| Outcome Measures: |
Primary: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites, Serial blood samples were collected from participants at indicated time points for Pharmacokinetic (PK) analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. PK Population comprised of participants in the 'All Subjects' Population for whom a PK sample was obtained and analyzed., Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14|AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites, Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2487818 and GSK2531398). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants., Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1|Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites, Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14 | Secondary: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs), An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth defect, other situations, and is associated with liver injury and impaired liver function. Analysis was performed on All Subjects Population which comprised of all enrolled participants who received at least one dose of study treatment., Up to Day 24|Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels, Blood samples were collected from participants to evaluate clinical chemistry parameters including glucose, calcium, chloride, CO2, potassium, sodium and urea. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Albumin and Protein Levels, Blood samples were collected from participants to evaluate clinical chemistry parameters including albumin and protein. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels, Blood samples were collected from participants to evaluate clinical chemistry parameters including direct bilirubin, bilirubin, creatinine and urate. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels, Blood samples were collected from participants to evaluate clinical chemistry parameters including ALP, AST and GGT. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels, Blood samples were collected from participants to evaluate clinical chemistry parameters including ALT and creatinine kinase. Change from Baseline in clinical chemistry parameters at Day 3, Day 7, Day 11, Day 14 and Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Baseline and Day 3, 7, 11, 14, 17|Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels, Blood samples were collected from participants to evaluate clinical hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. NA indicates data is not available. Mean and standard deviation are presented. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Erythrocyte and Reticulocyte Levels, Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocyte and reticulocyte. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. NA indicates data is not available. Mean and standard deviation are presented. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Hematocrit Levels, Blood samples were collected from participants to evaluate clinical hematology parameters including hematocrit. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Hemoglobin Levels, Blood samples were collected from participants to evaluate clinical hematology parameters including hemoglobin. Change from Baseline in clinical hematology parameters at Day 3, Day 7, Day 11 and Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Baseline and Day 3, 7, 11, 17|Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC), Blood samples were collected from participants to evaluate clinical hematology parameters including MCHC. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Mean Corpuscular Volume (MCV), Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels, Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed., Baseline and Day 17|Number of Participants With Abnormal Electrocardiogram (ECG) Findings, Single measurements of 12-lead ECG were obtained in supine position after at least 10 minutes of rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) interval. Participants with abnormal ECG findings at worst-case observation Carried Forward for triplicate measurements (WOCF) post-Baseline visit are presented. Only participants with data available at WOCF visit were analyzed., Day 17|Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest. Change from Baseline in SBP and DBP at Day 17 and Day 24 (follow-up) are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Baseline, Day 17 and Day 24|Change From Baseline in Pulse Rate, Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest. Change from Baseline in pulse rate at Day 17 and Day 24 (follow-up) are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Baseline, Day 17 and Day 24|Change From Baseline in Body Temperature, Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest. Change from Baseline in body temperature at Day 17 and Day 24 (follow-up) are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Baseline, Day 17 and Day 24|Number of Participants With Abnormal Physical Examination Findings, A complete physical examination was planned to include assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. This analysis was planned but not performed. Any significant finding was captured as an AE., Up to Day 17|Peritoneal Dialysis Clearance of GSK1278863 and Metabolites, Peritoneal dialysate samples for PK analysis of GSK1278863 and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401) were collected. Peritoneal dialysis clearance of GSK1278863 and metabolites was calculated from Day 14 dialysate excretion data as total amount of analyte excreted over 24 hours divided by plasma AUC (0-tau). Geometric mean and geometric coefficient of variation are presented. NA indicates data is not available. Geometric coefficient of variation could not be calculated due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Day 14|Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites, Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403, GSK2531401). Geometric mean and geometric coefficient of variation have been presented for all metabolites. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants, which is indicated by NA. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14|Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites, Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Median and full range have been presented for all metabolites. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14|Accumulation Ratio of GSK1278863 and Metabolites, The observed accumulation ratio was determined to estimate the extent of accumulation for GSK1278863 and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401) after repeat dosing. Accumulation ratio was calculated by using AUC (0-tau) values at Day 1 and Day 14. Analysis was performed using mixed effect model fitted with day (single and repeat dose) as fixed effect and participant as random effect. Mean ratio and 90% confidence intervals have been presented., Day 1 and Day 14|Time Invariance Ratio of GSK1278863 and Metabolites, Time invariance ratio for GSK1278863 and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401) was calculated by analyzing AUC (0-inf) at Day 1 and AUC (0-tau) at Day 14. Analysis was performed using mixed effect model fitted with day (single and repeat dose) as fixed effect and participant as random effect. Mean ratio and 90% confidence intervals have been presented. NA indicates data is not available. Data could not be calculated due to insufficient data., Day 1 and Day 14|Plasma Concentration of Erythropoietin, Serial blood samples were collected from participants at indicated time points to analyze plasma concentration of erythropoietin after repeat-dose administration of GSK1278863. Geometric mean and geometric coefficient of variation have been presented. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11|Plasma Concentration of Hepcidin, Serial blood samples were collected from participants at indicated time points to analyze plasma concentration of hepcidin after repeat-dose administration of GSK1278863. Geometric mean and geometric coefficient of variation have been presented. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles)., Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11
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