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Daprodustat Hepatic Impairment Study

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT03223337
Collaborator
(none)
37
Enrollment
2
Locations
4
Arms
12.9
Actual Duration (Months)
18.5
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Daprodustat (GSK1278863)
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
37 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
All subjects will receive 6 mg of daprodustat as a single oral dose in parallel way throughout the study period.All subjects will receive 6 mg of daprodustat as a single oral dose in parallel way throughout the study period.
Masking:
None (Open Label)
Masking Description:
This will be an open-label study and no blinding will be performed.
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jul 24, 2017
Actual Primary Completion Date :
Aug 20, 2018
Actual Study Completion Date :
Aug 20, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Subjects with moderate hepatic impairment: Part 1

Approximately 8 subjects with moderate hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 7, one with a score of 8 and one with a score of 9. The group will also include at least one female and at least one male subject.

Drug: Daprodustat (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.
Active Comparator: Matched Healthy controls: Part 1

Approximately 8 healthy controls, matched in gender, age and BMI to subjects with moderate hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject.

Drug: Daprodustat (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.
Experimental: Subjects with either mild or severe hepatic impairment: Part 2

Approximately 8 subjects with mild or severe hepatic impairment will receive 6 mg of daprodustat as a single oral dose in the fasted state. This group will include at least one subject with a Child-Pugh score of 5 and one with a score of 6 for mild hepatic impairment and at least one subject with a Child-Pugh score of 10 or 11 and one with a score of 12 or 13 for severe hepatic impairment. The group will also include at least one female and at least one male subject.

Drug: Daprodustat (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.
Active Comparator: Matched healthy controls: Part 2

Approximately 8 healthy controls, matched in gender, age and BMI to subjects with mild or severe hepatic impairment, will receive 6 mg of daprodustat as a single oral dose in the fasted state. The group will include at least one female and at least one male subject.

Drug: Daprodustat (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.

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

Secondary Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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).

Exclusion Criteria:
For all subjects:

  • QT interval corrected for heart rate according to Fridericia's formula (QTcF) >500 milliseconds (msec).

  • Recent history of deep vein thrombosis, pulmonary embolism or other thrombosis related condition. Any prior medical history in these areas will be reviewed and approved by the PI and the sponsor's Medical Monitor on a case by case basis as needed.

  • Myocardial infarction or acute coronary syndrome, stroke or transient ischemic attack within the 12 weeks prior to enrollment.

  • Subjects with a pre-existing condition (other than liver disease) interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of daprodustat.

  • Subjects that have undergone cholecystectomy within the past 3 months.

  • Subjects with chronic inflammatory joint disease (example, scleroderma, systemic lupus erythematosis, rheumatoid arthritis).

  • History of malignancy within the prior 2 years or known kidney mass >3 centimeter (cm) (end stage renal disease subjects with impairment only) OR currently receiving treatment for cancer. ONLY exception is localized squamous cell or basal cell carcinoma of the skin definitively treated 12 weeks prior to enrollment.

  • Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.

  • Current enrolment or past participation (i.e., administration of last dose of investigational study treatment) within the last 30 days (or 5 half-lives, whichever is longer) before Day 1 in this or any other clinical study involving an investigational study treatment or any other type of medical research.

Exclusion criteria for Hepatically-Impaired subjects:

  • Present of 8 times Upper limit of normal (ULN) elevations in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), or bilirubin.

  • Subjects with any other medical condition which, in the judgment of the investigator and Medical Monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject.

  • Subjects with advanced ascites (Grade 3).

  • Subjects with refractory encephalopathy as judged by the investigator or significant Central Nervous System (CNS) disease (example dementia, or seizures) which the investigator considers will interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.

  • Subjects with functional Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.

  • Presence of hepatopulmonary or hepatorenal syndrome.

  • Presence of primarily cholestatic liver diseases.

  • History of liver transplantation.

  • Subjects with signs of active infection, including active spontaneous bacterial peritonitis.

  • Subjects with unstable cardiac function or subjects with hypertension whose blood pressure is not controlled (based on the investigator's discretion).

  • Diabetic subjects whose diabetes is not controlled (based on the investigator's discretion).

Exclusion criteria for healthy control subjects:

  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.

  • Presence of Hepatitis B surface antigen (HBsAg) at screening or Positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study treatment.

  • Positive pre-study drug/alcohol screen.

  • Positive human immunodeficiency virus (HIV) antibody test.

  • Regular use of known drugs of abuse.

  • Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 drinks. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Miami Florida United States 33136
2 GSK Investigational Site Orlando Florida United States 32809

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03223337
Other Study ID Numbers:
  • 200231
First Posted:
Jul 21, 2017
Last Update Posted:
Sep 4, 2019
Last Verified:
Aug 1, 2019
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
GSK1278863
Daprodustat
Healthy control
Single dose
Hepatic Impairment
Additional relevant MeSH terms:
Liver Diseases

Study Results

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 Detail 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.
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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. 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. 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.
Period Title: Part 1 (Up to 16 Days)
STARTED 8 8 0 0
COMPLETED 8 8 0 0
NOT COMPLETED 0 0 0 0
Period Title: Part 1 (Up to 16 Days)
STARTED 0 0 12 9
COMPLETED 0 0 12 9
NOT COMPLETED 0 0 0 0

Baseline Characteristics

Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants Total
Arm/Group Description 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. 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. 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. 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. Total of all reporting groups
Overall Participants 8 8 12 9 37
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
59.5
(6.00)
57.6
(7.15)
61.9
(7.55)
58.7
(8.03)
59.7
(7.18)
Sex: Female, Male (Count of Participants)
Female
1
12.5%
1
12.5%
2
16.7%
2
22.2%
6
16.2%
Male
7
87.5%
7
87.5%
10
83.3%
7
77.8%
31
83.8%
Race/Ethnicity, Customized (Count of Participants)
BLACK OR AFRICAN AMERICAN
0
0%
2
25%
1
8.3%
2
22.2%
5
13.5%
WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE
8
100%
6
75%
6
50%
6
66.7%
26
70.3%
ASIAN - EAST ASIAN HERITAGE
0
0%
0
0%
1
8.3%
0
0%
1
2.7%
WHITE - ARABIC/NORTH AFRICAN HERITAGE
0
0%
0
0%
4
33.3%
1
11.1%
5
13.5%

Outcome Measures

1. Primary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863
296.2407
(111.1)
148.3225
(31.7)
GSK2391220 (M2)
77.6352
(56.9)
47.1340
(30.9)
GSK2487818 (M4)
47.5557
(67.4)
28.9896
(30.3)
GSK2506102 (M5)
16.8212
(43.9)
11.2658
(29.4)
GSK2506104 (M3)
NA
(NA)
NA
(NA)
GSK2531398 (M6)
33.9398
(49.2)
20.9224
(27.7)
GSK2531401 (M13)
52.0606
(34.0)
39.6044
(32.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric Least Square(LS) Mean
Estimated Value 1.9973
Confidence Interval (2-Sided) 90%
1.1063 to 3.6057
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6471
Confidence Interval (2-Sided) 90%
1.1267 to 2.4079
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6404
Confidence Interval (2-Sided) 90%
1.0744 to 2.5048
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.4931
Confidence Interval (2-Sided) 90%
1.0876 to 2.0498
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6222
Confidence Interval (2-Sided) 90%
1.1594 to 2.2696
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.3145
Confidence Interval (2-Sided) 90%
0.9896 to 1.7462
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
2. Primary Outcome
Title Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 7
GSK1278863
299.8773
(39.9)
205.7559
(37.2)
GSK2391220 (M2)
91.3799
(44.7)
47.1647
(26.9)
GSK2487818 (M4)
63.6211
(40.1)
31.7637
(28.4)
GSK2506102 (M5)
19.4020
(36.6)
11.3374
(26.7)
GSK2506104 (M3)
91.7692
(41.0)
50.1154
(28.3)
GSK2531398 (M6)
41.4666
(31.2)
21.0066
(23.5)
GSK2531401 (M13)
46.7001
(66.5)
31.9797
(40.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.4574
Confidence Interval (2-Sided) 90%
1.0350 to 2.0523
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.9375
Confidence Interval (2-Sided) 90%
1.3919 to 2.6968
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.8312
Confidence Interval (2-Sided) 90%
1.3342 to 2.5133
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506104 (M3) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 2.0030
Confidence Interval (2-Sided) 90%
1.4654 to 2.7378
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.7113
Confidence Interval (2-Sided) 90%
1.2818 to 2.2847
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.9740
Confidence Interval (2-Sided) 90%
1.5365 to 2.5360
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.4603
Confidence Interval (2-Sided) 90%
0.9081 to 2.3484
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Mild hepatic impairment participants versus Healthy participants) has been presented.
3. Primary Outcome
Title Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863
0.0463
(0.03971)
0.0486
(0.03445)
GSK2391220 (M2)
0.1919
(0.14164)
0.4176
(0.38893)
GSK2487818 (M4)
0.5756
(0.89564)
0.6763
(0.61031)
GSK2506102 (M5)
0.6147
(0.17403)
2.1559
(2.01781)
GSK2506104 (M3)
NA
(NA)
NA
(NA)
GSK2531398 (M6)
0.2598
(0.10004)
0.3689
(0.26189)
GSK2531401 (M13)
0.2983
(0.27141)
0.2787
(0.15617)
4. Primary Outcome
Title Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 7
GSK1278863
0.1148
(0.26035)
0.0601
(0.06032)
GSK2391220 (M2)
0.2943
(0.32698)
0.8105
(1.60084)
GSK2487818 (M4)
0.2584
(0.30727)
0.9054
(0.89147)
GSK2506102 (M5)
0.5138
(0.22859)
1.5924
(1.69300)
GSK2506104 (M3)
0.2565
(0.28382)
0.6875
(1.33005)
GSK2531398 (M6)
0.2915
(0.25350)
0.9412
(0.94415)
GSK2531401 (M13)
0.2327
(0.23338)
0.5256
(0.46352)
5. Primary Outcome
Title 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
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863
296.1035
(111.2)
148.2504
(31.8)
GSK2391220 (M2)
77.4861
(57.0)
46.9368
(31.0)
GSK2487818 (M4)
47.2803
(67.7)
28.7930
(30.6)
GSK2506102 (M5)
16.7177
(43.9)
11.0208
(30.9)
GSK2506104 (M3)
NA
(NA)
NA
(NA)
GSK2531398 (M6)
33.8516
(49.3)
20.8451
(27.8)
GSK2531401 (M13)
51.9052
(34.1)
39.4939
(32.3)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.9973
Confidence Interval (2-Sided) 90%
1.1061 to 3.6066
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6509
Confidence Interval (2-Sided) 90%
1.1285 to 2.4150
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6421
Confidence Interval (2-Sided) 90%
1.0732 to 2.5125
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.5169
Confidence Interval (2-Sided) 90%
1.0994 to 2.0930
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6240
Confidence Interval (2-Sided) 90%
1.1599 to 2.2736
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.3143
Confidence Interval (2-Sided) 90%
0.9887 to 1.7470
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
6. Primary Outcome
Title Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 7
GSK1278863
299.5322
(39.9)
205.6322
(37.2)
GSK2391220 (M2)
91.1105
(44.9)
46.7771
(27.9)
GSK2487818 (M4)
63.4564
(40.3)
31.4750
(29.0)
GSK2506102 (M5)
19.3023
(36.8)
11.1555
(27.1)
GSK2506104 (M3)
91.5334
(41.2)
49.7669
(29.2)
GSK2531398 (M6)
41.3456
(31.4)
20.8080
(24.0)
GSK2531401 (M13)
46.5914
(66.8)
31.8113
(41.3)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.4566
Confidence Interval (2-Sided) 90%
1.0344 to 2.0513
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.9478
Confidence Interval (2-Sided) 90%
1.3935 to 2.7224
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.8392
Confidence Interval (2-Sided) 90%
1.3350 to 2.5340
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506104 (M3) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 2.0161
Confidence Interval (2-Sided) 90%
1.4711 to 2.7630
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.7303
Confidence Interval (2-Sided) 90%
1.2932 to 2.3151
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.9870
Confidence Interval (2-Sided) 90%
1.5426 to 2.5594
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.4646
Confidence Interval (2-Sided) 90%
0.9086 to 2.3609
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Mild hepatic impairment participants versus Healthy participants) has been presented.
7. Primary Outcome
Title Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863
139.705
(108.8)
70.607
(51.7)
GSK2391220 (M2)
13.046
(46.2)
10.199
(28.7)
GSK2487818 (M4)
10.022
(55.0)
8.025
(28.5)
GSK2506102 (M5)
2.650
(34.6)
2.245
(23.0)
GSK2506104 (M3)
NA
(NA)
NA
(NA)
GSK2531398 (M6)
5.946
(41.7)
4.672
(24.1)
GSK2531401 (M13)
7.411
(35.0)
7.120
(28.0)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.9786
Confidence Interval (2-Sided) 90%
1.0557 to 3.7084
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.2791
Confidence Interval (2-Sided) 90%
0.9241 to 1.7705
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.2487
Confidence Interval (2-Sided) 90%
0.8675 to 1.7974
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.1802
Confidence Interval (2-Sided) 90%
0.9165 to 1.5197
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.2726
Confidence Interval (2-Sided) 90%
0.9520 to 1.7012
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0409
Confidence Interval (2-Sided) 90%
0.7927 to 1.3668
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
8. Primary Outcome
Title Part 2: Cmax of GSK1278863 and Its Metabolites.
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 7
GSK1278863
113.232
(42.6)
112.142
(35.7)
GSK2391220 (M2)
15.792
(40.8)
8.846
(40.0)
GSK2487818 (M4)
13.614
(34.7)
7.723
(35.6)
GSK2506102 (M5)
3.241
(35.7)
1.975
(33.4)
GSK2506104 (M3)
15.475
(38.8)
8.926
(37.9)
GSK2531398 (M6)
7.333
(28.2)
4.010
(31.7)
GSK2531401 (M13)
6.791
(65.5)
5.081
(43.4)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0097
Confidence Interval (2-Sided) 90%
0.7122 to 1.4316
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.7852
Confidence Interval (2-Sided) 90%
1.2498 to 2.5498
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.7337
Confidence Interval (2-Sided) 90%
1.2343 to 2.4353
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506104 (M3) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.7628
Confidence Interval (2-Sided) 90%
1.2898 to 2.4092
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.6413
Confidence Interval (2-Sided) 90%
1.2055 to 2.2347
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.8289
Confidence Interval (2-Sided) 90%
1.3992 to 2.3904
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.3367
Confidence Interval (2-Sided) 90%
0.8288 to 2.1557
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Mild hepatic impairment participants versus Healthy participants) has been presented.
9. Primary Outcome
Title Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863
3.9867
(33.2)
4.4054
(29.8)
GSK2391220 (M2)
4.1830
(26.9)
5.6415
(37.1)
GSK2487818 (M4)
2.6559
(38.3)
3.6385
(83.8)
GSK2506102 (M5)
3.1966
(23.4)
2.7314
(36.4)
GSK2506104 (M3)
NA
(NA)
NA
(NA)
GSK2531398 (M6)
3.1287
(26.0)
3.2641
(56.3)
GSK2531401 (M13)
3.9432
(22.8)
3.9414
(33.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 0.9050
Confidence Interval (2-Sided) 90%
0.6900 to 1.1869
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 0.7415
Confidence Interval (2-Sided) 90%
0.5617 to 0.9787
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 0.7299
Confidence Interval (2-Sided) 90%
0.4387 to 1.2145
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.1703
Confidence Interval (2-Sided) 90%
0.9000 to 1.5219
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 0.9585
Confidence Interval (2-Sided) 90%
0.6664 to 1.3786
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0004
Confidence Interval (2-Sided) 90%
0.7833 to 1.2778
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
10. Primary Outcome
Title Part 2: T1/2 of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 7
GSK1278863
4.5251
(27.4)
4.2792
(38.7)
GSK2391220 (M2)
4.8118
(21.2)
4.7439
(49.6)
GSK2487818 (M4)
4.1059
(47.8)
3.0578
(88.9)
GSK2506102 (M5)
3.4087
(30.8)
3.3108
(56.7)
GSK2506104 (M3)
4.6675
(20.2)
4.4967
(45.0)
GSK2531398 (M6)
3.8096
(38.4)
2.9947
(57.1)
GSK2531401 (M13)
4.2869
(21.2)
3.5510
(34.2)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0574
Confidence Interval (2-Sided) 90%
0.7876 to 1.4197
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK1278863 (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0143
Confidence Interval (2-Sided) 90%
0.7332 to 1.4032
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2391220 (M2) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0380
Confidence Interval (2-Sided) 90%
0.7695 to 1.4002
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506104 (M3) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.3427
Confidence Interval (2-Sided) 90%
0.7635 to 2.3615
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2487818 (M4) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.0296
Confidence Interval (2-Sided) 90%
0.6996 to 1.5151
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2506102 (M5) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.2721
Confidence Interval (2-Sided) 90%
0.8409 to 1.9245
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531398 (M6) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Ratio of Geometric LS Mean
Estimated Value 1.2072
Confidence Interval (2-Sided) 90%
0.9398 to 1.5508
Parameter Dispersion Type:
Value:
Estimation Comments Ratio of Geometric LS Mean for GSK2531401 (M13) (Mild hepatic impairment participants versus Healthy participants) has been presented.
11. Primary Outcome
Title Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863
1.50
2.00
GSK2391220 (M2)
3.00
3.50
GSK2487818 (M4)
3.00
3.00
GSK2506102 (M5)
3.50
4.00
GSK2506104 (M3)
NA
NA
GSK2531398 (M6)
3.50
3.50
GSK2531401 (M13)
4.00
4.00
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.6822
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 0.50
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK1278863 (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5767
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2391220 (M2)(Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5880
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.50
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2487818 (M4)(Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.7716
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2506102 (M5)(Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.4093
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.50
Confidence Interval (2-Sided) 90%
-1.00 to 2.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2531398 (M6) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.9837
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2531401 (M13) (Moderate hepatic impairment participants versus Healthy participants) has been presented.
12. Primary Outcome
Title Part 2: Tmax of GSK1278863 and Its Metabolites
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 7
GSK1278863
1.50
1.50
GSK2391220 (M2)
3.00
3.00
GSK2487818 (M4)
3.00
3.00
GSK2506102 (M5)
3.50
3.00
GSK2506104 (M3)
3.50
3.00
GSK2531398 (M6)
3.00
3.00
GSK2531401 (M13)
4.00
4.00
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.6224
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 0.50
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK1278863 (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8042
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 0.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2391220 (M2) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8423
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2506104 (M3) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5207
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2487818 (M4) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8423
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2506102 (M5) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
-1.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2531398 (M6) (Mild hepatic impairment participants versus Healthy participants) has been presented.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part 1: Moderate Hepatic Impairment Participants, Part 1: Healthy Participants
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8042
Comments P-value was based on Mann-Whitney U test (exact Wilcoxon rank sum test).
Method Wilcoxon (Mann-Whitney)
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 90%
0.00 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments Median Difference in GSK2531401 (M13) (Mild hepatic impairment participants versus Healthy participants) has been presented.
13. Primary Outcome
Title Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
Description 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.
Time Frame 3 hours, 12 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863; 3 hours
0.27989
(0.261668)
0.11076
(0.070114)
GSK1278863; 12 hours
NA
(NA)
NA
(NA)
GSK1278863; 24 hours
NA
(NA)
NA
(NA)
GSK2391220 (M2); 3 hours
4.47750
(1.779468)
2.85875
(1.129961)
GSK2391220 (M2); 12 hours
0.76525
(0.656087)
0.22463
(0.119826)
GSK2391220 (M2); 24 hours
0.06460
(0.089209)
0.00963
(0.017963)
GSK2487818 (M4); 3 hours
3.24463
(1.506964)
1.86813
(0.760479)
GSK2487818 (M4); 12 hours
0.29301
(0.338773)
0.04769
(0.031411)
GSK2487818 (M4); 24 hours
0.01201
(0.023617)
NA
(NA)
GSK2506102 (M5); 3 hours
0.64588
(0.242321)
0.43175
(0.165059)
GSK2506102 (M5); 12 hours
0.13024
(0.109089)
0.04143
(0.031140)
GSK2506102 (M5); 24 hours
0.00923
(0.026092)
NA
(NA)
GSK2506104 (M3); 3 hours
3.86250
(1.402241)
2.57000
(1.010262)
GSK2506104 (M3); 12 hours
0.71075
(0.601452)
0.23938
(0.121781)
GSK2506104 (M3); 24 hours
0.06315
(0.104994)
0.00829
(0.015374)
GSK2531398 (M6); 3 hours
1.42725
(0.552287)
0.89338
(0.334179)
GSK2531398 (M6); 12 hours
0.22973
(0.199514)
0.06548
(0.035504)
GSK2531398 (M6); 24 hours
0.01470
(0.028580)
NA
(NA)
GSK2531401 (M13); 3 hours
2.25375
(0.646771)
2.03738
(0.807331)
GSK2531401 (M13); 12 hours
0.63125
(0.379804)
0.32075
(0.163981)
GSK2531401 (M13); 24 hours
0.07580
(0.110738)
0.01053
(0.020023)
14. Primary Outcome
Title Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
Description 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.
Time Frame 3 hours, 12 hours and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863; 3 hours; n=6, 6
1.24213
(2.475347)
0.15692
(0.138726)
GSK1278863; 12 hours; n=7, 6
0.04343
(0.114901)
0.01527
(0.037396)
GSK1278863; 24 hours; n=7, 6
NA
(NA)
NA
(NA)
GSK2391220 (M2); 3 hours; n=8, 7
5.32625
(2.139472)
2.13700
(1.276959)
GSK2391220 (M2); 12 hours; n=8, 7
0.81263
(0.600031)
0.24371
(0.079803)
GSK2391220 (M2); 24 hours; n=8, 7
0.30654
(0.729605)
NA
(NA)
GSK2487818 (M4); 3 hours; n=8,7
3.91375
(1.441219)
1.57633
(0.937244)
GSK2487818 (M4); 12 hours; n=8,7
0.40141
(0.560638)
0.07793
(0.033300)
GSK2487818 (M4); 24 hours; n=8,7
0.00839
(0.015586)
0.00454
(0.012019)
GSK2506102 (M5); 3 hours; n=8,7
0.78213
(0.314177)
0.31091
(0.213793)
GSK2506102 (M5); 12 hours; n=8,7
0.25856
(0.425759)
0.04796
(0.035510)
GSK2506102 (M5); 24 hours; n=8,7
NA
(NA)
NA
(NA)
GSK2506104 (M3); 3 hours; n=8,7
4.68625
(1.839883)
1.94271
(1.262970)
GSK2506104 (M3); 12 hours; n=8,7
0.75350
(0.496638)
0.27014
(0.122830)
GSK2506104 (M3); 24 hours; n=8,7
0.04093
(0.029445)
0.00819
(0.021657)
GSK2531398 (M6); 3 hours; n=8,7
1.86763
(0.713958)
0.73530
(0.451869)
GSK2531398 (M6); 12 hours; n=8,7
0.34200
(0.412505)
0.07879
(0.023474)
GSK2531398 (M6); 24 hours; n=8,7
NA
(NA)
NA
(NA)
GSK2531401 (M13); 3 hours; n=8,7
2.47825
(0.965944)
1.26771
(0.871839)
GSK2531401 (M13); 12 hours; n=8,7
0.75363
(0.597207)
0.29429
(0.153615)
GSK2531401 (M13); 24 hours; n=8,7
0.29830
(0.720919)
0.00454
(0.012019)
15. Primary Outcome
Title Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863; 3 hours; n=8, 8
0.0034
(0.00109)
0.0028
(0.00019)
GSK1278863; 12 hours; n=8, 8
NA
(NA)
NA
(NA)
GSK1278863; 24 hours; n=8,8
NA
(NA)
NA
(NA)
GSK2391220 (M2); 3 hours; n=8,8
0.3379
(0.03573)
0.3495
(0.05135)
GSK2391220 (M2); 12 hours; n=8,8
0.3540
(0.02186)
0.3355
(0.02172)
GSK2391220 (M2); 24 hours; n=4,2
0.3861
(0.02827)
0.3902
(0.07149)
GSK2487818 (M4); 3 hours; n=8,8
0.3080
(0.03085)
0.2925
(0.01981)
GSK2487818 (M4); 12 hours; n=8,7
0.3071
(0.03419)
0.2402
(0.02431)
GSK2487818 (M4); 24 hours; n=2,8
0.3508
(0.00191)
NA
(NA)
GSK2506102 (M5); 3 hours; n=8, 8
0.2565
(0.04573)
0.2441
(0.03397)
GSK2506102 (M5); 12 hours; n=8, 6
0.2517
(0.04022)
0.2335
(0.02679)
GSK2506102 (M5); 24 hours; n=1, 8
0.2723
(NA)
NA
(NA)
GSK2506104 (M3); 3 hours; n=8, 8
NA
(NA)
NA
(NA)
GSK2506104 (M3); 12 hours; n=8, 8
NA
(NA)
NA
(NA)
GSK2506104 (M3); 24 hours; n=8, 8
NA
(NA)
NA
(NA)
GSK2531398 (M6); 3 hours; n=8, 8
0.2469
(0.04315)
0.2461
(0.03264)
GSK2531398 (M6); 12 hours; n=8, 8
0.2550
(0.03166)
0.2295
(0.01509)
GSK2531398 (M6); 24 hours; n=2, 8
0.3005
(0.03734)
NA
(NA)
GSK2531401 (M13); 3 hours; n=8, 8
0.3519
(0.04431)
0.3844
(0.06838)
GSK2531401 (M13); 12 hours; n=8, 8
0.3771
(0.02114)
0.3565
(0.02558)
GSK2531401 (M13); 24 hours; n=6, 2
0.3817
(0.04449)
0.3716
(0.02411)
16. Primary Outcome
Title Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
GSK1278863; 3 hours; n=6, 6
0.0134
(0.02369)
0.0032
(0.00090)
GSK1278863; 12 hours; n=1, 1
0.1231
(NA)
0.1246
(NA)
GSK1278863; 24 hours; n=8,7
NA
(NA)
NA
(NA)
GSK2391220 (M2); 3 hours; n=8, 7
0.3191
(0.02263)
0.3343
(0.06101)
GSK2391220 (M2); 12 hours; n=7, 7
0.3305
(0.03497)
0.3174
(0.02174)
GSK2391220 (M2); 24 hours; n=5, 7
0.4099
(0.04797)
NA
(NA)
GSK2487818 (M4); 3 hours; n=8, 7
0.2762
(0.02792)
0.2857
(0.03897)
GSK2487818 (M4); 12 hours; n=7, 7
0.2850
(0.03110)
0.2766
(0.03608)
GSK2487818 (M4); 24 hours; n=2, 1
0.3116
(0.07106)
0.3387
(NA)
GSK2506102 (M5); 3 hours; n=8, 6
0.2339
(0.02704)
0.2171
(0.06728)
GSK2506102 (M5); 12 hours; n=7, 6
0.2483
(0.03166)
0.2191
(0.02903)
GSK2506102 (M5); 24 hours; n=8, 7
NA
(NA)
NA
(NA)
GSK2506104 (M3); 3 hours; n=8, 7
0.2904
(0.02480)
0.2938
(0.02618)
GSK2506104 (M3); 12 hours; n=7, 7
0.2970
(0.02959)
0.2845
(0.02193)
GSK2506104 (M3); 24 hours; n=6, 1
0.3267
(0.03171)
0.3016
(NA)
GSK2531398 (M6); 3 hours; n=8, 7
0.2491
(0.02989)
0.2444
(0.04833)
GSK2531398 (M6); 12 hours; n=7, 7
0.2500
(0.03259)
0.2346
(0.02031)
GSK2531398 (M6); 24 hours; n=8, 7
NA
(NA)
NA
(NA)
GSK2531401 (M13); 3 hours; n=8, 7
0.3595
(0.02324)
0.3569
(0.03504)
GSK2531401 (M13); 12 hours; n=7, 7
0.3527
(0.03957)
0.3386
(0.01580)
GSK2531401 (M13); 24 hours; n=5, 1
0.4154
(0.03151)
0.3845
(NA)
17. Secondary Outcome
Title Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacodynamic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
Mean (Standard Deviation) [International units per liter]
48.898
(36.8476)
28.391
(13.1904)
18. Secondary Outcome
Title Part 2: Cmax, EPO Following Administration of GSK1278863
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacodynamic Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
Mean (Standard Deviation) [International units per liter]
43.933
(20.2602)
45.871
(35.1537)
19. Secondary Outcome
Title Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacodynamic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
Median (Full Range) [Hours]
10.0
10.0
20. Secondary Outcome
Title Part 2: Tmax, EPO Following Administration of GSK1278863
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacodynamic Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
Median (Full Range) [Hours]
10.0
10.0
21. Secondary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacodynamic Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
Mean (Standard Deviation) [Hours* International units per liter]
1262.3724
(1148.34702)
697.7140
(393.05978)
22. Secondary Outcome
Title Part 2: AUC (0-t, EPO) Following Administration of GSK1278863
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacodynamic Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
Mean (Standard Deviation) [Hours* International units per liter]
1258.6211
(683.32848)
1061.7549
(647.67154)
23. Secondary Outcome
Title Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
Any SAE
0
0%
0
0%
Any AE
1
12.5%
2
25%
24. Secondary Outcome
Title Part 2: Number of Participants With AEs and SAEs
Description 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.
Time Frame Up to 16 days

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
Any SAE
0
0%
0
0%
Any AE
0
0%
0
0%
25. Secondary Outcome
Title Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
Hematocrit; To Low
0
0%
0
0%
Hematocrit; To within Range or No Change
8
100%
8
100%
Hematocrit; To High
0
0%
0
0%
Hemoglobin; To Low
0
0%
0
0%
Hemoglobin; To within Range or No Change
8
100%
8
100%
Hemoglobin; To High
0
0%
0
0%
Leukocytes; To Low
1
12.5%
0
0%
Leukocytes; To within Range or No Change
7
87.5%
8
100%
Leukocytes; To High
0
0%
0
0%
Lymphocytes; To Low
0
0%
0
0%
Lymphocytes; To within Range or No Change
8
100%
8
100%
Lymphocytes; To High
0
0%
0
0%
Neutrophils; To Low
0
0%
0
0%
Neutrophils; To within Range or No Change
8
100%
8
100%
Neutrophils; To High
0
0%
0
0%
Platelets; To Low
0
0%
0
0%
Platelets; To within Range or No Change
8
100%
8
100%
Platelets; To High
0
0%
0
0%
26. Secondary Outcome
Title Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
Hematocrit; To Low
0
0%
0
0%
Hematocrit; To within Range or No Change
12
150%
9
112.5%
Hematocrit; To High
0
0%
0
0%
Hemoglobin; To Low
0
0%
0
0%
Hemoglobin; To within Range or No Change
12
150%
9
112.5%
Hemoglobin; To High
0
0%
0
0%
Leukocytes; To Low
0
0%
0
0%
Leukocytes; To within Range or No Change
12
150%
9
112.5%
Leukocytes; To High
0
0%
0
0%
Lymphocytes; To Low
1
12.5%
0
0%
Lymphocytes; To within Range or No Change
11
137.5%
9
112.5%
Lymphocytes; To High
0
0%
0
0%
Neutrophils; To Low
0
0%
0
0%
Neutrophils; To within Range or No Change
12
150%
9
112.5%
Neutrophils; To High
0
0%
0
0%
Platelets; To Low
0
0%
0
0%
Platelets; To within Range or No Change
12
150%
9
112.5%
Platelets; To High
0
0%
0
0%
27. Secondary Outcome
Title Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
ALT ; To Low
0
0%
0
0%
ALT;To within Range or No Change
8
100%
8
100%
ALT; To High
0
0%
0
0%
Albumin; To Low
0
0%
0
0%
Albumin; To within Range or No Change
8
100%
8
100%
Albumin; To High
0
0%
0
0%
Alkaline Phosphatase; To Low
0
0%
0
0%
Alkaline Phosphatase; To within Range or No Change
8
100%
8
100%
Alkaline Phosphatase; To High
0
0%
0
0%
AST; To Low
0
0%
0
0%
AST;To within Range or No Change
8
100%
8
100%
AST; To High
0
0%
0
0%
Bilirubin; To Low
0
0%
0
0%
Bilirubin; To within Range or No Change
8
100%
8
100%
Bilirubin; To High
0
0%
0
0%
Calcium; To Low
0
0%
0
0%
Calcium; To within Range or No Change
8
100%
8
100%
Calcium; To High
0
0%
0
0%
Glucose; To Low
0
0%
0
0%
Glucose; To within Range or No Change
6
75%
8
100%
Glucose; To High
2
25%
0
0%
Potassium; To Low
0
0%
0
0%
Potassium; To within Range or No Change
8
100%
8
100%
Potassium; To High
0
0%
0
0%
Sodium; To Low
1
12.5%
0
0%
Sodium; To within Range or No Change
7
87.5%
8
100%
Sodium; To High
0
0%
0
0%
28. Secondary Outcome
Title Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
ALT ; To Low
0
0%
0
0%
ALT;To within Range or No Change
12
150%
9
112.5%
ALT ; To High
0
0%
0
0%
Albumin; To Low
0
0%
0
0%
Albumin; To within Range or No Change
12
150%
9
112.5%
Albumin; To High
0
0%
0
0%
Alkaline Phosphatase; To Low
0
0%
0
0%
Alkaline Phosphatase; To within Range or No Change
12
150%
9
112.5%
Alkaline Phosphatase; To High
0
0%
0
0%
AST; To Low
0
0%
0
0%
AST;To within Range or No Change
12
150%
9
112.5%
AST; To High
0
0%
0
0%
Bilirubin; To Low
0
0%
0
0%
Bilirubin; To within Range or No Change
12
150%
9
112.5%
Bilirubin; To High
0
0%
0
0%
Calcium; To Low
0
0%
0
0%
Calcium; To within Range or No Change
12
150%
9
112.5%
Calcium; To High
0
0%
0
0%
Glucose; To Low
0
0%
0
0%
Glucose; To within Range or No Change
10
125%
9
112.5%
Glucose; To High
2
25%
0
0%
Potassium; To Low
0
0%
0
0%
Potassium; To within Range or No Change
12
150%
9
112.5%
Potassium; To High
0
0%
0
0%
Sodium; To Low
0
0%
0
0%
Sodium; To within Range or No Change
12
150%
9
112.5%
Sodium; To High
0
0%
0
0%
29. Secondary Outcome
Title Part 1: Number of Participants With Abnormal Urinalysis Findings
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 8 8
Count of Participants [Participants]
0
0%
0
0%
30. Secondary Outcome
Title Part 2: Number of Participants With Abnormal Urinalysis Findings
Description 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

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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.
Measure Participants 12 9
Count of Participants [Participants]
0
0%
0
0%

Adverse Events

Time Frame Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to 16 days in each part of the study.
Adverse Event Reporting Description SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
Arm/Group Title Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Arm/Group Description 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. 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. 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. 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.
All Cause Mortality
Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/8 (0%) 0/8 (0%) 0/12 (0%) 0/9 (0%)
Serious Adverse Events
Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/8 (0%) 0/8 (0%) 0/12 (0%) 0/9 (0%)
Other (Not Including Serious) Adverse Events
Part 1: Moderate Hepatic Impairment Participants Part 1: Healthy Participants Part 2: Mild Hepatic Impairment Participants Part 2: Healthy Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/8 (12.5%) 2/8 (25%) 0/12 (0%) 0/9 (0%)
Gastrointestinal disorders
Toothache 0/8 (0%) 1/8 (12.5%) 0/12 (0%) 0/9 (0%)
Infections and infestations
Upper respiratory tract infection 0/8 (0%) 1/8 (12.5%) 0/12 (0%) 0/9 (0%)
Injury, poisoning and procedural complications
Skin abrasion 1/8 (12.5%) 0/8 (0%) 0/12 (0%) 0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email GSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03223337
Other Study ID Numbers:
  • 200231
First Posted:
Jul 21, 2017
Last Update Posted:
Sep 4, 2019
Last Verified:
Aug 1, 2019