Trial Outcomes & Findings for Daprodustat Hepatic Impairment Study (NCT NCT03223337)
NCT ID: NCT03223337
Last Updated: 2019-09-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
37 participants
Primary outcome timeframe
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
Results posted on
2019-09-04
Participant Flow
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).
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.
Participant milestones
| Measure |
Part 1: Moderate Hepatic Impairment Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
Part 2: Mild Hepatic Impairment Participants
Participants with mild hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during part 2 of the study. This group included at least one participant with a Child-Pugh score of 5 and 6 for mild hepatic impairment.
|
Part 2: Healthy Participants
Healthy control participants, matched to mild hepatic impairment participants in gender, age and BMI received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state in part 2 of the study.
|
|---|---|---|---|---|
|
Part 1 (Up to 16 Days)
STARTED
|
8
|
8
|
0
|
0
|
|
Part 1 (Up to 16 Days)
COMPLETED
|
8
|
8
|
0
|
0
|
|
Part 1 (Up to 16 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Part 2 (Up to 16 Days)
STARTED
|
0
|
0
|
12
|
9
|
|
Part 2 (Up to 16 Days)
COMPLETED
|
0
|
0
|
12
|
9
|
|
Part 2 (Up to 16 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Daprodustat Hepatic Impairment Study
Baseline characteristics by cohort
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
Part 2: Mild Hepatic Impairment Participants
n=12 Participants
Participants with mild hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during part 2 of the study. This group included at least one participant with a Child-Pugh score of 5 and 6 for mild hepatic impairment.
|
Part 2: Healthy Participants
n=9 Participants
Healthy control participants, matched to mild hepatic impairment participants in gender, age and BMI received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state in part 2 of the study.
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
59.5 Years
STANDARD_DEVIATION 6.00 • n=5 Participants
|
57.6 Years
STANDARD_DEVIATION 7.15 • n=7 Participants
|
61.9 Years
STANDARD_DEVIATION 7.55 • n=5 Participants
|
58.7 Years
STANDARD_DEVIATION 8.03 • n=4 Participants
|
59.7 Years
STANDARD_DEVIATION 7.18 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
BLACK OR AFRICAN AMERICAN
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
ASIAN - EAST ASIAN HERITAGE
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
WHITE - ARABIC/NORTH AFRICAN HERITAGE
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK1278863
|
296.2407 Hour*nanogram per milliliter
Geometric Coefficient of Variation 111.1
|
148.3225 Hour*nanogram per milliliter
Geometric Coefficient of Variation 31.7
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
77.6352 Hour*nanogram per milliliter
Geometric Coefficient of Variation 56.9
|
47.1340 Hour*nanogram per milliliter
Geometric Coefficient of Variation 30.9
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
47.5557 Hour*nanogram per milliliter
Geometric Coefficient of Variation 67.4
|
28.9896 Hour*nanogram per milliliter
Geometric Coefficient of Variation 30.3
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
16.8212 Hour*nanogram per milliliter
Geometric Coefficient of Variation 43.9
|
11.2658 Hour*nanogram per milliliter
Geometric Coefficient of Variation 29.4
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
NA Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
NA Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
33.9398 Hour*nanogram per milliliter
Geometric Coefficient of Variation 49.2
|
20.9224 Hour*nanogram per milliliter
Geometric Coefficient of Variation 27.7
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
52.0606 Hour*nanogram per milliliter
Geometric Coefficient of Variation 34.0
|
39.6044 Hour*nanogram per milliliter
Geometric Coefficient of Variation 32.1
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=7 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK1278863
|
299.8773 Hour*nanogram per milliliter
Geometric Coefficient of Variation 39.9
|
205.7559 Hour*nanogram per milliliter
Geometric Coefficient of Variation 37.2
|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
91.3799 Hour*nanogram per milliliter
Geometric Coefficient of Variation 44.7
|
47.1647 Hour*nanogram per milliliter
Geometric Coefficient of Variation 26.9
|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
63.6211 Hour*nanogram per milliliter
Geometric Coefficient of Variation 40.1
|
31.7637 Hour*nanogram per milliliter
Geometric Coefficient of Variation 28.4
|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
19.4020 Hour*nanogram per milliliter
Geometric Coefficient of Variation 36.6
|
11.3374 Hour*nanogram per milliliter
Geometric Coefficient of Variation 26.7
|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
91.7692 Hour*nanogram per milliliter
Geometric Coefficient of Variation 41.0
|
50.1154 Hour*nanogram per milliliter
Geometric Coefficient of Variation 28.3
|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
41.4666 Hour*nanogram per milliliter
Geometric Coefficient of Variation 31.2
|
21.0066 Hour*nanogram per milliliter
Geometric Coefficient of Variation 23.5
|
|
Part 2: AUC (0-infinity) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
46.7001 Hour*nanogram per milliliter
Geometric Coefficient of Variation 66.5
|
31.9797 Hour*nanogram per milliliter
Geometric Coefficient of Variation 40.9
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK1278863
|
0.0463 Percentage of AUCex
Standard Deviation 0.03971
|
0.0486 Percentage of AUCex
Standard Deviation 0.03445
|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
0.1919 Percentage of AUCex
Standard Deviation 0.14164
|
0.4176 Percentage of AUCex
Standard Deviation 0.38893
|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
0.5756 Percentage of AUCex
Standard Deviation 0.89564
|
0.6763 Percentage of AUCex
Standard Deviation 0.61031
|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
0.6147 Percentage of AUCex
Standard Deviation 0.17403
|
2.1559 Percentage of AUCex
Standard Deviation 2.01781
|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
NA Percentage of AUCex
Standard Deviation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
NA Percentage of AUCex
Standard Deviation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
0.2598 Percentage of AUCex
Standard Deviation 0.10004
|
0.3689 Percentage of AUCex
Standard Deviation 0.26189
|
|
Part 1: Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
0.2983 Percentage of AUCex
Standard Deviation 0.27141
|
0.2787 Percentage of AUCex
Standard Deviation 0.15617
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=7 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK1278863
|
0.1148 Percentage of AUCex
Standard Deviation 0.26035
|
0.0601 Percentage of AUCex
Standard Deviation 0.06032
|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
0.2943 Percentage of AUCex
Standard Deviation 0.32698
|
0.8105 Percentage of AUCex
Standard Deviation 1.60084
|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
0.2584 Percentage of AUCex
Standard Deviation 0.30727
|
0.9054 Percentage of AUCex
Standard Deviation 0.89147
|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
0.5138 Percentage of AUCex
Standard Deviation 0.22859
|
1.5924 Percentage of AUCex
Standard Deviation 1.69300
|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
0.2565 Percentage of AUCex
Standard Deviation 0.28382
|
0.6875 Percentage of AUCex
Standard Deviation 1.33005
|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
0.2915 Percentage of AUCex
Standard Deviation 0.25350
|
0.9412 Percentage of AUCex
Standard Deviation 0.94415
|
|
Part 2: Percentage AUCex of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
0.2327 Percentage of AUCex
Standard Deviation 0.23338
|
0.5256 Percentage of AUCex
Standard Deviation 0.46352
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK1278863
|
296.1035 Hour*nanogram per milliliter
Geometric Coefficient of Variation 111.2
|
148.2504 Hour*nanogram per milliliter
Geometric Coefficient of Variation 31.8
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
77.4861 Hour*nanogram per milliliter
Geometric Coefficient of Variation 57.0
|
46.9368 Hour*nanogram per milliliter
Geometric Coefficient of Variation 31.0
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
47.2803 Hour*nanogram per milliliter
Geometric Coefficient of Variation 67.7
|
28.7930 Hour*nanogram per milliliter
Geometric Coefficient of Variation 30.6
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
16.7177 Hour*nanogram per milliliter
Geometric Coefficient of Variation 43.9
|
11.0208 Hour*nanogram per milliliter
Geometric Coefficient of Variation 30.9
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
NA Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
NA Hour*nanogram per milliliter
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
33.8516 Hour*nanogram per milliliter
Geometric Coefficient of Variation 49.3
|
20.8451 Hour*nanogram per milliliter
Geometric Coefficient of Variation 27.8
|
|
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
51.9052 Hour*nanogram per milliliter
Geometric Coefficient of Variation 34.1
|
39.4939 Hour*nanogram per milliliter
Geometric Coefficient of Variation 32.3
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=7 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK1278863
|
299.5322 Hour*nanogram per milliliter
Geometric Coefficient of Variation 39.9
|
205.6322 Hour*nanogram per milliliter
Geometric Coefficient of Variation 37.2
|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
91.1105 Hour*nanogram per milliliter
Geometric Coefficient of Variation 44.9
|
46.7771 Hour*nanogram per milliliter
Geometric Coefficient of Variation 27.9
|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
63.4564 Hour*nanogram per milliliter
Geometric Coefficient of Variation 40.3
|
31.4750 Hour*nanogram per milliliter
Geometric Coefficient of Variation 29.0
|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
19.3023 Hour*nanogram per milliliter
Geometric Coefficient of Variation 36.8
|
11.1555 Hour*nanogram per milliliter
Geometric Coefficient of Variation 27.1
|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
91.5334 Hour*nanogram per milliliter
Geometric Coefficient of Variation 41.2
|
49.7669 Hour*nanogram per milliliter
Geometric Coefficient of Variation 29.2
|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
41.3456 Hour*nanogram per milliliter
Geometric Coefficient of Variation 31.4
|
20.8080 Hour*nanogram per milliliter
Geometric Coefficient of Variation 24.0
|
|
Part 2: AUC (0-t) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
46.5914 Hour*nanogram per milliliter
Geometric Coefficient of Variation 66.8
|
31.8113 Hour*nanogram per milliliter
Geometric Coefficient of Variation 41.3
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK1278863
|
139.705 Nanogram per milliliter
Geometric Coefficient of Variation 108.8
|
70.607 Nanogram per milliliter
Geometric Coefficient of Variation 51.7
|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
13.046 Nanogram per milliliter
Geometric Coefficient of Variation 46.2
|
10.199 Nanogram per milliliter
Geometric Coefficient of Variation 28.7
|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
10.022 Nanogram per milliliter
Geometric Coefficient of Variation 55.0
|
8.025 Nanogram per milliliter
Geometric Coefficient of Variation 28.5
|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
2.650 Nanogram per milliliter
Geometric Coefficient of Variation 34.6
|
2.245 Nanogram per milliliter
Geometric Coefficient of Variation 23.0
|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
5.946 Nanogram per milliliter
Geometric Coefficient of Variation 41.7
|
4.672 Nanogram per milliliter
Geometric Coefficient of Variation 24.1
|
|
Part 1: Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
7.411 Nanogram per milliliter
Geometric Coefficient of Variation 35.0
|
7.120 Nanogram per milliliter
Geometric Coefficient of Variation 28.0
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=7 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK1278863
|
113.232 Nanogram per milliliter
Geometric Coefficient of Variation 42.6
|
112.142 Nanogram per milliliter
Geometric Coefficient of Variation 35.7
|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK2391220 (M2)
|
15.792 Nanogram per milliliter
Geometric Coefficient of Variation 40.8
|
8.846 Nanogram per milliliter
Geometric Coefficient of Variation 40.0
|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK2487818 (M4)
|
13.614 Nanogram per milliliter
Geometric Coefficient of Variation 34.7
|
7.723 Nanogram per milliliter
Geometric Coefficient of Variation 35.6
|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK2506102 (M5)
|
3.241 Nanogram per milliliter
Geometric Coefficient of Variation 35.7
|
1.975 Nanogram per milliliter
Geometric Coefficient of Variation 33.4
|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK2506104 (M3)
|
15.475 Nanogram per milliliter
Geometric Coefficient of Variation 38.8
|
8.926 Nanogram per milliliter
Geometric Coefficient of Variation 37.9
|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK2531398 (M6)
|
7.333 Nanogram per milliliter
Geometric Coefficient of Variation 28.2
|
4.010 Nanogram per milliliter
Geometric Coefficient of Variation 31.7
|
|
Part 2: Cmax of GSK1278863 and Its Metabolites.
GSK2531401 (M13)
|
6.791 Nanogram per milliliter
Geometric Coefficient of Variation 65.5
|
5.081 Nanogram per milliliter
Geometric Coefficient of Variation 43.4
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK1278863
|
3.9867 Hours
Geometric Coefficient of Variation 33.2
|
4.4054 Hours
Geometric Coefficient of Variation 29.8
|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
4.1830 Hours
Geometric Coefficient of Variation 26.9
|
5.6415 Hours
Geometric Coefficient of Variation 37.1
|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
2.6559 Hours
Geometric Coefficient of Variation 38.3
|
3.6385 Hours
Geometric Coefficient of Variation 83.8
|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
3.1966 Hours
Geometric Coefficient of Variation 23.4
|
2.7314 Hours
Geometric Coefficient of Variation 36.4
|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
NA Hours
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
NA Hours
Geometric Coefficient of Variation NA
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
3.1287 Hours
Geometric Coefficient of Variation 26.0
|
3.2641 Hours
Geometric Coefficient of Variation 56.3
|
|
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
3.9432 Hours
Geometric Coefficient of Variation 22.8
|
3.9414 Hours
Geometric Coefficient of Variation 33.1
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=7 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK1278863
|
4.5251 Hours
Geometric Coefficient of Variation 27.4
|
4.2792 Hours
Geometric Coefficient of Variation 38.7
|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
4.8118 Hours
Geometric Coefficient of Variation 21.2
|
4.7439 Hours
Geometric Coefficient of Variation 49.6
|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
4.1059 Hours
Geometric Coefficient of Variation 47.8
|
3.0578 Hours
Geometric Coefficient of Variation 88.9
|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
3.4087 Hours
Geometric Coefficient of Variation 30.8
|
3.3108 Hours
Geometric Coefficient of Variation 56.7
|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
4.6675 Hours
Geometric Coefficient of Variation 20.2
|
4.4967 Hours
Geometric Coefficient of Variation 45.0
|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
3.8096 Hours
Geometric Coefficient of Variation 38.4
|
2.9947 Hours
Geometric Coefficient of Variation 57.1
|
|
Part 2: T1/2 of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
4.2869 Hours
Geometric Coefficient of Variation 21.2
|
3.5510 Hours
Geometric Coefficient of Variation 34.2
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK1278863
|
1.50 Hours
Interval 1.0 to 3.0
|
2.00 Hours
Interval 1.0 to 3.0
|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
3.00 Hours
Interval 3.0 to 6.0
|
3.50 Hours
Interval 2.0 to 4.0
|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
3.00 Hours
Interval 2.0 to 6.0
|
3.00 Hours
Interval 1.5 to 4.0
|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
3.50 Hours
Interval 3.0 to 6.0
|
4.00 Hours
Interval 2.0 to 4.0
|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
NA Hours
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
NA Hours
Data was not calculable for the metabolite GSK2506104 (M3) due to matrix-related suppression during the bio-analysis of the Part 1 pharmacokinetic plasma samples.
|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
3.50 Hours
Interval 3.0 to 6.0
|
3.50 Hours
Interval 2.0 to 4.0
|
|
Part 1: Time of Occurrence of Cmax (Tmax) of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
4.00 Hours
Interval 3.0 to 6.0
|
4.00 Hours
Interval 3.0 to 6.0
|
PRIMARY outcome
Timeframe: 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-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=7 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK1278863
|
1.50 Hours
Interval 1.0 to 3.0
|
1.50 Hours
Interval 1.0 to 4.0
|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK2391220 (M2)
|
3.00 Hours
Interval 3.0 to 4.0
|
3.00 Hours
Interval 2.0 to 4.0
|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK2487818 (M4)
|
3.00 Hours
Interval 2.0 to 4.0
|
3.00 Hours
Interval 2.0 to 4.0
|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK2506102 (M5)
|
3.50 Hours
Interval 3.0 to 4.0
|
3.00 Hours
Interval 2.0 to 6.0
|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK2506104 (M3)
|
3.50 Hours
Interval 3.0 to 4.0
|
3.00 Hours
Interval 2.0 to 6.0
|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK2531398 (M6)
|
3.00 Hours
Interval 3.0 to 4.0
|
3.00 Hours
Interval 2.0 to 6.0
|
|
Part 2: Tmax of GSK1278863 and Its Metabolites
GSK2531401 (M13)
|
4.00 Hours
Interval 3.0 to 4.0
|
4.00 Hours
Interval 3.0 to 6.0
|
PRIMARY outcome
Timeframe: 3 hours, 12 hours and 24 hours post-dosePopulation: Pharmacokinetic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 3 hours
|
0.27989 Nanograms per milliliter
Standard Deviation 0.261668
|
0.11076 Nanograms per milliliter
Standard Deviation 0.070114
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 12 hours
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 24 hours
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 3 hours
|
4.47750 Nanograms per milliliter
Standard Deviation 1.779468
|
2.85875 Nanograms per milliliter
Standard Deviation 1.129961
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 12 hours
|
0.76525 Nanograms per milliliter
Standard Deviation 0.656087
|
0.22463 Nanograms per milliliter
Standard Deviation 0.119826
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 24 hours
|
0.06460 Nanograms per milliliter
Standard Deviation 0.089209
|
0.00963 Nanograms per milliliter
Standard Deviation 0.017963
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 3 hours
|
3.24463 Nanograms per milliliter
Standard Deviation 1.506964
|
1.86813 Nanograms per milliliter
Standard Deviation 0.760479
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 12 hours
|
0.29301 Nanograms per milliliter
Standard Deviation 0.338773
|
0.04769 Nanograms per milliliter
Standard Deviation 0.031411
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 24 hours
|
0.01201 Nanograms per milliliter
Standard Deviation 0.023617
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 3 hours
|
0.64588 Nanograms per milliliter
Standard Deviation 0.242321
|
0.43175 Nanograms per milliliter
Standard Deviation 0.165059
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 12 hours
|
0.13024 Nanograms per milliliter
Standard Deviation 0.109089
|
0.04143 Nanograms per milliliter
Standard Deviation 0.031140
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 24 hours
|
0.00923 Nanograms per milliliter
Standard Deviation 0.026092
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 3 hours
|
3.86250 Nanograms per milliliter
Standard Deviation 1.402241
|
2.57000 Nanograms per milliliter
Standard Deviation 1.010262
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 12 hours
|
0.71075 Nanograms per milliliter
Standard Deviation 0.601452
|
0.23938 Nanograms per milliliter
Standard Deviation 0.121781
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 24 hours
|
0.06315 Nanograms per milliliter
Standard Deviation 0.104994
|
0.00829 Nanograms per milliliter
Standard Deviation 0.015374
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 3 hours
|
1.42725 Nanograms per milliliter
Standard Deviation 0.552287
|
0.89338 Nanograms per milliliter
Standard Deviation 0.334179
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 12 hours
|
0.22973 Nanograms per milliliter
Standard Deviation 0.199514
|
0.06548 Nanograms per milliliter
Standard Deviation 0.035504
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 24 hours
|
0.01470 Nanograms per milliliter
Standard Deviation 0.028580
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 3 hours
|
2.25375 Nanograms per milliliter
Standard Deviation 0.646771
|
2.03738 Nanograms per milliliter
Standard Deviation 0.807331
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 12 hours
|
0.63125 Nanograms per milliliter
Standard Deviation 0.379804
|
0.32075 Nanograms per milliliter
Standard Deviation 0.163981
|
|
Part 1: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 24 hours
|
0.07580 Nanograms per milliliter
Standard Deviation 0.110738
|
0.01053 Nanograms per milliliter
Standard Deviation 0.020023
|
PRIMARY outcome
Timeframe: 3 hours, 12 hours and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 12 hours; n=8,7
|
0.25856 Nanograms per milliliter
Standard Deviation 0.425759
|
0.04796 Nanograms per milliliter
Standard Deviation 0.035510
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 3 hours; n=6, 6
|
1.24213 Nanograms per milliliter
Standard Deviation 2.475347
|
0.15692 Nanograms per milliliter
Standard Deviation 0.138726
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 12 hours; n=7, 6
|
0.04343 Nanograms per milliliter
Standard Deviation 0.114901
|
0.01527 Nanograms per milliliter
Standard Deviation 0.037396
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 24 hours; n=7, 6
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 3 hours; n=8, 7
|
5.32625 Nanograms per milliliter
Standard Deviation 2.139472
|
2.13700 Nanograms per milliliter
Standard Deviation 1.276959
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 12 hours; n=8, 7
|
0.81263 Nanograms per milliliter
Standard Deviation 0.600031
|
0.24371 Nanograms per milliliter
Standard Deviation 0.079803
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 24 hours; n=8, 7
|
0.30654 Nanograms per milliliter
Standard Deviation 0.729605
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 3 hours; n=8,7
|
3.91375 Nanograms per milliliter
Standard Deviation 1.441219
|
1.57633 Nanograms per milliliter
Standard Deviation 0.937244
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 12 hours; n=8,7
|
0.40141 Nanograms per milliliter
Standard Deviation 0.560638
|
0.07793 Nanograms per milliliter
Standard Deviation 0.033300
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 24 hours; n=8,7
|
0.00839 Nanograms per milliliter
Standard Deviation 0.015586
|
0.00454 Nanograms per milliliter
Standard Deviation 0.012019
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 3 hours; n=8,7
|
0.78213 Nanograms per milliliter
Standard Deviation 0.314177
|
0.31091 Nanograms per milliliter
Standard Deviation 0.213793
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 24 hours; n=8,7
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 3 hours; n=8,7
|
4.68625 Nanograms per milliliter
Standard Deviation 1.839883
|
1.94271 Nanograms per milliliter
Standard Deviation 1.262970
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 12 hours; n=8,7
|
0.75350 Nanograms per milliliter
Standard Deviation 0.496638
|
0.27014 Nanograms per milliliter
Standard Deviation 0.122830
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 24 hours; n=8,7
|
0.04093 Nanograms per milliliter
Standard Deviation 0.029445
|
0.00819 Nanograms per milliliter
Standard Deviation 0.021657
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 3 hours; n=8,7
|
1.86763 Nanograms per milliliter
Standard Deviation 0.713958
|
0.73530 Nanograms per milliliter
Standard Deviation 0.451869
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 12 hours; n=8,7
|
0.34200 Nanograms per milliliter
Standard Deviation 0.412505
|
0.07879 Nanograms per milliliter
Standard Deviation 0.023474
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 24 hours; n=8,7
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Nanograms per milliliter
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 3 hours; n=8,7
|
2.47825 Nanograms per milliliter
Standard Deviation 0.965944
|
1.26771 Nanograms per milliliter
Standard Deviation 0.871839
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 12 hours; n=8,7
|
0.75363 Nanograms per milliliter
Standard Deviation 0.597207
|
0.29429 Nanograms per milliliter
Standard Deviation 0.153615
|
|
Part 2: Unbound Concentration in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 24 hours; n=8,7
|
0.29830 Nanograms per milliliter
Standard Deviation 0.720919
|
0.00454 Nanograms per milliliter
Standard Deviation 0.012019
|
PRIMARY outcome
Timeframe: 3 hours, 12 hours and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 3 hours; n=8, 8
|
0.0034 Percentage of unbound drug in plasma
Standard Deviation 0.00109
|
0.0028 Percentage of unbound drug in plasma
Standard Deviation 0.00019
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 12 hours; n=8, 8
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 24 hours; n=8,8
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 3 hours; n=8,8
|
0.3379 Percentage of unbound drug in plasma
Standard Deviation 0.03573
|
0.3495 Percentage of unbound drug in plasma
Standard Deviation 0.05135
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 12 hours; n=8,8
|
0.3540 Percentage of unbound drug in plasma
Standard Deviation 0.02186
|
0.3355 Percentage of unbound drug in plasma
Standard Deviation 0.02172
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 24 hours; n=4,2
|
0.3861 Percentage of unbound drug in plasma
Standard Deviation 0.02827
|
0.3902 Percentage of unbound drug in plasma
Standard Deviation 0.07149
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 3 hours; n=8,8
|
0.3080 Percentage of unbound drug in plasma
Standard Deviation 0.03085
|
0.2925 Percentage of unbound drug in plasma
Standard Deviation 0.01981
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 12 hours; n=8,7
|
0.3071 Percentage of unbound drug in plasma
Standard Deviation 0.03419
|
0.2402 Percentage of unbound drug in plasma
Standard Deviation 0.02431
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 24 hours; n=2,8
|
0.3508 Percentage of unbound drug in plasma
Standard Deviation 0.00191
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 3 hours; n=8, 8
|
0.2565 Percentage of unbound drug in plasma
Standard Deviation 0.04573
|
0.2441 Percentage of unbound drug in plasma
Standard Deviation 0.03397
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 12 hours; n=8, 6
|
0.2517 Percentage of unbound drug in plasma
Standard Deviation 0.04022
|
0.2335 Percentage of unbound drug in plasma
Standard Deviation 0.02679
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 24 hours; n=1, 8
|
0.2723 Percentage of unbound drug in plasma
Standard Deviation NA
Data was not available as standard deviation could not be calculated for single participant.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 3 hours; n=8, 8
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 12 hours; n=8, 8
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 24 hours; n=8, 8
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 3 hours; n=8, 8
|
0.2469 Percentage of unbound drug in plasma
Standard Deviation 0.04315
|
0.2461 Percentage of unbound drug in plasma
Standard Deviation 0.03264
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 12 hours; n=8, 8
|
0.2550 Percentage of unbound drug in plasma
Standard Deviation 0.03166
|
0.2295 Percentage of unbound drug in plasma
Standard Deviation 0.01509
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 24 hours; n=2, 8
|
0.3005 Percentage of unbound drug in plasma
Standard Deviation 0.03734
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 3 hours; n=8, 8
|
0.3519 Percentage of unbound drug in plasma
Standard Deviation 0.04431
|
0.3844 Percentage of unbound drug in plasma
Standard Deviation 0.06838
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 12 hours; n=8, 8
|
0.3771 Percentage of unbound drug in plasma
Standard Deviation 0.02114
|
0.3565 Percentage of unbound drug in plasma
Standard Deviation 0.02558
|
|
Part 1: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 24 hours; n=6, 2
|
0.3817 Percentage of unbound drug in plasma
Standard Deviation 0.04449
|
0.3716 Percentage of unbound drug in plasma
Standard Deviation 0.02411
|
PRIMARY outcome
Timeframe: 3 hours, 12 hours and 24 hours post-dosePopulation: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 3 hours; n=8, 7
|
0.2762 Percentage of unbound drug in plasma
Standard Deviation 0.02792
|
0.2857 Percentage of unbound drug in plasma
Standard Deviation 0.03897
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 3 hours; n=6, 6
|
0.0134 Percentage of unbound drug in plasma
Standard Deviation 0.02369
|
0.0032 Percentage of unbound drug in plasma
Standard Deviation 0.00090
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 12 hours; n=1, 1
|
0.1231 Percentage of unbound drug in plasma
Standard Deviation NA
Data was not available as standard deviation could not be calculated for single participant..
|
0.1246 Percentage of unbound drug in plasma
Standard Deviation NA
Data was not available as standard deviation could not be calculated for single participant..
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK1278863; 24 hours; n=8,7
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 3 hours; n=8, 7
|
0.3191 Percentage of unbound drug in plasma
Standard Deviation 0.02263
|
0.3343 Percentage of unbound drug in plasma
Standard Deviation 0.06101
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 12 hours; n=7, 7
|
0.3305 Percentage of unbound drug in plasma
Standard Deviation 0.03497
|
0.3174 Percentage of unbound drug in plasma
Standard Deviation 0.02174
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2391220 (M2); 24 hours; n=5, 7
|
0.4099 Percentage of unbound drug in plasma
Standard Deviation 0.04797
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 12 hours; n=7, 7
|
0.2850 Percentage of unbound drug in plasma
Standard Deviation 0.03110
|
0.2766 Percentage of unbound drug in plasma
Standard Deviation 0.03608
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2487818 (M4); 24 hours; n=2, 1
|
0.3116 Percentage of unbound drug in plasma
Standard Deviation 0.07106
|
0.3387 Percentage of unbound drug in plasma
Standard Deviation NA
Data was not available as standard deviation could not be calculated for single participant.
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 3 hours; n=8, 6
|
0.2339 Percentage of unbound drug in plasma
Standard Deviation 0.02704
|
0.2171 Percentage of unbound drug in plasma
Standard Deviation 0.06728
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 12 hours; n=7, 6
|
0.2483 Percentage of unbound drug in plasma
Standard Deviation 0.03166
|
0.2191 Percentage of unbound drug in plasma
Standard Deviation 0.02903
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506102 (M5); 24 hours; n=8, 7
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 3 hours; n=8, 7
|
0.2904 Percentage of unbound drug in plasma
Standard Deviation 0.02480
|
0.2938 Percentage of unbound drug in plasma
Standard Deviation 0.02618
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 12 hours; n=7, 7
|
0.2970 Percentage of unbound drug in plasma
Standard Deviation 0.02959
|
0.2845 Percentage of unbound drug in plasma
Standard Deviation 0.02193
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2506104 (M3); 24 hours; n=6, 1
|
0.3267 Percentage of unbound drug in plasma
Standard Deviation 0.03171
|
0.3016 Percentage of unbound drug in plasma
Standard Deviation NA
Data was not available as standard deviation could not be calculated for single participant.
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 3 hours; n=8, 7
|
0.2491 Percentage of unbound drug in plasma
Standard Deviation 0.02989
|
0.2444 Percentage of unbound drug in plasma
Standard Deviation 0.04833
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 12 hours; n=7, 7
|
0.2500 Percentage of unbound drug in plasma
Standard Deviation 0.03259
|
0.2346 Percentage of unbound drug in plasma
Standard Deviation 0.02031
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531398 (M6); 24 hours; n=8, 7
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
NA Percentage of unbound drug in plasma
Standard Deviation NA
Mean and Standard Deviation were not calculable because concentration values were below detectable levels, but were imputed in the analysis.
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 3 hours; n=8, 7
|
0.3595 Percentage of unbound drug in plasma
Standard Deviation 0.02324
|
0.3569 Percentage of unbound drug in plasma
Standard Deviation 0.03504
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 12 hours; n=7, 7
|
0.3527 Percentage of unbound drug in plasma
Standard Deviation 0.03957
|
0.3386 Percentage of unbound drug in plasma
Standard Deviation 0.01580
|
|
Part 2: Unbound Fraction in Plasma of GSK1278863 and Its Metabolites
GSK2531401 (M13); 24 hours; n=5, 1
|
0.4154 Percentage of unbound drug in plasma
Standard Deviation 0.03151
|
0.3845 Percentage of unbound drug in plasma
Standard Deviation NA
Data was not available as standard deviation could not be calculated for single participant.
|
SECONDARY outcome
Timeframe: 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-dosePopulation: Pharmacodynamic Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Maximum Observed Erythropoietin Concentration (Cmax, EPO) Following Administration of GSK1278863
|
48.898 International units per liter
Standard Deviation 36.8476
|
28.391 International units per liter
Standard Deviation 13.1904
|
SECONDARY outcome
Timeframe: 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-dosePopulation: Pharmacodynamic Population
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Cmax, EPO Following Administration of GSK1278863
|
43.933 International units per liter
Standard Deviation 20.2602
|
45.871 International units per liter
Standard Deviation 35.1537
|
SECONDARY outcome
Timeframe: 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-dosePopulation: Pharmacodynamic Population
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Time of the Maximum Observed Erythropoietin Concentration (Tmax, EPO) Following Administration of GSK1278863
|
10.0 Hours
Interval 8.0 to 12.0
|
10.0 Hours
Interval 8.0 to 10.0
|
SECONDARY outcome
Timeframe: 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-dosePopulation: Pharmacodynamic Population
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Tmax, EPO Following Administration of GSK1278863
|
10.0 Hours
Interval 0.0 to 48.0
|
10.0 Hours
Interval 6.0 to 12.0
|
SECONDARY outcome
Timeframe: 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-dosePopulation: Pharmacodynamic Population
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Erythropoietin Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t, EPO]) Following Administration of GSK1278863
|
1262.3724 Hours* International units per liter
Standard Deviation 1148.34702
|
697.7140 Hours* International units per liter
Standard Deviation 393.05978
|
SECONDARY outcome
Timeframe: 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-dosePopulation: Pharmacodynamic Population
Venous blood samples were collected for measurement of plasma EPO at the indicated time points following administration of GSK1278863.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: AUC (0-t, EPO) Following Administration of GSK1278863
|
1258.6211 Hours* International units per liter
Standard Deviation 683.32848
|
1061.7549 Hours* International units per liter
Standard Deviation 647.67154
|
SECONDARY outcome
Timeframe: Up to 16 daysPopulation: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AE
|
1 Participants
|
2 Participants
|
|
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 16 daysPopulation: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Number of Participants With AEs and SAEs
Any SAE
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With AEs and SAEs
Any AE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Screening) and up to Day 16Population: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Hematocrit; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Hematocrit; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Hematocrit; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Hemoglobin; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Hemoglobin; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Hemoglobin; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Leukocytes; To Low
|
1 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Leukocytes; To within Range or No Change
|
7 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Leukocytes; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Lymphocytes; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Lymphocytes; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Lymphocytes; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Neutrophils; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Neutrophils; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Neutrophils; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Platelets; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Platelets; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Hematology Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Platelets; To High
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Screening) and up to Day 16Population: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Hematocrit; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Hematocrit; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Hematocrit; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Hemoglobin; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Hemoglobin; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Hemoglobin; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Leukocytes; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Leukocytes; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Leukocytes; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Lymphocytes; To Low
|
1 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Lymphocytes; To within Range or No Change
|
11 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Lymphocytes; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Neutrophils; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Neutrophils; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Neutrophils; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Platelets; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Platelets; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Platelets; To High
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Screening) and up to Day 16Population: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Bilirubin; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
ALT ; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
ALT;To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
ALT; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Albumin; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Albumin; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Albumin; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Alkaline Phosphatase; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Alkaline Phosphatase; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Alkaline Phosphatase; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
AST; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
AST;To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
AST; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Bilirubin; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Bilirubin; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Calcium; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Calcium; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Calcium; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Glucose; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Glucose; To within Range or No Change
|
6 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Glucose; To High
|
2 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Potassium; To Low
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Potassium; To within Range or No Change
|
8 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Potassium; To High
|
0 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Sodium; To Low
|
1 Participants
|
0 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Sodium; To within Range or No Change
|
7 Participants
|
8 Participants
|
|
Part 1: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Sodium; To High
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Screening) and up to Day 16Population: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
ALT ; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
ALT;To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
ALT ; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Albumin; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Albumin; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Albumin; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Alkaline Phosphatase; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Alkaline Phosphatase; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Alkaline Phosphatase; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
AST; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
AST;To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
AST; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Bilirubin; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Bilirubin; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Bilirubin; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Calcium; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Calcium; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Calcium; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Glucose; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Glucose; To within Range or No Change
|
10 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Glucose; To High
|
2 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Potassium; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Potassium; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Potassium; To High
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Sodium; To Low
|
0 Participants
|
0 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Sodium; To within Range or No Change
|
12 Participants
|
9 Participants
|
|
Part 2: Number of Participants With Worst Case Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Sodium; To High
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 16Population: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=8 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 1: Number of Participants With Abnormal Urinalysis Findings
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 16Population: Safety Population
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.
Outcome measures
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=12 Participants
Participants with moderate hepatic impairment received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state during Part 1 of the study. This group included at least one participant with a Child-Pugh score of 7, 8 and 9 for moderate hepatic impairment.
|
Part 1: Healthy Participants
n=9 Participants
Healthy control participants, matched to moderate hepatic impairment participants in gender, age and Body mass index (BMI) received 6 mg of GSK1278863 as a single oral dose tablet in the fasted state.
|
|---|---|---|
|
Part 2: Number of Participants With Abnormal Urinalysis Findings
|
0 Participants
|
0 Participants
|
Adverse Events
Part 1: Moderate Hepatic Impairment Participants
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Part 1: Healthy Participants
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part 2: Mild Hepatic Impairment Participants
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Part 2: Healthy Participants
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part 1: Moderate Hepatic Impairment Participants
n=8 participants at risk
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.
|
Part 1: Healthy Participants
n=8 participants at risk
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.
|
Part 2: Mild Hepatic Impairment Participants
n=12 participants at risk
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.
|
Part 2: Healthy Participants
n=9 participants at risk
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.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/8 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
12.5%
1/8 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/12 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/9 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/8 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
12.5%
1/8 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/12 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/9 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
12.5%
1/8 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/12 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/9 • 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.
SAEs and Non-SAEs were reported for Safety Population comprised of all participants who received at least one dose of study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER