| Outcome Measures: |
Primary: Summary of Hemoglobin (Hgb) Concentration at Week 24, The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. The primary objective was to characterize the ability of GSK1278863 to achieve mean Hgb response within the target range., Week 24 | Secondary: Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24, Target range is defined as: Original Hgb Criteria of 9.0 to 10.5 gram/deciliter (g/dL), and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL., Week 24|Number of Participants Reaching Pre-defined Hgb Stopping Criteria, The Hgb stopping criteria was a value of \<7.5 mg/dL obtained on-site via a validated point-of-care Hgb measurement device, which necessitated permanent discontinuation of the study medication. None of the participants met the stopping criteria therefore there is no data to present for this outcome measure., Over a period of 24 Weeks|Percent Change From Baseline in Hepcidin Concentration at Week 24, Baseline is the last pre-dose hepcidin value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the Week 24 value., Baseline and Week 24|Maximum Observed Change From Baseline in Serum Erythropoietin (EPO), Blood samples for control arm were collected pre-dose for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm. Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-baseline values minus the Baseline value., Baseline to Week 24|Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF), Blood samples for control arm were collected pre-dose for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for VEGF measurement. The maximum observed change from baseline in VEGF was recorded for each arm . Baseline value for VEGF is the pre-dose value on Day 1. Change from Baseline in VEGF was calculated as the individual post-baseline values minus the Baseline value., Baseline and up to Week 24|Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24, The number of days a participant's Hgb was within target range was calculated by estimating (using linear interpolation) the number of days within target range between two scheduled Hgb visits. Percentage of time within range for a participant was calculated by dividing the total number of days that Hgb was within range during Weeks 12 to 24 by the total number of days the participant remained on treatment during Weeks 12 to 24. Similary, percent of time above and below Hgb target range was calculated. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL., Weeks 12 to 24|Change From Baseline in Ferritin Concentration at Week 24, Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value., Baseline and Week 24|Change From Baseline in Transferrin Concentration at Week 24, Baseline is the last pre-dose transferrin value. Change from Baseline in transferrin was calculated by subtracting the Baseline value from the Week 24 value., Baseline and Week 24|Percent Change From Baseline in Transferrin Saturation at Week 24, Transferrin saturation is measured as a percentage; it is a ratio of serum iron and total iron-binding capacity. Baseline is the last pre-dose transferrin saturation value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the post-dose value., Baseline and Week 24|Change From Baseline in Total Iron at Week 24, Baseline is the last pre-dose total iron value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value., Baseline and Week 24|Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24, TIBC measures the blood's capacity to bind iron with transferrin. Baseline is the last pre-dose TIBC value. Change from Baseline in TIBC was calculated by subtracting the Baseline value from the Week 24 value., Baseline and Week 24|Change From Baseline in Reticulocyte Hemoglobin (CHr) at Week 24, Reticulocytes are slightly immature red blood cells. Reticulocyte Hgb content is used to differentiate iron deficiency from other causes of anemia. Baseline is the last pre-dose CHr value. Change from Baseline in reticulocyte Hgb was calculated by subtracting the Baseline value from the post-dose value., Baseline and Week 24|Change From Baseline in Hematocrit at Week 24, Baseline is the last pre-dose hematocrit value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value., Baseline and Week 24|Change From Baseline in Red Blood Cell Count at Week 24, Baseline is the last pre-dose red blood cell count. Change from Baseline in red blood cell count was calculated by subtracting the Baseline count from the post-dose count., Baseline and Week 24|Change From Baseline in Reticulocyte Cell Count at Week 24, Reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline is the last pre-dose red reticulocyte count. Change from Baseline in reticulocyte cell count was calculated by subtracting the Baseline count from the Week 24 count., Baseline and Week 24|Concentration of GSK1278863 and Relevant Metabolites as a Population Pharmacokinetic Endpoint, Blood samples were collected for individual plasma GSK1278863 and metabolite (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531401, and GSK2531403) concentration measurement on Day 1 (pre-dose), Wk 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose). Participants available in each arm at the specified time points have been presented., Day 1 (pre-dose), Week (Wk) 4 (6-12 hour, 7-13 hour, 8-14 hour, 9-15 hour post-dose), and Wk 20 (pre-dose, 1 hour, 2 hour, 3 hour post-dose)|Mean Number of Dose Adjustments up to 24 Weeks, After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system., From Week 4 up to 24 Weeks|Number of Participants With Dose Adjustments up to 24 Weeks, as a Measure of Dose Adjustment Frequency, After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. Frequency is presented as the number of participants with dose adjustment(s) once, twice, thrice, four times, or five times., From week 4 up to 24 weeks|Timing of Dose Adjustments at Weeks 4, 8, 12, 16, and 20, After 4 Weeks, the need to adjust the dose of GSK1278863 was evaluated at every scheduled visit, to maintain hemoglobin within the target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL. Dose adjustments were assigned automatically via the interactive voice/web response system. The number of participants with an adjustment are presented at the timings at which adjustments were done., From Week 4 up to Week 20|Mean Total Cumulative Dose of GSK1278863 up to 24 Weeks, The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL., Up to 24 Weeks|Mean Final Dose of GSK1278863 up to 24 Weeks, The starting dose was kept constant for the first 4 Weeks after randomization. Later, the need to adjust the dose of GSK1288863 was evaluated at every scheduled visit according to a pre-specified algorithm, to achieve and maintain hemoglobin within the specified target range. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL., Up to 24 Weeks|Number of Hemoglobin (Hgb) Excursions, A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter. Hgb cycle is calculated as two consecutive Hgb excursions in different directions., Up to 24 Weeks.|Number of Hemoglobin (Hgb) Cycles up to 24 Weeks, A Hgb cycle is calculated as two consecutive Hgb excursions in different directions. A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter., Up to 24 Weeks|Number of Dose Cycles up to 24 Weeks, A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease)., Up to 24 weeks|Number of Participants With at Least One Hemoglobin (Hgb) Excursion up to 24 Weeks., A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter., Up to 24 weeks|Number of Participants With at Least One Hemoglobin (Hgb) Cycle up to 24 Weeks, A Hgb excursion is a series of decreasing or increasing Hgb values differing by \>=1.5 grams per deciliter. A Hgb cycle is two consecutive Hgb excursions in different directions., Up to 24 weeks|Number of Participants With at Least One Dose Cycle up to 24 Weeks, A dose cycle is a series of three directional dose changes (that is, increase, decrease, increase; or decrease, increase, decrease). participants, Up to 24 weeks|Number of Participants Receiving Additional Therapies of Blood Transfusions, Intravenous (IV) Iron or rhEPO at Any Time Post-Baseline, Participants receiving additional therapies of blood transfusions, intravenous (IV) iron or rhEPO any time Post Baseline were analyzed. RhEPO was not applicable for the control arms since it was a planned therapy in those arms, hence presented as NA. (EudraCT only: A value of 99999 is used where no data is available or NA.), From Day 1 up to Week 28|Number of Weeks Dose Withheld Because Hemoglobin (Hgb) Exceeded the Upper Limit, Number of Weeks dose was withheld because hemoglobin exceed the upper limit is presented as the number of participants with withheld dose during the time periods categorized by Weeks., From Week 4 up to Week 24
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| Locations: |
GSK Investigational Site, Peoria, Arizona, 85381, United States|GSK Investigational Site, Azusa, California, 91702, United States|GSK Investigational Site, La Mesa, California, 91942, United States|GSK Investigational Site, Laguna Hills, California, 92653, United States|GSK Investigational Site, Los Angeles, California, 90022, United States|GSK Investigational Site, Los Angeles, California, 90025, United States|GSK Investigational Site, San Diego, California, 92103, United States|GSK Investigational Site, San Dimas, California, 91773, United States|GSK Investigational Site, West Hills, California, 91307, United States|GSK Investigational Site, Lauderdale Lakes, Florida, 33313, United States|GSK Investigational Site, Miami, Florida, 33150, United States|GSK Investigational Site, Pembroke Pines, Florida, 33028, United States|GSK Investigational Site, Macon, Georgia, 31217, United States|GSK Investigational Site, Savannah, Georgia, 31406, United States|GSK Investigational Site, Evergreen 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Kingdom|GSK Investigational Site, Leeds, LS9 7TF, United Kingdom|GSK Investigational Site, London, E1 1BB, United Kingdom|GSK Investigational Site, London, NW3 2QG, United Kingdom|GSK Investigational Site, Manchester, M13 9WL, United Kingdom|GSK Investigational Site, Oxford, OX3 7LE, United Kingdom
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