Anaemia
Conditions
Keywords
pharmacokinetics, Chronic kidney disease, peritoneal dialysis, hemoglobin, Anemia, GSK1278863, Prolyl hydroxylase inhibitor, erythropoiesis stimulating agents
Brief summary
GSK1278863 is an orally-active, novel small molecule agent which inhibits hypoxia-inducible factor (HIF) prolyl -4- hydroxylases (PHDs) and is in development for the treatment of anaemia associated with chronic kidney disease (CKD). As the kidney represents a major site of elimination for many drugs and their metabolites, and GSK1278863 will be administered to subjects with various stages of renal disease, it is important to characterize the pharmacokinetics in this target patient population. The purpose of this study is to characterize the pharmacokinetics of GSK1278863 and its metabolites in subjects with end stage renal disease (ESRD) undergoing peritoneal dialysis. This will be a repeat-dose, open-label, parallel-group study. Approximately 30 subjects with ESRD will be enrolled in two cohorts (15 subjects in each cohort) to ensure that 6 subjects on continuous ambulatory peritoneal dialysis (CAPD) (cohort 1) and 6 subjects on automated peritoneal dialysis APD (cohort 2) complete dosing and critical assessments. GSK1278863 will be administered once daily for 14 days. Primary pharmacokinetic assessments will be made on Days 1 and 14.
Interventions
DRUGGSK1278863
Round, biconvex, white film coated tablet containing 5 mg GSK1278863.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
SAFETY: * Satisfactory medical evaluation based upon medical history, medication history, physical examination, and clinical laboratory data obtained at the Screening visit. The determination of clinical significance will be made by the Investigator and the GlaxoSmithKline (GSK) Medical Monitor and will require that the finding is unlikely to introduce additional risk factors or interfere with the study procedures, or the integrity of the study. * Corrected QT interval (QTc) \<470 milliseconds (msec) OR QTc \<480 msec in subjects with Bundle Branch Block. These should be based on average of triplicate values obtained over a brief recording period at Screening and on Day -1 and the single reading on Day 17. The same QT correction formula should be used to determine inclusion and discontinuation for any individual subject throughout the study. * Vitamin B12 and folate above the lower limit of normal at Screening. * Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and bilirubin \<=1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). EFFICACY: * A subject is eligible to enroll and participate in this study if he/she has ESRD and is on peritoneal dialysis for at least 2 months with an average urine output of \<750 mL/daily with a combined weekly (urine and peritoneal dialysis output) Kt/V urea \>1.7 measured at any time within last 3 months. * No history of peritoneal dialysis-associated peritonitis, peritoneal catheter tunnel (exit site) infection or leakage for at least 3 months before study. * Meets the following erythropoiesis stimulating agent (ESA) criteria: Is ESA naive (i.e., no ESA use within the previous 12 weeks of screening) OR agrees to discontinue ESA (if currently using ESA) for at least 7 days prior to first dose of GSK1278863 until completion of Follow-up visit (If the subject has a scheduled ESA interval which is \<=7 days, ESA treatment must be discontinued for at least 7 days prior to first dose of GSK1278863. If the subject has a scheduled ESA interval which is \>7 days, ESA treatment must be discontinued for at least the scheduled interval length \[e.g., if ESA interval is 14 days, then ESA must be discontinued for \>=14 days\] prior to the first dose of GSK1278863) * Has a haemoglobin value: For ESA naïve subjects: \<10.0 g/dL (UK site(s) only: \<=11.0 g/dL); For subjects receiving ongoing ESA treatment: \<=11.0 g/dL at Screening (UK site(s) only: \<=12.0 g/dL at Screening). OTHER: * Subjects who are \>=18 years of age at the time of Screening. * A female subject is eligible to participate if she is of: (a) Childbearing potential, and agrees to use one of the contraception methods described in the protocol. This criterion must be followed from the time of Screening until completion of the Follow-up Visit; (b) Non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 international units (IU)/litre (L) and estradiol \<=10 picograms (pg)/mL (or \<=37 picomoles \[pmol\]/L) is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods described in the protocol 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. For most forms of HRT, at least 2 months must elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. * Body weight \>45 kilograms (kg) and \<140 kg at Screening. * The subject is mentally and legally able to comply with the requirements and restrictions of the protocol and has provided signed informed consent prior to participation in any protocol-specific procedures, including Screening procedures.
Exclusion criteria
SAFETY * A positive test for Human Immunodeficiency Virus (HIV) antibody. * Uncontrolled hypertension (diastolic blood pressure \[BP\] \>100 millimetres of mercury \[mmHg\] or systolic BP \>170 mmHg) at Screening. * History of drug abuse or dependence within 6 months of the study. * History of sensitivity to GSK1278863, or its components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation. * History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency). * History of thrombosis defined as deep vein thrombosis, stroke, pulmonary embolism or other thrombosis related condition within 3 months prior to Screening. * History of myocardial infarction or acute coronary syndrome within 3 months prior to Screening. * History of stroke or transient ischaemic attack within 3 months prior to Screening. * Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of GSK1278863. Examples of conditions that could interfere with normal gastrointestinal anatomy or motility include gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue. Examples of conditions that could interfere with hepatic function include Gilbert's syndrome. * Evidence of active peptic, duodenal or esophageal ulcer disease at Screening OR history of clinically significant gastro-intestinal (GI) bleeding within 3 months prior to Screening. * Subjects with chronic inflammatory disease that could impact erythropoiesis (e.g. scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease). * Subjects with a history of symptomatic right heart failure. * Subjects with Class III or Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system. * Active malignancy or diagnosis of malignancy within 5 years prior to Screening (excluding successfully treated basal or squamous cell carcinoma). * History of proliferative vascular eye disease (e.g., choroidal or retinal disease, such as neovascular age-related macular degeneration, proliferative diabetic retinopathy or macular edema) based upon having had an ophthalmologic exam within 12 months prior to the end of the Screening period (The screening period is from the screening visit until Day -1). * Pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test at Screening or Day -1. * Lactating females. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period prior to first dose. * Consumption of red wine, grapefruit (juice), blood orange (juice), star fruit, onions, kale, broccoli, green beans, or apples from 7 days prior to the first dose of investigational product until the Follow-up visit, unless in the opinion of the Investigator and GSK Medical Monitor this will not interfere with the study procedures and compromise subject safety. * Use or planned use of any prescription or non-prescription drugs that are prohibited within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of GSK1278863 until completion of the follow-up visit, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. * The following medications are specifically prohibited for the duration of the study (from Screening to the follow-up visit at the end of the study): Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) with the exception of low dose (\<=325 mg/day) aspirin/acetylsalicylic acid. Occasional NSAID use is permitted; Immunosuppressant drugs and drugs used to treat malignancies (including corticosteroids at doses \>10 mg prednisolone per day or equivalent) within 2 weeks of first dose of GSK1278863. Note: Failed transplant subjects back on peritoneal dialysis are eligible for participating in this study but should not be on immunosuppressive medications within 3 months prior to Screening. * The subject has participated in a clinical trial and has received an experimental investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). EFFICACY: * The values of ferritin and transferrin within 3 months prior to Screening are: (a) transferrin saturation \<20%; (b) serum ferritin \<100 micrograms (mcg)/L OTHER: * A positive pre-dosing drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. A positive pre-dosing screen for medications that are prescribed to a renal subject for pre-existing condition(s), may be allowed if in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. * History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. * History of regular use within 6 months of the study of tobacco- or nicotine-containing products in excess of 20 cigarettes per day or equivalent. * Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the informed consent and as directed by site staff. * Subject is either an immediate family member of a participating Investigator, study coordinator, employee of an Investigator; or is a member of the staff conducting the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | 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 | 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. |
| AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1 | 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. |
| Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Baseline and Day 17 | 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. |
| Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | Baseline and Day 17 | 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. |
| Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Baseline and Day 3, 7, 11, 14, 17 | 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). |
| Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Baseline and Day 17 | 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. |
| Change From Baseline in Erythrocyte and Reticulocyte Levels | Baseline and Day 17 | 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. |
| Change From Baseline in Hematocrit Levels | Baseline and Day 17 | 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. |
| Change From Baseline in Hemoglobin Levels | Baseline and Day 3, 7, 11, 17 | 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). |
| Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) | Baseline and Day 17 | 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. |
| Change From Baseline in Mean Corpuscular Volume (MCV) | Baseline and Day 17 | 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. |
| Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels | Baseline and Day 17 | 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. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Day 17 | 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. |
| Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Up to Day 24 | 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. |
| Change From Baseline in Pulse Rate | Baseline, Day 17 and Day 24 | 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). |
| Change From Baseline in Body Temperature | Baseline, Day 17 and Day 24 | 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). |
| Number of Participants With Abnormal Physical Examination Findings | Up to Day 17 | 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. |
| Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | Day 14 | 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). |
| Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | 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 | 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). |
| Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | 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 | 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). |
| Accumulation Ratio of GSK1278863 and Metabolites | Day 1 and Day 14 | 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. |
| Time Invariance Ratio of GSK1278863 and Metabolites | Day 1 and Day 14 | 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. |
| Plasma Concentration of Erythropoietin | Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11 | 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). |
| Plasma Concentration of Hepcidin | Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11 | 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). |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline, Day 17 and Day 24 | 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). |
| Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Baseline and Day 17 | 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. |
| Change From Baseline in Albumin and Protein Levels | Baseline and Day 17 | 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. |
Countries
United States
Participant flow
Recruitment details
This repeat-dose, pharmacokinetic (PK) study of GSK1278863 was conducted at two centers in the United States (US). Participants with End Stage Renal Disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) were included in this study.
Pre-assignment details
A total of 20 participants with ESRD were screened; of which 12 were screen failures and 8 entered the study to receive 5 milligrams (mg) of GSK1278863 once daily for 14 days.
Participants by arm
| Arm | Count |
|---|---|
| Participants Undergoing CAPD Participants on CAPD received 1 tablet (5 mg) of GSK1278863 by oral route once daily with half glass of water for 14 days. On Day 1 and Day14, the dose was administered within 30 minutes after completion of night CAPD treatment or morning last fill of peritoneal dialysis fluid; on any other study days, the dose was administered within 2 hours after completion of night CAPD treatment or morning last fill of peritoneal dialysis fluid. | 1 |
| Participants Undergoing APD Participants on APD received 1 tablet (5 mg) of GSK1278863 by oral route once daily with half glass of water for 14 days. On Day 1 and Day14, the dose was administered within 30 minutes after completion of night APD treatment or morning last fill of peritoneal dialysis fluid; on any other study days, the dose was administered within 2 hours after completion of night APD treatment or morning last fill of peritoneal dialysis fluid. | 7 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Other: Reached stopping criteria | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Participants Undergoing CAPD | Participants Undergoing APD | Total |
|---|---|---|---|
| Age, Continuous | 44.0 Years | 57.4 Years STANDARD_DEVIATION 12.01 | 55.8 Years STANDARD_DEVIATION 12.09 |
| Race/Ethnicity, Customized Race customized American Indian or Alaska Native Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race customized Black or African American Heritage | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race customized White- White/Caucasian/European Heritage | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 7 |
| other Total, other adverse events | 1 / 1 | 5 / 7 |
| serious Total, serious adverse events | 0 / 1 | 0 / 7 |
Outcome results
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.
Time frame: 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
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK1278863; Day 1; n=1, 7 | 184.9863 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK1278863; Day 14; n=1, 4 | 162.9366 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2391220; Day 1; n=1, 7 | 245.8999 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2391220; Day 14; n=1, 4 | 258.1199 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2487818; Day 1; n=1, 7 | 116.2608 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2487818; Day 14; n=1, 4 | 114.1857 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2506102; Day 1; n=1,6 | 59.0619 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2506102; Day 14; n=1, 4 | 82.9794 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531398; Day 1; n=1, 7 | 97.0339 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531398; Day 14; n=1, 4 | 97.6587 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531403; Day 1; n=1, 7 | 291.3067 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531403; Day 14; n=1, 4 | 360.2268 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531401; Day 1; n=1, 6 | 173.5919 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531401; Day 14; n=1, 4 | 242.0514 Hour into nanograms per milliliter | — |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531403; Day 1; n=1, 7 | 170.4958 Hour into nanograms per milliliter | Geometric Coefficient of Variation 45.5 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK1278863; Day 1; n=1, 7 | 138.6511 Hour into nanograms per milliliter | Geometric Coefficient of Variation 93.5 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2506102; Day 14; n=1, 4 | 65.2188 Hour into nanograms per milliliter | Geometric Coefficient of Variation 63 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK1278863; Day 14; n=1, 4 | 131.2826 Hour into nanograms per milliliter | Geometric Coefficient of Variation 78.8 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531401; Day 1; n=1, 6 | 104.2971 Hour into nanograms per milliliter | Geometric Coefficient of Variation 48.6 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2391220; Day 1; n=1, 7 | 147.8039 Hour into nanograms per milliliter | Geometric Coefficient of Variation 47.7 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531398; Day 1; n=1, 7 | 63.0979 Hour into nanograms per milliliter | Geometric Coefficient of Variation 45.5 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2391220; Day 14; n=1, 4 | 162.0324 Hour into nanograms per milliliter | Geometric Coefficient of Variation 50.7 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531403; Day 14; n=1, 4 | 228.6081 Hour into nanograms per milliliter | Geometric Coefficient of Variation 69.4 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2487818; Day 1; n=1, 7 | 67.4130 Hour into nanograms per milliliter | Geometric Coefficient of Variation 39.1 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531398; Day 14; n=1, 4 | 65.9664 Hour into nanograms per milliliter | Geometric Coefficient of Variation 53.5 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2487818; Day 14; n=1, 4 | 59.6501 Hour into nanograms per milliliter | Geometric Coefficient of Variation 51.5 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2531401; Day 14; n=1, 4 | 205.7281 Hour into nanograms per milliliter | Geometric Coefficient of Variation 20.1 |
| Participants Undergoing APD | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites | GSK2506102; Day 1; n=1,6 | 44.8180 Hour into nanograms per milliliter | Geometric Coefficient of Variation 37.8 |
Primary
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.
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | GSK1278863 | 184.9888 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | GSK2487818 | 117.2111 Hour into nanograms per milliliter | — |
| Participants Undergoing CAPD | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | GSK2531398 | 104.5268 Hour into nanograms per milliliter | — |
| Participants Undergoing APD | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | GSK1278863 | 138.6860 Hour into nanograms per milliliter | Geometric Coefficient of Variation 93.6 |
| Participants Undergoing APD | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | GSK2487818 | 68.5089 Hour into nanograms per milliliter | Geometric Coefficient of Variation 39.9 |
| Participants Undergoing APD | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites | GSK2531398 | 73.9865 Hour into nanograms per milliliter | Geometric Coefficient of Variation 51.3 |
Primary
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).
Time frame: 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
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK1278863; Day 1; n= 1, 7 | 90.400 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK1278863; Day 14; n= 1, 4 | 57.800 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2391220; Day 1; n= 1, 7 | 19.900 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2391220; Day 14; n= 1, 4 | 20.500 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2487818; Day 1; n= 1, 7 | 19.400 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2487818; Day 14; n= 1, 4 | 18.400 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2506102; Day 1; n= 1, 7 | 3.820 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2506102; Day 14; n= 1, 4 | 5.050 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531398; Day 1; n= 1, 7 | 9.300 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531398; Day 14; n= 1, 4 | 9.220 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531403; Day 1; n= 1, 7 | 18.600 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531403; Day 14; n= 1, 4 | 23.400 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531401; Day 1; n= 1, 7 | 9.920 Nanograms per milliliter | — |
| Participants Undergoing CAPD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531401; Day 14; n= 1, 4 | 13.300 Nanograms per milliliter | — |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531403; Day 1; n= 1, 7 | 11.186 Nanograms per milliliter | Geometric Coefficient of Variation 36.7 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK1278863; Day 1; n= 1, 7 | 58.771 Nanograms per milliliter | Geometric Coefficient of Variation 96.7 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2506102; Day 14; n= 1, 4 | 3.590 Nanograms per milliliter | Geometric Coefficient of Variation 46.5 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK1278863; Day 14; n= 1, 4 | 30.303 Nanograms per milliliter | Geometric Coefficient of Variation 104.4 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531401; Day 1; n= 1, 7 | 4.715 Nanograms per milliliter | Geometric Coefficient of Variation 78.4 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2391220; Day 1; n= 1, 7 | 11.360 Nanograms per milliliter | Geometric Coefficient of Variation 44.3 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531398; Day 1; n= 1, 7 | 5.370 Nanograms per milliliter | Geometric Coefficient of Variation 44.2 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2391220; Day 14; n= 1, 4 | 10.966 Nanograms per milliliter | Geometric Coefficient of Variation 33.1 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531403; Day 14; n= 1, 4 | 13.267 Nanograms per milliliter | Geometric Coefficient of Variation 48.2 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2487818; Day 1; n= 1, 7 | 10.117 Nanograms per milliliter | Geometric Coefficient of Variation 25.7 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531398; Day 14; n= 1, 4 | 4.857 Nanograms per milliliter | Geometric Coefficient of Variation 35.6 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2487818; Day 14; n= 1, 4 | 7.262 Nanograms per milliliter | Geometric Coefficient of Variation 40.4 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2531401; Day 14; n= 1, 4 | 10.404 Nanograms per milliliter | Geometric Coefficient of Variation 17.4 |
| Participants Undergoing APD | Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites | GSK2506102; Day 1; n= 1, 7 | 2.553 Nanograms per milliliter | Geometric Coefficient of Variation 42.7 |
Secondary
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.
Time frame: Day 1 and Day 14
Population: PK Population. CAPD and APD arms were combined to present data for All participants analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK1278863 | 0.896 Ratio of AUC |
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK2391220 | 1.176 Ratio of AUC |
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK2487818 | 1.019 Ratio of AUC |
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK2506102 | 1.581 Ratio of AUC |
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK2531398 | 1.116 Ratio of AUC |
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK2531403 | 1.415 Ratio of AUC |
| Participants Undergoing CAPD | Accumulation Ratio of GSK1278863 and Metabolites | GSK2531401 | 1.948 Ratio of AUC |
Secondary
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).
Time frame: Baseline and Day 3, 7, 11, 14, 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 3; n= 1, 6 | -3.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 7; n= 1, 4 | -7.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 11; 1, 4 | -9.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 14; n= 1, 4 | -7.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 17; n= 1, 4 | -7.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 3; n= 1, 6 | -12.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 7; n= 1, 4 | -12.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 11; n= 1, 4 | 1.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 14; n= 1, 4 | 9.0 IU/L | — |
| Participants Undergoing CAPD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 17; n= 1, 4 | -2.0 IU/L | — |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 11; n= 1, 4 | -135.8 IU/L | Standard Deviation 273.85 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 3; n= 1, 6 | -0.7 IU/L | Standard Deviation 3.98 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 3; n= 1, 6 | -99.7 IU/L | Standard Deviation 161.17 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 7; n= 1, 4 | -2.5 IU/L | Standard Deviation 5.32 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 17; n= 1, 4 | -201.5 IU/L | Standard Deviation 191.83 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 11; 1, 4 | -3.5 IU/L | Standard Deviation 5.8 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 7; n= 1, 4 | -137.8 IU/L | Standard Deviation 230.33 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 14; n= 1, 4 | -0.8 IU/L | Standard Deviation 3.86 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | Creatine kinase; Day 14; n= 1, 4 | -183.5 IU/L | Standard Deviation 247.13 |
| Participants Undergoing APD | Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels | ALT; Day 17; n= 1, 4 | -1.0 IU/L | Standard Deviation 6.06 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Albumin and Protein Levels | Albumin | 3.0 Gram per liter (g/L) | — |
| Participants Undergoing CAPD | Change From Baseline in Albumin and Protein Levels | Protein | 5.0 Gram per liter (g/L) | — |
| Participants Undergoing APD | Change From Baseline in Albumin and Protein Levels | Albumin | -1.3 Gram per liter (g/L) | Standard Deviation 3.2 |
| Participants Undergoing APD | Change From Baseline in Albumin and Protein Levels | Protein | -2.0 Gram per liter (g/L) | Standard Deviation 5.48 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | ALP | 5.0 International unit per liter (IU/L) | — |
| Participants Undergoing CAPD | Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | AST | -1.0 International unit per liter (IU/L) | — |
| Participants Undergoing CAPD | Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | GGT | 0.0 International unit per liter (IU/L) | — |
| Participants Undergoing APD | Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | ALP | -0.5 International unit per liter (IU/L) | Standard Deviation 16.52 |
| Participants Undergoing APD | Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | AST | -3.3 International unit per liter (IU/L) | Standard Deviation 3.77 |
| Participants Undergoing APD | Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels | GGT | -6.3 International unit per liter (IU/L) | Standard Deviation 8.77 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Lymphocytes | 0.260 10^9 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Neutrophils | 1.350 10^9 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Eosinophils | -0.010 10^9 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Platelets | 42.0 10^9 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Monocytes | 0.230 10^9 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Leukocytes | 1.80 10^9 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Basophils | -0.020 10^9 cells/liter | — |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Leukocytes | -0.35 10^9 cells/liter | Standard Deviation 1.008 |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Basophils | 0.010 10^9 cells/liter | Standard Deviation 0.02 |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Eosinophils | 0.060 10^9 cells/liter | Standard Deviation 0.0804 |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Lymphocytes | -0.138 10^9 cells/liter | Standard Deviation 0.3974 |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Monocytes | 0.060 10^9 cells/liter | Standard Deviation 0.3389 |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Neutrophils | -0.365 10^9 cells/liter | Standard Deviation 1.1957 |
| Participants Undergoing APD | Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels | Platelets | -21.0 10^9 cells/liter | Standard Deviation 35.92 |
Secondary
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).
Time frame: Baseline, Day 17 and Day 24
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Body Temperature | Day 17; n= 1, 5 | -0.10 Degree celsius | — |
| Participants Undergoing CAPD | Change From Baseline in Body Temperature | Follow-up; n= 1, 7 | -0.90 Degree celsius | — |
| Participants Undergoing APD | Change From Baseline in Body Temperature | Day 17; n= 1, 5 | -0.20 Degree celsius | Standard Deviation 0.648 |
| Participants Undergoing APD | Change From Baseline in Body Temperature | Follow-up; n= 1, 7 | -0.30 Degree celsius | Standard Deviation 0.548 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Direct bilirubin | 0.0 Micromoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Bilirubin | -2.0 Micromoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Creatinine | 13.30 Micromoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Urate | -30.0 Micromoles per liter | — |
| Participants Undergoing APD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Urate | -25.0 Micromoles per liter | Standard Deviation 87.37 |
| Participants Undergoing APD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Direct bilirubin | -0.5 Micromoles per liter | Standard Deviation 1.91 |
| Participants Undergoing APD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Creatinine | -119.12 Micromoles per liter | Standard Deviation 312.679 |
| Participants Undergoing APD | Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels | Bilirubin | 0.5 Micromoles per liter | Standard Deviation 1 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Erythrocyte and Reticulocyte Levels | Erythrocytes | 0.00 10^12 cells/liter | — |
| Participants Undergoing CAPD | Change From Baseline in Erythrocyte and Reticulocyte Levels | Reticulocytes | 0.02840 10^12 cells/liter | — |
| Participants Undergoing APD | Change From Baseline in Erythrocyte and Reticulocyte Levels | Erythrocytes | -0.05 10^12 cells/liter | Standard Deviation 0.412 |
| Participants Undergoing APD | Change From Baseline in Erythrocyte and Reticulocyte Levels | Reticulocytes | -0.00165 10^12 cells/liter | Standard Deviation 0.044431 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Chloride | -2.0 Millimoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Potassium | 0.20 Millimoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Calcium | 0.360 Millimoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Sodium | 2.0 Millimoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | CO2 | 0.0 Millimoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Urea | 12.50 Millimoles per liter | — |
| Participants Undergoing CAPD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Glucose | -0.10 Millimoles per liter | — |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Urea | -0.38 Millimoles per liter | Standard Deviation 3.568 |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Glucose | 0.27 Millimoles per liter | Standard Deviation 7.191 |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Calcium | 0.040 Millimoles per liter | Standard Deviation 0.2026 |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Chloride | -1.3 Millimoles per liter | Standard Deviation 2.99 |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | CO2 | 0.3 Millimoles per liter | Standard Deviation 5.19 |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Potassium | -0.45 Millimoles per liter | Standard Deviation 0.58 |
| Participants Undergoing APD | Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels | Sodium | -1.5 Millimoles per liter | Standard Deviation 3.7 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Hematocrit Levels | 0.0070 Proportion of red blood cells in blood | — |
| Participants Undergoing APD | Change From Baseline in Hematocrit Levels | -0.0100 Proportion of red blood cells in blood | Standard Deviation 0.0388 |
Secondary
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).
Time frame: Baseline and Day 3, 7, 11, 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Hemoglobin Levels | Day 3; n= 1, 7 | 7.0 g/L | — |
| Participants Undergoing CAPD | Change From Baseline in Hemoglobin Levels | Day 7; n= 1, 5 | 4.0 g/L | — |
| Participants Undergoing CAPD | Change From Baseline in Hemoglobin Levels | Day 11; n= 1, 5 | 0.0 g/L | — |
| Participants Undergoing CAPD | Change From Baseline in Hemoglobin Levels | Day 17; n= 1, 4 | 5.0 g/L | — |
| Participants Undergoing APD | Change From Baseline in Hemoglobin Levels | Day 17; n= 1, 4 | -1.3 g/L | Standard Deviation 13.74 |
| Participants Undergoing APD | Change From Baseline in Hemoglobin Levels | Day 3; n= 1, 7 | 3.1 g/L | Standard Deviation 11.96 |
| Participants Undergoing APD | Change From Baseline in Hemoglobin Levels | Day 11; n= 1, 5 | -3.2 g/L | Standard Deviation 8.14 |
| Participants Undergoing APD | Change From Baseline in Hemoglobin Levels | Day 7; n= 1, 5 | -2.2 g/L | Standard Deviation 9.78 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) | 8.0 g/L | — |
| Participants Undergoing APD | Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) | 6.3 g/L | Standard Deviation 3.86 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels | 1.00 Picograms | — |
| Participants Undergoing APD | Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels | -0.02 Picograms | Standard Deviation 0.866 |
Secondary
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.
Time frame: Baseline and Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Mean Corpuscular Volume (MCV) | 1.0 Femtoliter | — |
| Participants Undergoing APD | Change From Baseline in Mean Corpuscular Volume (MCV) | -1.5 Femtoliter | Standard Deviation 1.73 |
Secondary
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).
Time frame: Baseline, Day 17 and Day 24
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Pulse Rate | Day 17; n= 1, 5 | -9.0 Beats per minute | — |
| Participants Undergoing CAPD | Change From Baseline in Pulse Rate | Follow-up; n= 1, 7 | -6.0 Beats per minute | — |
| Participants Undergoing APD | Change From Baseline in Pulse Rate | Day 17; n= 1, 5 | -5.6 Beats per minute | Standard Deviation 9.53 |
| Participants Undergoing APD | Change From Baseline in Pulse Rate | Follow-up; n= 1, 7 | -7.0 Beats per minute | Standard Deviation 11.58 |
Secondary
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).
Time frame: Baseline, Day 17 and Day 24
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; Day 17; n= 1, 5 | 12.0 Millimeters of mercury | — |
| Participants Undergoing CAPD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; follow-up; n= 1, 7 | 24.0 Millimeters of mercury | — |
| Participants Undergoing CAPD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; Day 17; n= 1, 5 | 10.0 Millimeters of mercury | — |
| Participants Undergoing CAPD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; follow-up; n= 1, 7 | -4.0 Millimeters of mercury | — |
| Participants Undergoing APD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; follow-up; n= 1, 7 | 0.1 Millimeters of mercury | Standard Deviation 12.52 |
| Participants Undergoing APD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; Day 17; n= 1, 5 | -10.4 Millimeters of mercury | Standard Deviation 10.06 |
| Participants Undergoing APD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP; Day 17; n= 1, 5 | -3.4 Millimeters of mercury | Standard Deviation 13.07 |
| Participants Undergoing APD | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP; follow-up; n= 1, 7 | -10.0 Millimeters of mercury | Standard Deviation 12.46 |
Secondary
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.
Time frame: Day 17
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Undergoing CAPD | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
| Participants Undergoing APD | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 3 Participants |
Secondary
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.
Time frame: Up to Day 17
Population: All Subjects Population
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.
Time frame: Up to Day 24
Population: All subjects Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Undergoing CAPD | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Non-serious AEs | 1 Participants |
| Participants Undergoing CAPD | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 0 Participants |
| Participants Undergoing APD | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Non-serious AEs | 5 Participants |
| Participants Undergoing APD | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 0 Participants |
Secondary
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).
Time frame: Day 14
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2531398; n= 1, 4 | 151.29 Milliliter per hour | — |
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2391220; n= 1, 4 | 154.68 Milliliter per hour | — |
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2531403; n= 1, 4 | 155.75 Milliliter per hour | — |
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2506102; n= 1, 4 | 167.89 Milliliter per hour | — |
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2531401; n= 1, 4 | 201.80 Milliliter per hour | — |
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK1278863; n= 1, 0 | 12.07 Milliliter per hour | — |
| Participants Undergoing CAPD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2487818; n= 1, 3 | 124.40 Milliliter per hour | — |
| Participants Undergoing APD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2531401; n= 1, 4 | 48.89 Milliliter per hour | Geometric Coefficient of Variation 199.7 |
| Participants Undergoing APD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2391220; n= 1, 4 | 31.68 Milliliter per hour | Geometric Coefficient of Variation 165.5 |
| Participants Undergoing APD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2487818; n= 1, 3 | 13.08 Milliliter per hour | Geometric Coefficient of Variation 195.3 |
| Participants Undergoing APD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2506102; n= 1, 4 | 40.05 Milliliter per hour | Geometric Coefficient of Variation 169.7 |
| Participants Undergoing APD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2531398; n= 1, 4 | 28.39 Milliliter per hour | Geometric Coefficient of Variation 177.5 |
| Participants Undergoing APD | Peritoneal Dialysis Clearance of GSK1278863 and Metabolites | GSK2531403; n= 1, 4 | 36.18 Milliliter per hour | Geometric Coefficient of Variation 183.2 |
Secondary
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).
Time frame: Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 1; 8 hours; n= 1, 7 | 23.540 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 11; pre-dose; n= 1, 3 | 8.690 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 1; 24 hours; n= 1, 7 | 13.570 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 14; pre-dose; n= 1, 4 | 9.490 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 1; 4 hours; n= 1, 7 | 11.590 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 14; 4 hours; n= 1, 3 | 12.660 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 3; pre-dose; n= 1, 6 | 10.030 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 14; 8 hours; n= 1, 4 | 30.220 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 1; 12 hours; n= 1, 7 | 32.210 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 14; 12 hours; n= 1, 4 | 21.050 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 7; pre-dose; n= 1, 3 | 5.070 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 14; 24 hours; n= 1, 4 | 6.590 IU/L | — |
| Participants Undergoing CAPD | Plasma Concentration of Erythropoietin | Day 1; pre-dose; n= 1, 7 | 13.860 IU/L | — |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 14; 24 hours; n= 1, 4 | 6.735 IU/L | Geometric Coefficient of Variation 88.1 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 1; pre-dose; n= 1, 7 | 11.363 IU/L | Geometric Coefficient of Variation 124.9 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 1; 4 hours; n= 1, 7 | 14.494 IU/L | Geometric Coefficient of Variation 127.1 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 1; 8 hours; n= 1, 7 | 36.257 IU/L | Geometric Coefficient of Variation 96 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 1; 12 hours; n= 1, 7 | 32.629 IU/L | Geometric Coefficient of Variation 112.4 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 1; 24 hours; n= 1, 7 | 13.005 IU/L | Geometric Coefficient of Variation 127.5 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 3; pre-dose; n= 1, 6 | 15.452 IU/L | Geometric Coefficient of Variation 152.9 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 7; pre-dose; n= 1, 3 | 8.023 IU/L | Geometric Coefficient of Variation 66.4 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 11; pre-dose; n= 1, 3 | 9.466 IU/L | Geometric Coefficient of Variation 69.8 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 14; pre-dose; n= 1, 4 | 6.036 IU/L | Geometric Coefficient of Variation 71.2 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 14; 4 hours; n= 1, 3 | 7.674 IU/L | Geometric Coefficient of Variation 34.9 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 14; 8 hours; n= 1, 4 | 19.313 IU/L | Geometric Coefficient of Variation 81.6 |
| Participants Undergoing APD | Plasma Concentration of Erythropoietin | Day 14; 12 hours; n= 1, 4 | 25.745 IU/L | Geometric Coefficient of Variation 74.6 |
Secondary
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).
Time frame: Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 7; pre-dose; n= 1, 4 | 825.30 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 1; 12 hours; n= 1, 7 | 1318.00 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 11; pre-dose; n= 1, 4 | 852.90 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 1; pre-dose; n= 1, 7 | 1143.00 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 14; pre-dose; n= 1, 4 | 734.30 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 1; 24 hours; n= 1, 7 | 867.20 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 14; 4 hours; n= 1, 4 | 847.90 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 14; 8 hours; n= 1, 4 | 809.90 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 1; 8 hours; n= 1, 7 | 1427.10 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 14; 12 hours; n= 1, 4 | 705.70 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 3; pre-dose; n= 1, 6 | 1021.70 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 14; 24 hours; n= 1, 4 | 801.30 Micrograms per liter | — |
| Participants Undergoing CAPD | Plasma Concentration of Hepcidin | Day 1; 4 hours; n= 1, 7 | 1286.00 Micrograms per liter | — |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 14; 24 hours; n= 1, 4 | 733.66 Micrograms per liter | Geometric Coefficient of Variation 81.9 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 1; pre-dose; n= 1, 7 | 863.21 Micrograms per liter | Geometric Coefficient of Variation 100.3 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 1; 4 hours; n= 1, 7 | 922.86 Micrograms per liter | Geometric Coefficient of Variation 108.3 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 1; 8 hours; n= 1, 7 | 760.14 Micrograms per liter | Geometric Coefficient of Variation 80.1 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 1; 12 hours; n= 1, 7 | 812.62 Micrograms per liter | Geometric Coefficient of Variation 86.1 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 1; 24 hours; n= 1, 7 | 802.06 Micrograms per liter | Geometric Coefficient of Variation 93.5 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 3; pre-dose; n= 1, 6 | 819.17 Micrograms per liter | Geometric Coefficient of Variation 90.7 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 7; pre-dose; n= 1, 4 | 839.42 Micrograms per liter | Geometric Coefficient of Variation 81.5 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 11; pre-dose; n= 1, 4 | 800.77 Micrograms per liter | Geometric Coefficient of Variation 91.3 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 14; pre-dose; n= 1, 4 | 768.33 Micrograms per liter | Geometric Coefficient of Variation 86.8 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 14; 8 hours; n= 1, 4 | 738.96 Micrograms per liter | Geometric Coefficient of Variation 79.2 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 14; 12 hours; n= 1, 4 | 757.72 Micrograms per liter | Geometric Coefficient of Variation 87.9 |
| Participants Undergoing APD | Plasma Concentration of Hepcidin | Day 14; 4 hours; n= 1, 4 | 782.59 Micrograms per liter | Geometric Coefficient of Variation 81.9 |
Secondary
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).
Time frame: 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
Population: PK Population. Only participants available at specified time points were analyzed. Due to lack of quantifiable plasma concentrations in terminal elimination phase (Day 1) of 4 metabolites GSK2391220,GSK2506102,GSK2531403,GSK2531401, terminal slope(lambda z) could not be determined,thus t1/2 could not be calculated as it depends on lambda z value.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK1278863; Day 1; n= 1, 7 | 1.6256 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK1278863; Day 14; n= 1, 4 | 1.8088 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2391220; Day 14; n= 1, 4 | 9.2225 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2487818; Day 1; n=1, 7 | 3.6560 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2487818; Day 14; n= 1, 4 | 2.9958 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2506102; Day 14; n= 1,4 | 16.2000 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531398; Day 1; n=1, 7 | 5.7900 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531398; Day 14; n= 1, 4 | 5.8275 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531403; Day 14; n= 1, 4 | 13.0606 Hours | — |
| Participants Undergoing CAPD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531401; Day 14; n= 1, 4 | 20.7794 Hours | — |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531398; Day 14; n= 1, 4 | 7.3088 Hours | Geometric Coefficient of Variation 40 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK1278863; Day 1; n= 1, 7 | 1.9870 Hours | Geometric Coefficient of Variation 25.8 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2506102; Day 14; n= 1,4 | 17.7692 Hours | Geometric Coefficient of Variation 65.4 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK1278863; Day 14; n= 1, 4 | 2.5312 Hours | Geometric Coefficient of Variation 35.7 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531401; Day 14; n= 1, 4 | 26.9981 Hours | Geometric Coefficient of Variation 54.2 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2391220; Day 14; n= 1, 4 | 10.2882 Hours | Geometric Coefficient of Variation 27.2 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531398; Day 1; n=1, 7 | 7.0659 Hours | Geometric Coefficient of Variation 35.9 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2487818; Day 1; n=1, 7 | 3.3612 Hours | Geometric Coefficient of Variation 22.7 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2531403; Day 14; n= 1, 4 | 14.5877 Hours | Geometric Coefficient of Variation 43.5 |
| Participants Undergoing APD | Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites | GSK2487818; Day 14; n= 1, 4 | 3.8955 Hours | Geometric Coefficient of Variation 25.3 |
Secondary
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.
Time frame: Day 1 and Day 14
Population: PK Population. CAPD and APD arms were combined to present data for all participants analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Participants Undergoing CAPD | Time Invariance Ratio of GSK1278863 and Metabolites | GSK1278863; n= 8 | 0.896 Ratio of AUC |
| Participants Undergoing CAPD | Time Invariance Ratio of GSK1278863 and Metabolites | GSK2487818; n= 8 | 1.007 Ratio of AUC |
| Participants Undergoing CAPD | Time Invariance Ratio of GSK1278863 and Metabolites | GSK2531398; n= 8 | 0.986 Ratio of AUC |
Secondary
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).
Time frame: 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
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=x in category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK1278863; Day 1; n=1, 7 | 0.50 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK1278863; Day 14; n= 1, 4 | 2.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2391220; Day 1; n= 1, 7 | 3.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2391220; Day 14; n= 1, 4 | 4.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2487818; Day 1; n= 1, 7 | 3.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2487818; Day 14; n= 1, 4 | 3.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2506102; Day 1; n=1, 7 | 4.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2506102; Day 14; n= 1, 4 | 4.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531398; Day 1; n= 1,7 | 4.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531398; Day 14; n= 1, 4 | 4.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531403; Day 1; n= 1, 7 | 6.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531403; Day 14; n= 1, 4 | 4.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531401; Day 1; n= 1, 7 | 8.00 Hour |
| Participants Undergoing CAPD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531401; Day 14; n= 1, 4 | 8.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531403; Day 1; n= 1, 7 | 6.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK1278863; Day 1; n=1, 7 | 1.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2506102; Day 14; n= 1, 4 | 5.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK1278863; Day 14; n= 1, 4 | 2.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531401; Day 1; n= 1, 7 | 8.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2391220; Day 1; n= 1, 7 | 4.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531398; Day 1; n= 1,7 | 4.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2391220; Day 14; n= 1, 4 | 5.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531403; Day 14; n= 1, 4 | 6.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2487818; Day 1; n= 1, 7 | 4.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531398; Day 14; n= 1, 4 | 5.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2487818; Day 14; n= 1, 4 | 4.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2531401; Day 14; n= 1, 4 | 9.00 Hour |
| Participants Undergoing APD | Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites | GSK2506102; Day 1; n=1, 7 | 8.00 Hour |