Daprodustat Hepatic Impairment Study

A Phase 1, Open-label, Non-randomized, Parallel Group, Single-dose Adaptive Study in Adults With Hepatic Impairment and Matched, Healthy Control Participants With Normal Hepatic Function

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03223337

Enrollment

Registered

2017-07-21

Start date

2017-07-24

Completion date

2018-08-20

Last updated

2019-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anaemia

Keywords

GSK1278863, Daprodustat, Healthy control, Single dose, Hepatic Impairment

Brief summary

Daprodustat (GSK1278863), is a small molecule currently in development for the treatment of anemia of chronic kidney disease (CKD). Results of the earlier studies shows that liver is involved in the clearance of Daprodustat and hence, hepatic impairment can affect Daprodustat levels in the body. This single dose study will assess the effect of liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD) of daprodustat. The study will be conducted in two parts, Part 1 will include subjects with moderate hepatic impairment and matched healthy control subjects whereas Part 2 will include subjects will either mild or severe hepatic impairment and matched healthy control subjects. Approximately 8 subjects will be included in each of the group and all subjects will receive 6 milligram (mg) of daprodustat as a single oral dose in the fasted state. Total duration of participation in the study for a subject will be up to 7 weeks.

Interventions

DRUGDaprodustat (GSK1278863)

Daprodustat (GSK1278863) 6 mg tablet will be given to all subjects as a single dose via oral route. Daprodustat (GSK1278863) is a 9.0 millimeter (mm) round, compound radius, white film coated tablet.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Masking description

This will be an open-label study and no blinding will be performed.

Intervention model description

All subjects will receive 6 mg of daprodustat as a single oral dose in parallel way throughout the study period.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

For all subjects: * Subject must be at least 18 years of age inclusive, at the time of signing the informed consent. * Hemoglobin values at screening \<=16.0 gram per deciliter (g/dL) for males and \<=14.0 g/dL for females. * Body weight \>=45 kilograms (kg) and body mass index (BMI) within the range 18-40 kg per meter square (kg/m\^2) (inclusive). * Male or female subjects will be included. A female subject is eligible to participate if she is not breastfeeding, and at least one of the following applies: Not pregnant as confirmed by two pregnancy tests; Not a woman of childbearing potential (WOCBP); For WOCBP that are currently utilizing a highly-effective contraceptive method prior to enrolment, agrees to follow the contraceptive guidance during the treatment period to the follow-up visit. * Capable of giving signed informed consent form. Additional inclusion criteria for Hepatically-Impaired subjects: * Subjects in Part 1 with Moderate Hepatic Impairment Only (Cohort 1): Is considered to have moderate hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having moderate hepatic impairment, subjects must have a Child-Pugh (Class B) score of 7-9 AND previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, computerized tomography (CT) scan, magnetic resonance imaging (MRI) or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension). * Subjects in Part 2 with Mild OR Severe Hepatic Impairment Only (Cohort 3; if conducted): Is considered to have mild or severe hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having mild OR severe hepatic impairment, subjects must have: classified as having mild hepatic impairment, subjects must have a Child- Pugh (Class A) score of 5-6 AND previous confirmation of chronic liver disease by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension); classified as having severe hepatic impairment, subjects must have Child- Pugh (Class C) score of 10-13 AND previous confirmation of chronic liver disease by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension). * Supplemental inclusion criteria for ALL hepatically-impaired subjects: Chronic (\>6 months), stable (no acute episodes of illness due to deterioration in hepatic function within the previous 1 month prior to screening) hepatic impairment due to any etiology. Subjects must also remain stable throughout the Screening period. Assessment of the stability of the subjects hepatic function will be determined by the investigator. Additional inclusion criteria for healthy control subjects: * Healthy control subjects will be matched for age +/-10 years to subjects in the respective hepatic impairment cohort but must also be at least 18 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or

Exclusion criteria

, outside the reference range for the population being studied may be included only if the investigator and/or the Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Healthy control subjects will be matched for BMI +/-15% to subjects in the respective hepatic impairment cohort but must also remain in the range of body weight \>=45 kg and BMI within the range 18-38 kg/m\^2 (inclusive).

Design outcomes

Primary

Measure	Time frame	Description
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	3 hours, 12 hours and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites (GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13)). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2) , GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Cmax of GSK1278863 and Its Metabolites.	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: T1/2 of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Tmax of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	3 hours, 12 hours and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	3 hours, 12 hours and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	3 hours, 12 hours and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818, GSK2506102, GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.

Secondary

Measure	Time frame	Description
Part 2: Cmax, EPO Following Administration of GSK1278863	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose	Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose	Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Part 2: Tmax, EPO Following Administration of GSK1278863	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose	Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose	Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Part 2: AUC (0-t, EPO) Following Administration of GSK1278863	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose	Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 16 days	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study medication.
Part 2: Number of Participants With AEs and SAEs	Up to 16 days	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment.
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Baseline (Screening) and up to Day 16	Blood samples were collected for analysis of hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 grams per liter (g/L) for hemoglobin, \<3 or \>20 x10\^9 cells per liter (cells/L) for leukocytes, \<0.8 x10\^9 cells/L for lymphocytes, \<1.5 x10\^9 cells/L for neutrophils, and \<100 or \>550 x10\^9 cells/L for platelet. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given \[e.g.\], High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Baseline (Screening) and up to Day 16	Blood samples were collected for analysis of hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 g/L for hemoglobin, \<3 or \>20 x10\^9 cells/L for leukocytes, \<0.8 x10\^9 cells/L for lymphocytes, \<1.5 x10\^9 cells/L for neutrophils, and \<100 or \>550 x10\^9 cells/L for platelet. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Baseline (Screening) and up to Day 16	Blood samples were collected for analysis of following parameters. PCI ranges were \<30g/L (albumin), \<2 or \>2.75 millimoles/L(mmol/L) (calcium), \<3 or \>9mmol/L(glucose), \>=2 times Upper limit of Normal(ULN) units/L(U/L) (alanine aminotransferase \[ALT\]), \>=2 times ULN U/L (alkaline phosphatase), \>=2 times ULN U/L(aspartate aminotransferase \[AST\]), \>=1.5 times ULN micromoles/L (µmol/L)(bilirubin), \<3 or \>5.5mmol/L(potassium), and \<130 or \>150mmol/L(sodium). Participants were counted in worst case category that their value changes to (low,within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Baseline (Screening) and up to Day 16	Blood samples were collected for analysis of following parameters. PCI ranges were \<30g/L (albumin), \<2 or \>2.75 mmol/L (calcium), \<3 or \>9mmol/L (glucose), \>=2 times ULN U/L (ALT), \>=2 times ULN U/L (alkaline phosphatase), \>=2 times ULN U/L (AST), \>=1.5 times ULN µmol/L (bilirubin), \<3 or \>5.5 mmol/L (potassium), and \<130 or \>150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.
Part 1: Number of Participants With Abnormal Urinalysis Findings	Up to Day 16	Urine samples were collected at indicated time points for the analysis of urine parameters including specific gravity and Potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine.
Part 2: Number of Participants With Abnormal Urinalysis Findings	Up to Day 16	Urine samples were collected at indicated time points for the analysis of urine parameters including specific gravity and Potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine.
Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863	Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose	Venous blood samples were collected for measurement of plasma EPO at the indicated time points. Pharmacodynamic Population comprised of all participants in the Safety Population who had at least one pharmacodynamic assessment.

Countries

United States

Participant flow

Recruitment details

This was a two part study in adults with moderate (Part 1) and potentially mild (Part 2) hepatic impairment and matched, healthy control participants with normal hepatic function. This study was conducted at two centers in the United States of America (USA).

Pre-assignment details

All participants received 6 milligrams (mg) of daprodustat (GSK1278863) as a single oral dose in the fasted state. A total number of 16 participants were enrolled in Part 1 and 21 participants were enrolled in Part 2 of the study. In total 37 participants were enrolled in the study.

Participants by arm

Arm	Count
Part 1: Moderate Hepatic Impairment Participants Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.	8
Part 1: Healthy Participants Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.	8
Part 2: Mild Hepatic Impairment Participants Participants with mild hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during part 2 of the study. This group included at least one participant with a Child-Pugh score of 5 and 6 for mild hepatic impairment.	12
Part 2: Healthy Participants Healthy control participants, matched to mild hepatic impairment participants in gender, age and BMI received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state in part 2 of the study.	9
Total	37

Baseline characteristics

Characteristic	Part 1: Moderate Hepatic Impairment Participants	Part 1: Healthy Participants	Part 2: Mild Hepatic Impairment Participants	Part 2: Healthy Participants	Total
Age, Continuous	59.5 Years STANDARD_DEVIATION 6	57.6 Years STANDARD_DEVIATION 7.15	61.9 Years STANDARD_DEVIATION 7.55	58.7 Years STANDARD_DEVIATION 8.03	59.7 Years STANDARD_DEVIATION 7.18
Race/Ethnicity, Customized ASIAN - EAST ASIAN HERITAGE	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	0 Participants	2 Participants	1 Participants	2 Participants	5 Participants
Race/Ethnicity, Customized WHITE - ARABIC/NORTH AFRICAN HERITAGE	0 Participants	0 Participants	4 Participants	1 Participants	5 Participants
Race/Ethnicity, Customized WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE	8 Participants	6 Participants	6 Participants	6 Participants	26 Participants
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants	2 Participants	6 Participants
Sex: Female, Male Male	7 Participants	7 Participants	10 Participants	7 Participants	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8	0 / 12	0 / 9
other Total, other adverse events	1 / 8	2 / 8	0 / 12	0 / 9
serious Total, serious adverse events	0 / 8	0 / 8	0 / 12	0 / 9

Outcome results

Primary

Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK1278863	3.9867 Hours	Geometric Coefficient of Variation 33.2
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hours	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	2.6559 Hours	Geometric Coefficient of Variation 38.3
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.1287 Hours	Geometric Coefficient of Variation 26
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	4.1830 Hours	Geometric Coefficient of Variation 26.9
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	3.9432 Hours	Geometric Coefficient of Variation 22.8
Part 1: Moderate Hepatic Impairment Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	3.1966 Hours	Geometric Coefficient of Variation 23.4
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	3.9414 Hours	Geometric Coefficient of Variation 33.1
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	5.6415 Hours	Geometric Coefficient of Variation 37.1
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	3.6385 Hours	Geometric Coefficient of Variation 83.8
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	2.7314 Hours	Geometric Coefficient of Variation 36.4
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hours	—
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.2641 Hours	Geometric Coefficient of Variation 56.3
Part 1: Healthy Participants	Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites	GSK1278863	4.4054 Hours	Geometric Coefficient of Variation 29.8

90% CI: [0.69, 1.1869]

90% CI: [0.5617, 0.9787]

90% CI: [0.4387, 1.2145]

90% CI: [0.9, 1.5219]

90% CI: [0.6664, 1.3786]

90% CI: [0.7833, 1.2778]

Primary

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), and GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	47.5557 Hour*nanogram per milliliter	Geometric Coefficient of Variation 67.4
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hour*nanogram per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	77.6352 Hour*nanogram per milliliter	Geometric Coefficient of Variation 56.9
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	33.9398 Hour*nanogram per milliliter	Geometric Coefficient of Variation 49.2
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	16.8212 Hour*nanogram per milliliter	Geometric Coefficient of Variation 43.9
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	52.0606 Hour*nanogram per milliliter	Geometric Coefficient of Variation 34
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK1278863	296.2407 Hour*nanogram per milliliter	Geometric Coefficient of Variation 111.1
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	39.6044 Hour*nanogram per milliliter	Geometric Coefficient of Variation 32.1
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK1278863	148.3225 Hour*nanogram per milliliter	Geometric Coefficient of Variation 31.7
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	47.1340 Hour*nanogram per milliliter	Geometric Coefficient of Variation 30.9
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	28.9896 Hour*nanogram per milliliter	Geometric Coefficient of Variation 30.3
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	11.2658 Hour*nanogram per milliliter	Geometric Coefficient of Variation 29.4
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hour*nanogram per milliliter	—
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	20.9224 Hour*nanogram per milliliter	Geometric Coefficient of Variation 27.7

90% CI: [1.1063, 3.6057]

90% CI: [1.1267, 2.4079]

90% CI: [1.0744, 2.5048]

90% CI: [1.0876, 2.0498]

90% CI: [1.1594, 2.2696]

90% CI: [0.9896, 1.7462]

Primary

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	47.2803 Hour*nanogram per milliliter	Geometric Coefficient of Variation 67.7
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hour*nanogram per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	77.4861 Hour*nanogram per milliliter	Geometric Coefficient of Variation 57
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	33.8516 Hour*nanogram per milliliter	Geometric Coefficient of Variation 49.3
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	16.7177 Hour*nanogram per milliliter	Geometric Coefficient of Variation 43.9
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	51.9052 Hour*nanogram per milliliter	Geometric Coefficient of Variation 34.1
Part 1: Moderate Hepatic Impairment Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK1278863	296.1035 Hour*nanogram per milliliter	Geometric Coefficient of Variation 111.2
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	39.4939 Hour*nanogram per milliliter	Geometric Coefficient of Variation 32.3
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK1278863	148.2504 Hour*nanogram per milliliter	Geometric Coefficient of Variation 31.8
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	46.9368 Hour*nanogram per milliliter	Geometric Coefficient of Variation 31
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	28.7930 Hour*nanogram per milliliter	Geometric Coefficient of Variation 30.6
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	11.0208 Hour*nanogram per milliliter	Geometric Coefficient of Variation 30.9
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hour*nanogram per milliliter	—
Part 1: Healthy Participants	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	20.8451 Hour*nanogram per milliliter	Geometric Coefficient of Variation 27.8

90% CI: [1.1061, 3.6066]

90% CI: [1.1285, 2.415]

90% CI: [1.0732, 2.5125]

90% CI: [1.0994, 2.093]

90% CI: [1.1599, 2.2736]

90% CI: [0.9887, 1.747]

Primary

Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	10.022 Nanogram per milliliter	Geometric Coefficient of Variation 55
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Nanogram per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	13.046 Nanogram per milliliter	Geometric Coefficient of Variation 46.2
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	5.946 Nanogram per milliliter	Geometric Coefficient of Variation 41.7
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	2.650 Nanogram per milliliter	Geometric Coefficient of Variation 34.6
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	7.411 Nanogram per milliliter	Geometric Coefficient of Variation 35
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK1278863	139.705 Nanogram per milliliter	Geometric Coefficient of Variation 108.8
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	7.120 Nanogram per milliliter	Geometric Coefficient of Variation 28
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK1278863	70.607 Nanogram per milliliter	Geometric Coefficient of Variation 51.7
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	10.199 Nanogram per milliliter	Geometric Coefficient of Variation 28.7
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	8.025 Nanogram per milliliter	Geometric Coefficient of Variation 28.5
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	2.245 Nanogram per milliliter	Geometric Coefficient of Variation 23
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Nanogram per milliliter	—
Part 1: Healthy Participants	Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	4.672 Nanogram per milliliter	Geometric Coefficient of Variation 24.1

90% CI: [1.0557, 3.7084]

90% CI: [0.9241, 1.7705]

90% CI: [0.8675, 1.7974]

90% CI: [0.9165, 1.5197]

90% CI: [0.952, 1.7012]

90% CI: [0.7927, 1.3668]

Primary

Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	0.5756 Percentage of AUCex	Standard Deviation 0.89564
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Percentage of AUCex	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	0.1919 Percentage of AUCex	Standard Deviation 0.14164
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	0.2598 Percentage of AUCex	Standard Deviation 0.10004
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	0.6147 Percentage of AUCex	Standard Deviation 0.17403
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	0.2983 Percentage of AUCex	Standard Deviation 0.27141
Part 1: Moderate Hepatic Impairment Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK1278863	0.0463 Percentage of AUCex	Standard Deviation 0.03971
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	0.2787 Percentage of AUCex	Standard Deviation 0.15617
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK1278863	0.0486 Percentage of AUCex	Standard Deviation 0.03445
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	0.4176 Percentage of AUCex	Standard Deviation 0.38893
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	0.6763 Percentage of AUCex	Standard Deviation 0.61031
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	2.1559 Percentage of AUCex	Standard Deviation 2.01781
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Percentage of AUCex	—
Part 1: Healthy Participants	Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	0.3689 Percentage of AUCex	Standard Deviation 0.26189

Primary

Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (MEDIAN)
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	3.00 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hours
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	3.00 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.50 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	3.50 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	4.00 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK1278863	1.50 Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	4.00 Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK1278863	2.00 Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	3.50 Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	3.00 Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	4.00 Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	NA Hours
Part 1: Healthy Participants	Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.50 Hours

p-value: 0.682290% CI: [-1, 0.5]Wilcoxon (Mann-Whitney)

p-value: 0.576790% CI: [-1, 1]Wilcoxon (Mann-Whitney)

p-value: 0.58890% CI: [-1, 1.5]Wilcoxon (Mann-Whitney)

p-value: 0.771690% CI: [-1, 1]Wilcoxon (Mann-Whitney)

p-value: 0.409390% CI: [-1, 2]Wilcoxon (Mann-Whitney)

p-value: 0.983790% CI: [-1, 1]Wilcoxon (Mann-Whitney)

Primary

Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites

Time frame: 3 hours, 12 hours and 24 hours post-dose

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours	0.27989 Nanograms per milliliter	Standard Deviation 0.261668
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours	NA Nanograms per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours	NA Nanograms per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours	4.47750 Nanograms per milliliter	Standard Deviation 1.779468
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours	0.76525 Nanograms per milliliter	Standard Deviation 0.656087
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours	0.06460 Nanograms per milliliter	Standard Deviation 0.089209
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours	3.24463 Nanograms per milliliter	Standard Deviation 1.506964
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours	0.29301 Nanograms per milliliter	Standard Deviation 0.338773
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours	0.01201 Nanograms per milliliter	Standard Deviation 0.023617
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours	0.64588 Nanograms per milliliter	Standard Deviation 0.242321
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours	0.13024 Nanograms per milliliter	Standard Deviation 0.109089
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours	0.00923 Nanograms per milliliter	Standard Deviation 0.026092
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours	3.86250 Nanograms per milliliter	Standard Deviation 1.402241
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours	0.71075 Nanograms per milliliter	Standard Deviation 0.601452
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours	0.06315 Nanograms per milliliter	Standard Deviation 0.104994
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours	1.42725 Nanograms per milliliter	Standard Deviation 0.552287
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours	0.22973 Nanograms per milliliter	Standard Deviation 0.199514
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours	0.01470 Nanograms per milliliter	Standard Deviation 0.02858
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours	2.25375 Nanograms per milliliter	Standard Deviation 0.646771
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours	0.63125 Nanograms per milliliter	Standard Deviation 0.379804
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours	0.07580 Nanograms per milliliter	Standard Deviation 0.110738
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours	0.04143 Nanograms per milliliter	Standard Deviation 0.03114
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours	0.11076 Nanograms per milliliter	Standard Deviation 0.070114
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours	2.03738 Nanograms per milliliter	Standard Deviation 0.807331
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours	0.06548 Nanograms per milliliter	Standard Deviation 0.035504
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours	2.85875 Nanograms per milliliter	Standard Deviation 1.129961
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours	2.57000 Nanograms per milliliter	Standard Deviation 1.010262
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours	0.22463 Nanograms per milliliter	Standard Deviation 0.119826
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours	0.01053 Nanograms per milliliter	Standard Deviation 0.020023
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours	0.00963 Nanograms per milliliter	Standard Deviation 0.017963
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours	0.23938 Nanograms per milliliter	Standard Deviation 0.121781
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours	1.86813 Nanograms per milliliter	Standard Deviation 0.760479
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours	0.04769 Nanograms per milliliter	Standard Deviation 0.031411
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours	0.00829 Nanograms per milliliter	Standard Deviation 0.015374
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours	0.32075 Nanograms per milliliter	Standard Deviation 0.163981
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours	0.43175 Nanograms per milliliter	Standard Deviation 0.165059
Part 1: Healthy Participants	Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours	0.89338 Nanograms per milliliter	Standard Deviation 0.334179

Primary

Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites; GSK2391220 (M2), GSK2506104 (M3), GSK2487818, GSK2506102, GSK2531398 (M6), GSK2531401 (M13). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.

Time frame: 3 hours, 12 hours and 24 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours; n=2,8	0.3508 Percentage of unbound drug in plasma	Standard Deviation 0.00191
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours; n=8,8	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours; n=8,8	0.3379 Percentage of unbound drug in plasma	Standard Deviation 0.03573
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours; n=8, 8	0.2469 Percentage of unbound drug in plasma	Standard Deviation 0.04315
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours; n=8,8	0.3540 Percentage of unbound drug in plasma	Standard Deviation 0.02186
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours; n=8, 8	0.2550 Percentage of unbound drug in plasma	Standard Deviation 0.03166
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours; n=8, 8	0.2565 Percentage of unbound drug in plasma	Standard Deviation 0.04573
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours; n=2, 8	0.3005 Percentage of unbound drug in plasma	Standard Deviation 0.03734
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours; n=8, 8	0.3519 Percentage of unbound drug in plasma	Standard Deviation 0.04431
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours; n=8, 6	0.2517 Percentage of unbound drug in plasma	Standard Deviation 0.04022
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours; n=8, 8	0.3771 Percentage of unbound drug in plasma	Standard Deviation 0.02114
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours; n=4,2	0.3861 Percentage of unbound drug in plasma	Standard Deviation 0.02827
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours; n=6, 2	0.3817 Percentage of unbound drug in plasma	Standard Deviation 0.04449
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours; n=1, 8	0.2723 Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours; n=8,8	0.3080 Percentage of unbound drug in plasma	Standard Deviation 0.03085
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours; n=8,7	0.3071 Percentage of unbound drug in plasma	Standard Deviation 0.03419
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours; n=8, 8	0.0034 Percentage of unbound drug in plasma	Standard Deviation 0.00109
Part 1: Moderate Hepatic Impairment Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours; n=8, 8	0.0028 Percentage of unbound drug in plasma	Standard Deviation 0.00019
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours; n=8,8	0.3495 Percentage of unbound drug in plasma	Standard Deviation 0.05135
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours; n=8,8	0.3355 Percentage of unbound drug in plasma	Standard Deviation 0.02172
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours; n=4,2	0.3902 Percentage of unbound drug in plasma	Standard Deviation 0.07149
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours; n=8,8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours; n=8,7	0.2402 Percentage of unbound drug in plasma	Standard Deviation 0.02431
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours; n=2,8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours; n=8, 8	0.2441 Percentage of unbound drug in plasma	Standard Deviation 0.03397
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours; n=8, 6	0.2335 Percentage of unbound drug in plasma	Standard Deviation 0.02679
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours; n=8, 8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours; n=8, 8	0.2461 Percentage of unbound drug in plasma	Standard Deviation 0.03264
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours; n=8, 8	0.2295 Percentage of unbound drug in plasma	Standard Deviation 0.01509
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours; n=2, 8	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours; n=8, 8	0.3844 Percentage of unbound drug in plasma	Standard Deviation 0.06838
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours; n=8, 8	0.3565 Percentage of unbound drug in plasma	Standard Deviation 0.02558
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours; n=6, 2	0.3716 Percentage of unbound drug in plasma	Standard Deviation 0.02411
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours; n=8,8	0.2925 Percentage of unbound drug in plasma	Standard Deviation 0.01981
Part 1: Healthy Participants	Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours; n=1, 8	NA Percentage of unbound drug in plasma	—

Primary

Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	63.6211 Hour*nanogram per milliliter	Geometric Coefficient of Variation 40.1
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	91.7692 Hour*nanogram per milliliter	Geometric Coefficient of Variation 41
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	91.3799 Hour*nanogram per milliliter	Geometric Coefficient of Variation 44.7
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	41.4666 Hour*nanogram per milliliter	Geometric Coefficient of Variation 31.2
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	19.4020 Hour*nanogram per milliliter	Geometric Coefficient of Variation 36.6
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	46.7001 Hour*nanogram per milliliter	Geometric Coefficient of Variation 66.5
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK1278863	299.8773 Hour*nanogram per milliliter	Geometric Coefficient of Variation 39.9
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	31.9797 Hour*nanogram per milliliter	Geometric Coefficient of Variation 40.9
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK1278863	205.7559 Hour*nanogram per milliliter	Geometric Coefficient of Variation 37.2
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	47.1647 Hour*nanogram per milliliter	Geometric Coefficient of Variation 26.9
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	31.7637 Hour*nanogram per milliliter	Geometric Coefficient of Variation 28.4
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	11.3374 Hour*nanogram per milliliter	Geometric Coefficient of Variation 26.7
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	50.1154 Hour*nanogram per milliliter	Geometric Coefficient of Variation 28.3
Part 1: Healthy Participants	Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	21.0066 Hour*nanogram per milliliter	Geometric Coefficient of Variation 23.5

90% CI: [1.035, 2.0523]

90% CI: [1.3919, 2.6968]

90% CI: [1.3342, 2.5133]

90% CI: [1.4654, 2.7378]

90% CI: [1.2818, 2.2847]

90% CI: [1.5365, 2.536]

90% CI: [0.9081, 2.3484]

Primary

Part 2: AUC (0-t) of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	63.4564 Hour*nanogram per milliliter	Geometric Coefficient of Variation 40.3
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	91.5334 Hour*nanogram per milliliter	Geometric Coefficient of Variation 41.2
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	91.1105 Hour*nanogram per milliliter	Geometric Coefficient of Variation 44.9
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	41.3456 Hour*nanogram per milliliter	Geometric Coefficient of Variation 31.4
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	19.3023 Hour*nanogram per milliliter	Geometric Coefficient of Variation 36.8
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	46.5914 Hour*nanogram per milliliter	Geometric Coefficient of Variation 66.8
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK1278863	299.5322 Hour*nanogram per milliliter	Geometric Coefficient of Variation 39.9
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2531401 (M13)	31.8113 Hour*nanogram per milliliter	Geometric Coefficient of Variation 41.3
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK1278863	205.6322 Hour*nanogram per milliliter	Geometric Coefficient of Variation 37.2
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2391220 (M2)	46.7771 Hour*nanogram per milliliter	Geometric Coefficient of Variation 27.9
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2487818 (M4)	31.4750 Hour*nanogram per milliliter	Geometric Coefficient of Variation 29
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2506102 (M5)	11.1555 Hour*nanogram per milliliter	Geometric Coefficient of Variation 27.1
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2506104 (M3)	49.7669 Hour*nanogram per milliliter	Geometric Coefficient of Variation 29.2
Part 1: Healthy Participants	Part 2: AUC (0-t) of GSK1278863 and Its Metabolites	GSK2531398 (M6)	20.8080 Hour*nanogram per milliliter	Geometric Coefficient of Variation 24

90% CI: [1.335, 2.534]

90% CI: [1.4711, 2.763]

90% CI: [1.2932, 2.3151]

90% CI: [1.5426, 2.5594]

90% CI: [0.9086, 2.3609]

90% CI: [1.0344, 2.0513]

90% CI: [1.3935, 2.7224]

Primary

Part 2: Cmax of GSK1278863 and Its Metabolites.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2487818 (M4)	13.614 Nanogram per milliliter	Geometric Coefficient of Variation 34.7
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2506104 (M3)	15.475 Nanogram per milliliter	Geometric Coefficient of Variation 38.8
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2391220 (M2)	15.792 Nanogram per milliliter	Geometric Coefficient of Variation 40.8
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2531398 (M6)	7.333 Nanogram per milliliter	Geometric Coefficient of Variation 28.2
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2506102 (M5)	3.241 Nanogram per milliliter	Geometric Coefficient of Variation 35.7
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2531401 (M13)	6.791 Nanogram per milliliter	Geometric Coefficient of Variation 65.5
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK1278863	113.232 Nanogram per milliliter	Geometric Coefficient of Variation 42.6
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2531401 (M13)	5.081 Nanogram per milliliter	Geometric Coefficient of Variation 43.4
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK1278863	112.142 Nanogram per milliliter	Geometric Coefficient of Variation 35.7
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2391220 (M2)	8.846 Nanogram per milliliter	Geometric Coefficient of Variation 40
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2487818 (M4)	7.723 Nanogram per milliliter	Geometric Coefficient of Variation 35.6
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2506102 (M5)	1.975 Nanogram per milliliter	Geometric Coefficient of Variation 33.4
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2506104 (M3)	8.926 Nanogram per milliliter	Geometric Coefficient of Variation 37.9
Part 1: Healthy Participants	Part 2: Cmax of GSK1278863 and Its Metabolites.	GSK2531398 (M6)	4.010 Nanogram per milliliter	Geometric Coefficient of Variation 31.7

90% CI: [0.7122, 1.4316]

90% CI: [1.2498, 2.5498]

90% CI: [1.2343, 2.4353]

90% CI: [1.2898, 2.4092]

90% CI: [1.2055, 2.2347]

90% CI: [1.3992, 2.3904]

90% CI: [0.8288, 2.1557]

Primary

Part 2: Percentage AUCex of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2487818 (M4)	0.2584 Percentage of AUCex	Standard Deviation 0.30727
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2506104 (M3)	0.2565 Percentage of AUCex	Standard Deviation 0.28382
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2391220 (M2)	0.2943 Percentage of AUCex	Standard Deviation 0.32698
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2531398 (M6)	0.2915 Percentage of AUCex	Standard Deviation 0.2535
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2506102 (M5)	0.5138 Percentage of AUCex	Standard Deviation 0.22859
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2531401 (M13)	0.2327 Percentage of AUCex	Standard Deviation 0.23338
Part 1: Moderate Hepatic Impairment Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK1278863	0.1148 Percentage of AUCex	Standard Deviation 0.26035
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2531401 (M13)	0.5256 Percentage of AUCex	Standard Deviation 0.46352
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK1278863	0.0601 Percentage of AUCex	Standard Deviation 0.06032
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2391220 (M2)	0.8105 Percentage of AUCex	Standard Deviation 1.60084
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2487818 (M4)	0.9054 Percentage of AUCex	Standard Deviation 0.89147
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2506102 (M5)	1.5924 Percentage of AUCex	Standard Deviation 1.693
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2506104 (M3)	0.6875 Percentage of AUCex	Standard Deviation 1.33005
Part 1: Healthy Participants	Part 2: Percentage AUCex of GSK1278863 and Its Metabolites	GSK2531398 (M6)	0.9412 Percentage of AUCex	Standard Deviation 0.94415

Primary

Part 2: T1/2 of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2487818 (M4)	4.1059 Hours	Geometric Coefficient of Variation 47.8
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2506104 (M3)	4.6675 Hours	Geometric Coefficient of Variation 20.2
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2391220 (M2)	4.8118 Hours	Geometric Coefficient of Variation 21.2
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.8096 Hours	Geometric Coefficient of Variation 38.4
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2506102 (M5)	3.4087 Hours	Geometric Coefficient of Variation 30.8
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2531401 (M13)	4.2869 Hours	Geometric Coefficient of Variation 21.2
Part 1: Moderate Hepatic Impairment Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK1278863	4.5251 Hours	Geometric Coefficient of Variation 27.4
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2531401 (M13)	3.5510 Hours	Geometric Coefficient of Variation 34.2
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK1278863	4.2792 Hours	Geometric Coefficient of Variation 38.7
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2391220 (M2)	4.7439 Hours	Geometric Coefficient of Variation 49.6
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2487818 (M4)	3.0578 Hours	Geometric Coefficient of Variation 88.9
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2506102 (M5)	3.3108 Hours	Geometric Coefficient of Variation 56.7
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2506104 (M3)	4.4967 Hours	Geometric Coefficient of Variation 45
Part 1: Healthy Participants	Part 2: T1/2 of GSK1278863 and Its Metabolites	GSK2531398 (M6)	2.9947 Hours	Geometric Coefficient of Variation 57.1

90% CI: [0.7876, 1.4197]

90% CI: [0.7332, 1.4032]

90% CI: [0.7695, 1.4002]

90% CI: [0.7635, 2.3615]

90% CI: [0.6996, 1.5151]

90% CI: [0.8409, 1.9245]

90% CI: [0.9398, 1.5508]

Primary

Part 2: Tmax of GSK1278863 and Its Metabolites

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Arm	Measure	Group	Value (MEDIAN)
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2531401 (M13)	4.00 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK1278863	1.50 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2391220 (M2)	3.00 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2487818 (M4)	3.00 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2506102 (M5)	3.50 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2506104 (M3)	3.50 Hours
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.00 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2531401 (M13)	4.00 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2506102 (M5)	3.00 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK1278863	1.50 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2531398 (M6)	3.00 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2391220 (M2)	3.00 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2506104 (M3)	3.00 Hours
Part 1: Healthy Participants	Part 2: Tmax of GSK1278863 and Its Metabolites	GSK2487818 (M4)	3.00 Hours

p-value: 0.622490% CI: [-1, 0.5]Wilcoxon (Mann-Whitney)

p-value: 0.804290% CI: [-1, 0]Wilcoxon (Mann-Whitney)

p-value: 0.842390% CI: [-1, 1]Wilcoxon (Mann-Whitney)

p-value: 0.520790% CI: [-1, 1]Wilcoxon (Mann-Whitney)

p-value: 0.842390% CI: [-1, 1]Wilcoxon (Mann-Whitney)

p-value: 190% CI: [-1, 1]Wilcoxon (Mann-Whitney)

p-value: 0.804290% CI: [0, 1]Wilcoxon (Mann-Whitney)

Primary

Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites

Time frame: 3 hours, 12 hours and 24 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours; n=6, 6	1.24213 Nanograms per milliliter	Standard Deviation 2.475347
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours; n=7, 6	0.04343 Nanograms per milliliter	Standard Deviation 0.114901
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours; n=7, 6	NA Nanograms per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours; n=8, 7	5.32625 Nanograms per milliliter	Standard Deviation 2.139472
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours; n=8, 7	0.81263 Nanograms per milliliter	Standard Deviation 0.600031
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours; n=8, 7	0.30654 Nanograms per milliliter	Standard Deviation 0.729605
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours; n=8,7	3.91375 Nanograms per milliliter	Standard Deviation 1.441219
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours; n=8,7	0.40141 Nanograms per milliliter	Standard Deviation 0.560638
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours; n=8,7	0.00839 Nanograms per milliliter	Standard Deviation 0.015586
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours; n=8,7	0.78213 Nanograms per milliliter	Standard Deviation 0.314177
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours; n=8,7	0.25856 Nanograms per milliliter	Standard Deviation 0.425759
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours; n=8,7	NA Nanograms per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours; n=8,7	4.68625 Nanograms per milliliter	Standard Deviation 1.839883
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours; n=8,7	0.75350 Nanograms per milliliter	Standard Deviation 0.496638
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours; n=8,7	0.04093 Nanograms per milliliter	Standard Deviation 0.029445
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours; n=8,7	1.86763 Nanograms per milliliter	Standard Deviation 0.713958
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours; n=8,7	0.34200 Nanograms per milliliter	Standard Deviation 0.412505
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours; n=8,7	NA Nanograms per milliliter	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours; n=8,7	2.47825 Nanograms per milliliter	Standard Deviation 0.965944
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours; n=8,7	0.75363 Nanograms per milliliter	Standard Deviation 0.597207
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours; n=8,7	0.29830 Nanograms per milliliter	Standard Deviation 0.720919
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours; n=8,7	0.04796 Nanograms per milliliter	Standard Deviation 0.03551
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours; n=6, 6	0.15692 Nanograms per milliliter	Standard Deviation 0.138726
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours; n=8,7	1.26771 Nanograms per milliliter	Standard Deviation 0.871839
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours; n=7, 6	0.01527 Nanograms per milliliter	Standard Deviation 0.037396
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours; n=8,7	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours; n=7, 6	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours; n=8,7	0.07879 Nanograms per milliliter	Standard Deviation 0.023474
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours; n=8, 7	2.13700 Nanograms per milliliter	Standard Deviation 1.276959
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours; n=8,7	1.94271 Nanograms per milliliter	Standard Deviation 1.26297
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours; n=8, 7	0.24371 Nanograms per milliliter	Standard Deviation 0.079803
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours; n=8,7	0.00454 Nanograms per milliliter	Standard Deviation 0.012019
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours; n=8, 7	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours; n=8,7	0.27014 Nanograms per milliliter	Standard Deviation 0.12283
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours; n=8,7	1.57633 Nanograms per milliliter	Standard Deviation 0.937244
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours; n=8,7	NA Nanograms per milliliter	—
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours; n=8,7	0.07793 Nanograms per milliliter	Standard Deviation 0.0333
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours; n=8,7	0.00819 Nanograms per milliliter	Standard Deviation 0.021657
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours; n=8,7	0.00454 Nanograms per milliliter	Standard Deviation 0.012019
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours; n=8,7	0.29429 Nanograms per milliliter	Standard Deviation 0.153615
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours; n=8,7	0.31091 Nanograms per milliliter	Standard Deviation 0.213793
Part 1: Healthy Participants	Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours; n=8,7	0.73530 Nanograms per milliliter	Standard Deviation 0.451869

Primary

Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK1278863 and its metabolites (GSK2391220 (M2), GSK2506104 (M3), GSK2487818 (M4), GSK2506102 (M5), GSK2531398 (M6), GSK2531401 (M13)). Pharmacokinetic parameters were determined using standard non-compartmental methods. Unbound fraction is the percentage of unbound drug in plasma calculated as unbound concentration divided by total concentration.

Time frame: 3 hours, 12 hours and 24 hours post-dose

Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).

Arm	Measure	Group	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours; n=7, 7	0.2500 Percentage of unbound drug in plasma	Standard Deviation 0.03259
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours; n=6, 6	0.0134 Percentage of unbound drug in plasma	Standard Deviation 0.02369
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours; n=1, 1	0.1231 Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours; n=8,7	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours; n=8, 7	0.3191 Percentage of unbound drug in plasma	Standard Deviation 0.02263
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours; n=7, 7	0.3305 Percentage of unbound drug in plasma	Standard Deviation 0.03497
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours; n=5, 7	0.4099 Percentage of unbound drug in plasma	Standard Deviation 0.04797
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours; n=8, 7	0.2762 Percentage of unbound drug in plasma	Standard Deviation 0.02792
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours; n=7, 7	0.2850 Percentage of unbound drug in plasma	Standard Deviation 0.0311
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours; n=2, 1	0.3116 Percentage of unbound drug in plasma	Standard Deviation 0.07106
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours; n=8, 6	0.2339 Percentage of unbound drug in plasma	Standard Deviation 0.02704
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours; n=7, 6	0.2483 Percentage of unbound drug in plasma	Standard Deviation 0.03166
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours; n=8, 7	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours; n=8, 7	0.2904 Percentage of unbound drug in plasma	Standard Deviation 0.0248
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours; n=7, 7	0.2970 Percentage of unbound drug in plasma	Standard Deviation 0.02959
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours; n=6, 1	0.3267 Percentage of unbound drug in plasma	Standard Deviation 0.03171
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours; n=8, 7	0.2491 Percentage of unbound drug in plasma	Standard Deviation 0.02989
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours; n=8, 7	NA Percentage of unbound drug in plasma	—
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours; n=8, 7	0.3595 Percentage of unbound drug in plasma	Standard Deviation 0.02324
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours; n=7, 7	0.3527 Percentage of unbound drug in plasma	Standard Deviation 0.03957
Part 1: Moderate Hepatic Impairment Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours; n=5, 1	0.4154 Percentage of unbound drug in plasma	Standard Deviation 0.03151
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 3 hours; n=8, 7	0.2444 Percentage of unbound drug in plasma	Standard Deviation 0.04833
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 12 hours; n=7, 6	0.2191 Percentage of unbound drug in plasma	Standard Deviation 0.02903
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 3 hours; n=6, 6	0.0032 Percentage of unbound drug in plasma	Standard Deviation 0.0009
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 12 hours; n=7, 7	0.2346 Percentage of unbound drug in plasma	Standard Deviation 0.02031
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 12 hours; n=1, 1	0.1246 Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 24 hours; n=8, 7	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK1278863; 24 hours; n=8,7	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 24 hours; n=5, 1	0.3845 Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 3 hours; n=8, 7	0.3343 Percentage of unbound drug in plasma	Standard Deviation 0.06101
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 3 hours; n=8, 7	0.2938 Percentage of unbound drug in plasma	Standard Deviation 0.02618
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 12 hours; n=7, 7	0.3174 Percentage of unbound drug in plasma	Standard Deviation 0.02174
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531398 (M6); 24 hours; n=8, 7	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2391220 (M2); 24 hours; n=5, 7	NA Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 12 hours; n=7, 7	0.2845 Percentage of unbound drug in plasma	Standard Deviation 0.02193
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 3 hours; n=8, 7	0.2857 Percentage of unbound drug in plasma	Standard Deviation 0.03897
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 12 hours; n=7, 7	0.3386 Percentage of unbound drug in plasma	Standard Deviation 0.0158
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 12 hours; n=7, 7	0.2766 Percentage of unbound drug in plasma	Standard Deviation 0.03608
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506104 (M3); 24 hours; n=6, 1	0.3016 Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2487818 (M4); 24 hours; n=2, 1	0.3387 Percentage of unbound drug in plasma	—
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2531401 (M13); 3 hours; n=8, 7	0.3569 Percentage of unbound drug in plasma	Standard Deviation 0.03504
Part 1: Healthy Participants	Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites	GSK2506102 (M5); 3 hours; n=8, 6	0.2171 Percentage of unbound drug in plasma	Standard Deviation 0.06728

Secondary

Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863

Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Pharmacodynamic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863	1262.3724 Hours* International units per liter	Standard Deviation 1148.34702
Part 1: Healthy Participants	Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863	697.7140 Hours* International units per liter	Standard Deviation 393.05978

Secondary

Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863

Venous blood samples were collected for measurement of plasma EPO at the indicated time points. Pharmacodynamic Population comprised of all participants in the Safety Population who had at least one pharmacodynamic assessment.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Pharmacodynamic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863	48.898 International units per liter	Standard Deviation 36.8476
Part 1: Healthy Participants	Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863	28.391 International units per liter	Standard Deviation 13.1904

Secondary

Part 1: Number of Participants With Abnormal Urinalysis Findings

Urine samples were collected at indicated time points for the analysis of urine parameters including specific gravity and Potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase in urine.

Time frame: Up to Day 16

Population: Safety Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Abnormal Urinalysis Findings	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Abnormal Urinalysis Findings	0 Participants

Secondary

Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study medication.

Time frame: Up to 16 days

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any SAE	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any AE	1 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any SAE	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Any AE	2 Participants

Secondary

Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Blood samples were collected for analysis of following parameters. PCI ranges were \<30g/L (albumin), \<2 or \>2.75 millimoles/L(mmol/L) (calcium), \<3 or \>9mmol/L(glucose), \>=2 times Upper limit of Normal(ULN) units/L(U/L) (alanine aminotransferase \[ALT\]), \>=2 times ULN U/L (alkaline phosphatase), \>=2 times ULN U/L(aspartate aminotransferase \[AST\]), \>=1.5 times ULN micromoles/L (µmol/L)(bilirubin), \<3 or \>5.5mmol/L(potassium), and \<130 or \>150mmol/L(sodium). Participants were counted in worst case category that their value changes to (low,within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.

Time frame: Baseline (Screening) and up to Day 16

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT;To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT ; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To within Range or No Change	6 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To High	2 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST;To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To Low	1 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To within Range or No Change	7 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT ; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT;To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST;To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To within Range or No Change	8 Participants

Secondary

Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

Blood samples were collected for analysis of hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 grams per liter (g/L) for hemoglobin, \<3 or \>20 x10\^9 cells per liter (cells/L) for leukocytes, \<0.8 x10\^9 cells/L for lymphocytes, \<1.5 x10\^9 cells/L for neutrophils, and \<100 or \>550 x10\^9 cells/L for platelet. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given \[e.g.\], High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.

Time frame: Baseline (Screening) and up to Day 16

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hematocrit; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hematocrit; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hematocrit; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hemoglobin; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hemoglobin; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hemoglobin; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Leukocytes; To Low	1 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Leukocytes; To within Range or No Change	7 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Leukocytes; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Lymphocytes; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Lymphocytes; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Lymphocytes; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Neutrophils; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Neutrophils; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Neutrophils; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Platelets; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Platelets; To within Range or No Change	8 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Platelets; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Neutrophils; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hematocrit; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Lymphocytes; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hematocrit; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Platelets; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hematocrit; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Lymphocytes; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hemoglobin; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Neutrophils; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hemoglobin; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Lymphocytes; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Hemoglobin; To High	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Platelets; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Leukocytes; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Neutrophils; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Leukocytes; To within Range or No Change	8 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Platelets; To Low	0 Participants
Part 1: Healthy Participants	Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline	Leukocytes; To High	0 Participants

Secondary

Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863

Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Pharmacodynamic Population

Arm	Measure	Value (MEDIAN)
Part 1: Moderate Hepatic Impairment Participants	Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863	10.0 Hours
Part 1: Healthy Participants	Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863	10.0 Hours

Secondary

Part 2: AUC (0-t, EPO) Following Administration of GSK1278863

Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Pharmacodynamic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: AUC (0-t, EPO) Following Administration of GSK1278863	1258.6211 Hours* International units per liter	Standard Deviation 683.32848
Part 1: Healthy Participants	Part 2: AUC (0-t, EPO) Following Administration of GSK1278863	1061.7549 Hours* International units per liter	Standard Deviation 647.67154

Secondary

Part 2: Cmax, EPO Following Administration of GSK1278863

Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Pharmacodynamic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1: Moderate Hepatic Impairment Participants	Part 2: Cmax, EPO Following Administration of GSK1278863	43.933 International units per liter	Standard Deviation 20.2602
Part 1: Healthy Participants	Part 2: Cmax, EPO Following Administration of GSK1278863	45.871 International units per liter	Standard Deviation 35.1537

Secondary

Part 2: Number of Participants With Abnormal Urinalysis Findings

Time frame: Up to Day 16

Population: Safety Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Abnormal Urinalysis Findings	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Abnormal Urinalysis Findings	0 Participants

Secondary

Part 2: Number of Participants With AEs and SAEs

Time frame: Up to 16 days

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With AEs and SAEs	Any SAE	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With AEs and SAEs	Any AE	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With AEs and SAEs	Any SAE	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With AEs and SAEs	Any AE	0 Participants

Secondary

Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Blood samples were collected for analysis of following parameters. PCI ranges were \<30g/L (albumin), \<2 or \>2.75 mmol/L (calcium), \<3 or \>9mmol/L (glucose), \>=2 times ULN U/L (ALT), \>=2 times ULN U/L (alkaline phosphatase), \>=2 times ULN U/L (AST), \>=1.5 times ULN µmol/L (bilirubin), \<3 or \>5.5 mmol/L (potassium), and \<130 or \>150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed To Low and To High, so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.

Time frame: Baseline (Screening) and up to Day 16

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT ; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT;To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST;To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT ; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To within Range or No Change	10 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To High	2 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To within Range or No Change	12 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Bilirubin; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Calcium; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT ; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT;To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	ALT ; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Albumin; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Alkaline Phosphatase; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	AST;To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Glucose; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Potassium; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Sodium; To within Range or No Change	9 Participants

Secondary

Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Blood samples were collected for analysis of hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were \<0.075 or \>0.54 proportion of red blood cells in blood for hematocrit, \<25 or \>180 g/L for hemoglobin, \<3 or \>20 x10\^9 cells/L for leukocytes, \<0.8 x10\^9 cells/L for lymphocytes, \<1.5 x10\^9 cells/L for neutrophils, and \<100 or \>550 x10\^9 cells/L for platelet. Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Baseline is defined as latest non-missing scheduled pre-dose assessment.

Time frame: Baseline (Screening) and up to Day 16

Population: Safety Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hemoglobin; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Lymphocytes; To Low	1 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hematocrit; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Lymphocytes; To within Range or No Change	11 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hemoglobin; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Lymphocytes; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hematocrit; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Neutrophils; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Leukocytes; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Neutrophils; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hemoglobin; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Neutrophils; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Leukocytes; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Platelets; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hematocrit; To Low	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Platelets; To within Range or No Change	12 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Leukocytes; To High	0 Participants
Part 1: Moderate Hepatic Impairment Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Platelets; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Leukocytes; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hematocrit; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hematocrit; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hematocrit; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hemoglobin; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hemoglobin; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Hemoglobin; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Leukocytes; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Leukocytes; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Platelets; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Lymphocytes; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Lymphocytes; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Lymphocytes; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Neutrophils; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Neutrophils; To within Range or No Change	9 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Neutrophils; To High	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Platelets; To Low	0 Participants
Part 1: Healthy Participants	Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline	Platelets; To within Range or No Change	9 Participants

Secondary

Part 2: Tmax, EPO Following Administration of GSK1278863

Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.

Time frame: Pre-dose, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, and 48 hours post-dose

Population: Pharmacodynamic Population

Arm	Measure	Value (MEDIAN)
Part 1: Moderate Hepatic Impairment Participants	Part 2: Tmax, EPO Following Administration of GSK1278863	10.0 Hours
Part 1: Healthy Participants	Part 2: Tmax, EPO Following Administration of GSK1278863	10.0 Hours

Source: ClinicalTrials.gov · Data processed: Feb 12, 2026

Daprodustat Hepatic Impairment Study

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Masking description

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites

Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites

Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites

Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites

Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites

Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites

Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites

Part 2: AUC (0-t) of GSK1278863 and Its Metabolites

Part 2: Cmax of GSK1278863 and Its Metabolites.

Part 2: Percentage AUCex of GSK1278863 and Its Metabolites

Part 2: T1/2 of GSK1278863 and Its Metabolites

Part 2: Tmax of GSK1278863 and Its Metabolites

Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites

Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites

Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863

Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863

Part 1: Number of Participants With Abnormal Urinalysis Findings

Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline

Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863

Part 2: AUC (0-t, EPO) Following Administration of GSK1278863

Part 2: Cmax, EPO Following Administration of GSK1278863

Part 2: Number of Participants With Abnormal Urinalysis Findings

Part 2: Number of Participants With AEs and SAEs

Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline

Part 2: Tmax, EPO Following Administration of GSK1278863