| Outcome Measures: |
Primary: Modeled Hgb Change From Baseline Over 4 Weeks of Treatment, Modeled Hgb change from baseline over 4 weeks was derived using a random coefficient mixed effects linear regression model. The model included fixed effects for baseline Hgb, treatment and a treatment by day interaction. Random effects was fitted in the intercept and the slope over time. All data up until investigational product discontinuation was included for Hgb efficacy evaluable participants; where efficacy evaluable was defined as having a baseline and at least 2 on-treatment Hgb assessments. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (average of Week -2, -1 and Day 1) and Week 4 | Secondary: Model-Adjusted Maximum Hgb Changes Over 4 Weeks, Maximum Hgb change over 4 weeks was analyzed using an ANCOVA model with terms included for treatment and baseline Hgb value. Least square mean estimates and 95% CI for each treatment group were reported. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the baseline value from the individual post-dose visit values., Baseline (average of Week -2 , -1 and Day 1 visits) and 4 weeks|Number of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb, Number of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb from baseline were reported. Entry into the study required a target stable Hgb of 8.5-11.0 g/dL. A stable Hgb value was confirmed from three Hgb values taken during the screening period at Week -2, Week -1 and Day 1 (randomization). The average of these three values was used for Baseline Hgb., Up to 4 weeks|Percentage of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb, Percentage of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb from baseline were reported. Entry into the study requires a target stable Hgb of 8.5-11.0 g/dL. A stable Hgb value was confirmed from three Hgb values taken during the screening period at Week -2, Week -1 and Day 1 (randomization). The average of these three values was used for Baseline Hgb., Up to 4 weeks|Number of Participants Who Reached Hgb Stopping Criteria, The Hgb stopping criteria was defined as reaching to value \<8.0 g/dL, \>=8.0 - \<13.0 (\>= 2g/dL absolute Hgb change over 1 week ) or \>=13.0 g/dL. The number of participants who reached the Hgb stopping criteria of Hgb concentration were presented., Up to Week 4|Change From Baseline in Hepcidin at Week 2 and Week 4, Blood samples for hepcidin were collected at Day 1 (pre-dose), Week 2 (approximately between 4 to 8 h) and Week 4 (pre-dose). Hepcidin is a regulator of iron metabolism. Baseline was the last pre-dose value on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. Where hepcidin values were missing because the value was below the quantification limit (BQL), the BQL value was imputed., Baseline (Pre-dose on Day 1), Week 2 and 4|Change From Baseline in Ferritin at Week 2 and Week 4, Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in Transferrin at Week 2 and Week 4, Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in Transferrin Saturation at Week 2 and Week 4, Transferrin saturation was measured as a percentage, and is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value for transferrin saturation was the pre-dose value on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in Total Iron Binding Capacity at Week 2 and Week 4, Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in Total Iron at Week 2 and Week 4, Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Week 2 and Week 4, Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in Hematocrit and Reticulocytes Over 4 Weeks, Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 pre-dose), Week 1, 2, 3, and 4|Change From Baseline in Erythropoietin at Week 2 and Week 4, Blood samples for erythropoietin were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1 and 3 h after this fist sample) and Week 4 (Pre-dose and 3 h post-dose). The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 Pre-dose), Week 2 and 4|Change From Baseline in Red Blood Cells Count Over 4 Weeks, Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values., Baseline (Day 1 pre-dose), week 1, 2, 3, 4|Change From Baseline in Vascular Endothelial Growth Factor (VEGF) at Week 2 and Week 4, Blood samples for VEGF were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1 and 3 h after this fist sample) and Week 4 (Pre-dose and 3 h post-dose). Baseline was the Day 1 pre-dose value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values., Baseline (Pre-dose), week 2 and 4|Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition., Up to 6 weeks|Number of Participants Discontinuing the Study Treatment Due to AEs, AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. number of participants discontinuing the study treatment due to AEs., Up to 6 weeks|Absolute Values of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK) at Baseline (Day 1), Week 2, 4, and 6, Clinical chemistry parameters including ALT, ALP, AST, CK were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 2, 4, and 6|Absolute Values of Albumin, Apolipoprotein A1, Apolipoprotein Total, Total Protein at Baseline (Day 1), Week 2, 4, and 6, Clinical chemistry parameters including albumin, apolipoprotein A1, apolipoprotein total, total protein were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 2, 4, and 6|Absolute Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Baseline (Day 1), Week 2, 4, and 6, Clinical chemistry parameters including calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 2, 4, and 6|Absolute Values of Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin at Baseline (Day 1), Week 2, 4, and 6, Clinical chemistry parameters including creatinine, direct bilirubin, indirect bilirubin, total bilirubin were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 2, 4, and 6|Absolute Values of Urine Total Protein/Creatinine Ratio at Baseline (Day 1), Week 2, 4, and 6, Absolute values of urine total protein/creatinine ratio at Baseline (Day 1), Week 2, 4, and follow-up (week 6) were reported., Baseline (Day 1), Week 2, 4, and 6|Change From Baseline Values of ALT, ALP, AST, CK at Week 2, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the Baseline value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. Change from Baseline values of ALT, AST, ALP and CK at Week 2, 4, and 6, Baseline (Day 1), Week 2, 4, and 6|Change From Baseline Values of Albumin, Apolipoprotein A1, Apolipoprotein Total, Total Protein at Week 2, 4, and 6, Baseline values were recorded on Day 1 (Pre dose). If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of albumin, apolipoprotein A1, apolipoprotein total, total protein at Week 2, 4, and 6 were reported., Baseline (Day 1), Week 2, 4, and 6|Change From Baseline Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Week 2, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium at Week 2, 4, and 6 were reported., Baseline (Day 1), Week 2, 4, and 6|Change From Baseline Values of Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin at Week 2, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of creatinine, direct bilirubin, indirect bilirubin, total bilirubin at Week 2, 4, and 6 were reported., Baseline (Day 1), Week 2, 4, and 6|Change From Baseline Values of Urine Total Protein/Creatinine Ratio at Week 2, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of urine total protein/creatinine ratio at Week 2, 4, and 6 were reported., Baseline (Day 1), Week 2, 4, and 6|Absolute Values of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count (Absolute) at Baseline, Week 1, 2, 3, 4, and 6, Hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet count, WBC count (absolute) were assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Absolute Values of Mean Corpuscle Volume at Baseline, Week 1, 2, 3, 4 and 6, Hematology parameter mean corpuscle volume was assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Absolute Values of Mean Corpuscle Hgb Concentration at Baseline (Day 1), Week 1, 2, 3, 4, and 6, Hematology parameter Mean Corpuscle Hgb Concentration was assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Absolute Values of Reticulocyte Count at Baseline (Day 1), Week 1, 2, 3, 4, and 6, Hematology parameter reticulocyte were assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6)., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, WBC Count (Absolute) at Week 1, 2, 3, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet count, WBC count (absolute) at Week 1, 2, 3, 4, and 6 were reported., Baseline (Day 1), Week 1, 2, 3, 4, and 6|Change From Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6 were reported., Baseline (Day 1), Week 1, 2, 3, 4, and 6|Change From Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6, Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6 were reported., Baseline (Day 1), Week 1, 2, 3, 4, and 6|Absolute Values of Systolic Blood Pressure and Diastolic Blood Pressure Baseline, Week 1, Week 2, Week 3, Week 4 and Week 6, Absolute values of systolic blood pressure and diastolic blood pressure Baseline (Day 1), Week 1, 2, 3, 4, and 6 as vital parameters were reported. Three measurements of systolic blood pressure and diastolic blood pressure were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff)., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 1, 2, 3, 4, and 6, Three measurements of SBP and DBP were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in systolic blood pressure and diastolic blood pressure at Week 1, 2, 3, 4, and 6 were reported., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Absolute Values of Heart Rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6, Absolute values of heart rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6 were reported as vital parameter. Three measurements of heart rate were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff)., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Change From Baseline in Heart Rate at Week 1, 2, 3, 4, and 6, Three measurements of heart rate were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. change from baseline in heart rate at Week 1, 2, 3, 4, and 6 were reported., Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6|Absolute Electrocardiogram (ECG) Parameter Values at Baseline (Screening), Week 2, 4, and 6, Full 12-lead ECGs were recorded in participants who were rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. Full 12-lead ECGs were recorded on the provided ECG machine that automatically calculates heart rate, PR, QRS, QT and QTc intervals. Absolute ECG parameters including PR interval, QT interval and QRS duration values at Baseline (Screening), Week 2, 4, and 6 were reported., Baseline (Screening), Week 2, 4, and 6|Change From Baseline in ECG Parameters at Week 2, 4 and 6, Full 12-lead ECGs were recorded in participants who were rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. Full 12-lead ECGs were recorded on the provided ECG machine that automatically calculates heart rate, PR, QRS, QT and QTc intervals. Baseline ECG values were defined as measurements taken at screening. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values., Baseline (Screening), Week 2, 4, and 6|Mean Maximum Plasma Concentration (Cmax) of GSK1278863 and GSK1278863 Metabolites, Cmax of GSK1278863 and GSK1278863 metabolites (M1, M2, M3, M4, M5 and M6) were reported. For assessment of Pharmacokinetics parameters blood samples were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose)., Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose).|Mean Steady State Area Under the Curve (AUC) of GSK1278863 and GSK1278863 Metabolites, Mean Steady state AUC of GSK1278863 and GSK1278863 metabolites (M1, M2, M3, M4, M5 and M6) were reported. For pharmacokinetic parameter assessment blood samples were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this fist sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose)., Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose)
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| Locations: |
GSK Investigational Site, Azusa, California, 91702, United States|GSK Investigational Site, Bakersfield, California, 93309, United States|GSK Investigational Site, Chino, California, 91710, United States|GSK Investigational Site, Los Angeles, California, 90022, United States|GSK Investigational Site, Los Angeles, California, 90025, United States|GSK Investigational Site, Los Angeles, California, 90057, United States|GSK Investigational Site, North Hollywood, California, 91606-1559, United States|GSK Investigational Site, Orange, California, 92868, United States|GSK Investigational Site, Riverside, California, 92505, United States|GSK Investigational Site, San Dimas, California, 91773, United States|GSK Investigational Site, West Hills, California, 91307, United States|GSK Investigational Site, Yuba City, California, United States|GSK Investigational Site, Denver, Colorado, 80230, United States|GSK Investigational Site, Daytona Beach, Florida, 32117, United States|GSK Investigational Site, Edgewater, Florida, 32132, United States|GSK Investigational Site, Fort Lauderdale, Florida, 33308, United States|GSK Investigational Site, Jacksonville, Florida, 32258, United States|GSK Investigational Site, Miami, Florida, 33145, United States|GSK Investigational Site, Miami, Florida, 33150, United States|GSK Investigational Site, Miami, Florida, 33173, United States|GSK Investigational Site, Ocala, Florida, 34471, United States|GSK Investigational Site, Pembroke Pines, Florida, 33028, United States|GSK Investigational Site, Port Charlotte, Florida, 33952, United States|GSK Investigational Site, Savannah, Georgia, 31406, United States|GSK Investigational Site, Evanston, Illinois, 60201, United States|GSK Investigational Site, Gurnee, Illinois, 60031, United States|GSK Investigational Site, Detroit, Michigan, 48236, United States|GSK Investigational Site, Asheville, North Carolina, 28801, United States|GSK Investigational Site, Charlotte, North Carolina, United States|GSK Investigational Site, Wilmington, North Carolina, 28401, United States|GSK Investigational Site, Winston-Salem, North Carolina, 27103, United States|GSK Investigational Site, Columbus, Ohio, 43210, United States|GSK Investigational Site, Oklahoma City, Oklahoma, 73116, United States|GSK Investigational Site, Portland, Oregon, 97210, United States|GSK Investigational Site, Bethlehem, Pennsylvania, 18017, United States|GSK Investigational Site, Erie, Pennsylvania, 16507, United States|GSK Investigational Site, Uniontown, Pennsylvania, 15401, United States|GSK Investigational Site, Arlington, Texas, 76011, United States|GSK Investigational Site, Austin, Texas, 78751, United States|GSK Investigational Site, Corsicana, Texas, 75110, United States|GSK Investigational Site, Greenville, Texas, 75402, United States|GSK Investigational Site, Houston, Texas, 77054, United States|GSK Investigational Site, Houston, Texas, 77099, United States|GSK Investigational Site, San Antonio, Texas, 78229, United States|GSK Investigational Site, Temple, Texas, 76502, United States|GSK Investigational Site, Silverdale, Washington, 98383, United States|GSK Investigational Site, Calgary, Alberta, T2R 0X7, Canada|GSK Investigational Site, Brampton, Ontario, L6T 0G1, Canada|GSK Investigational Site, London, Ontario, N6A 5A5, Canada|GSK Investigational Site, Sudbury, Ontario, P3E 5J1, Canada|GSK Investigational Site, Heidelberg, Baden-Wuerttemberg, 69120, Germany|GSK Investigational Site, Aschaffenburg, Bayern, 63741, Germany|GSK Investigational Site, Demmin, Mecklenburg-Vorpommern, 17109, Germany|GSK Investigational Site, Lehrte, Niedersachsen, 31275, Germany|GSK Investigational Site, Hamburg, 22297, Germany
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