Treated Subjects Population

Posted

Median

Inter-Quartile Range

Days

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Number of Participants Who Had Hgb Level of Less Than 7.5 g/dL

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of less than 7.5 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

All Treated Subjects Population

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Number of Participants Who Had Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb increase of more than 2.0 g/dL over any 4 weeks were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

All Treated Subjects Population

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Number of Participants Who Had Hgb Level of More Than 13.0 g/dL

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

All Treated Subjects Population

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Number of Episodes of Achieving Hgb Level of More Than 13.0 g/dL

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of episodes in participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

All Treated Subjects Population

Posted

Number

Episodes

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863

Blood samples were collected to evaluate AUC (0-4) at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Population consisted of all participants who received GSK1278863 with the PK samples collected and analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*nanogram per milliliter (h*ng/mL)

1, 2, 3 and 4 hours post dose at Weeks 12 and 24

ID	Title	Description
OG000	GSK1278863 1 mg	Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 1 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
OG001	GSK1278863 2 mg	Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 2 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Secondary

Maximum Observed Concentration (Cmax) of GSK1278863

Blood samples were collected to evaluate Cmax at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1.

PK Population

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

1, 2, 3 and 4 hours post dose at Weeks 12 and 24

ID	Title	Description
OG000	GSK1278863 1 mg	Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 1 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.
OG001	GSK1278863 2 mg	Participants received GSK1278863 orally once daily initially at 4 mg from Day 1 in 4-week fixed-dose period. Participants received GSK1278863 2 mg orally at specified visits just before collecting the PK samples. As PK samples were collected more than once, participants might be included in more than one arm. In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Secondary

Monthly Average Dose of Intravenous (IV) Iron During the Treatment Period

Records of on-therapy iron medication were used to calculate average quarterly IV iron dose. Quarter 1 = (Randomization Date - Treatment Start Date at Week 12 - 1 [day]). Quarter 2 = (Treatment Start Date at Week 12 - Study Treatment Stop Date). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

All Treated Subjects Population

Posted

Mean

Standard Deviation

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Number of Participants Who Used Iron During the Treatment Period

The number of participants who used iron (both IV and oral iron) during the treatment period were summarized.

All Treated Subjects Population

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Ferritin

Blood samples were collected from participants for measurement of serum ferritin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

All Treated Subjects Population

Posted

Mean

Standard Deviation

Microgram per liter (µg/L)

Baseline and up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in TSAT

Blood samples were collected from participants for measurement of TSAT at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1).

All Treated Subjects Population

Posted

Geometric Mean

95% Confidence Interval

Percentage of transferrin

Baseline and up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Percent Change From Baseline in Hepcidin

Blood samples were collected from participants for measurement of hepcidin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). If a laboratory value had a non-detectable level reported in the database, where the numeric value was missing, the value was not included in a summary. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

All Treated Subjects Population

Posted

Geometric Mean

95% Confidence Interval

Percentage of hepcidin

Baseline and up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Secondary

Change From Baseline in Serum Iron

Blood samples were collected from participants for measurement of serum iron at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

All Treated Subjects Population

Posted

Mean

Standard Deviation

Micromoles per liter (µmol/L)

Baseline and up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Total Iron Binding Capacity (TIBC)

Blood samples were collected from participants for measurement of TIBC at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

All Treated Subjects Population

Posted

Mean

Standard Deviation

umol/L

Baseline and up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Dose Level of GSK1278863 at Indicated Time Points

Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. Mean dose during Week 12 to 24 is the average of dose at Weeks 12, 16, and 20.

All Treated Subjects Population

Posted

Median

Full Range

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Frequency of Dose Adjustments

Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. For dose adjustments frequency, the number of participants were provided by the number of dose adjustments (i.e. zero, one, two, three, four, and five or more).

All Treated Subjects Population

Posted

Count of Participants

Participants

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants

Secondary

Duration of Treatment Interruption Due to Hgb >13 g/dL

Hgb values were used for making decision of treatment interruption. On-therapy Hgb values observed in both scheduled and unscheduled visits were counted. Participants who have no treatment interruption due to Hgb >13.0 g/dL are not included

All Treated Subjects Population

Posted

Median

Full Range

Days

Up to Week 24

ID	Title	Description
OG000	All Participants	Participants with newly started dialysis (dialysis newly started <12 weeks before screening) or with maintenance dialysis (dialysis started >=12 weeks before screening) received GSK1278863 orally once daily initially at 4 mg for 4 weeks from Day 1. Subsequently, participants received GSK1278863 orally once a day according to a pre-defined study treatment dose adjustment algorithm to achieve or maintain Hgb within the target range (10.0-12.0 g/dL). In participants taking oral iron before the study, their iron dose was not changed during the fixed-dose period. Supplemental iron therapy was administered if ferritin is <=100 ng/mL and TSAT is <=20%.

Units	Counts
Participants	OG000

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Shunt occlusion	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment		EG0003 events2 affected28 at risk
Device dislocation	Product Issues	MedDRA 20.1	Systematic Assessment		EG0001 events1 affected28 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG00010 events9 affected28 at risk
Infected dermal cyst	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0003 events2 affected28 at risk
Shunt stenosis	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected28 at risk

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
D019216	Metals, Heavy
D004602	Elements
D007287	Inorganic Chemicals
D028561	Transition Elements
D008670	Metals