Trial Outcomes & Findings for Effects of GSK2798745 on Alveolar Barrier Disruption in a Segmental Lipopolysaccharide (LPS) Challenge Model (NCT NCT03511105)
NCT ID: NCT03511105
Last Updated: 2021-03-29
Results Overview
Participants underwent segmental challenge to lungs, via bronchoscopy, at 2 hours after first dose of investigational medicinal product. BAL samples were taken, via bronchoscopy and total protein was measured. Baseline (2 hours) samples were taken immediately before the LPS and saline challenges, from a segment in the left lower lobe, and post-challenge samples were taken at 24 hours (26 hours post-first dose) after the LPS and saline challenges, from the challenged segments. Evaluable Population consists of all participants for whom results of the primary analysis can be determined i.e. all randomized participants who received two correct doses of study treatment, received LPS and saline segmental challenge (in contralateral lobes) and for which results of both baseline (2 hours) and LPS lobe (26 hours) BAL samples are evaluable. This population will be based on treatment the participant actually received. Median and 95% credible interval (CrI) has been presented.
TERMINATED
PHASE1
47 participants
Baseline and at 26 hours post-first dose
2021-03-29
Participant Flow
This was a randomized, placebo-controlled, parallel group, double-blind (sponsor-open), segmental lipopolysaccharide (LPS) challenge study of GSK2798745 in healthy participants.
A total of 47 participants were randomized in the study. The study was terminated due to low probability of achieving a positive outcome on the primary endpoint.
Participant milestones
| Measure |
Placebo
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
22
|
|
Overall Study
COMPLETED
|
23
|
22
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Withdrew consent
|
1
|
0
|
Baseline Characteristics
Effects of GSK2798745 on Alveolar Barrier Disruption in a Segmental Lipopolysaccharide (LPS) Challenge Model
Baseline characteristics by cohort
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.4 Years
STANDARD_DEVIATION 5.07 • n=5 Participants
|
27.1 Years
STANDARD_DEVIATION 6.02 • n=7 Participants
|
26.7 Years
STANDARD_DEVIATION 5.48 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
25 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and at 26 hours post-first dosePopulation: Evaluable Population.
Participants underwent segmental challenge to lungs, via bronchoscopy, at 2 hours after first dose of investigational medicinal product. BAL samples were taken, via bronchoscopy and total protein was measured. Baseline (2 hours) samples were taken immediately before the LPS and saline challenges, from a segment in the left lower lobe, and post-challenge samples were taken at 24 hours (26 hours post-first dose) after the LPS and saline challenges, from the challenged segments. Evaluable Population consists of all participants for whom results of the primary analysis can be determined i.e. all randomized participants who received two correct doses of study treatment, received LPS and saline segmental challenge (in contralateral lobes) and for which results of both baseline (2 hours) and LPS lobe (26 hours) BAL samples are evaluable. This population will be based on treatment the participant actually received. Median and 95% credible interval (CrI) has been presented.
Outcome measures
| Measure |
Placebo
n=23 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Baseline Adjusted Total Protein Concentration in Broncho-alveolar (BAL) Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose)
|
348.46 Milligrams per liter
Interval 285.97 to 425.67
|
318.43 Milligrams per liter
Interval 260.18 to 389.98
|
SECONDARY outcome
Timeframe: Baseline and at 26 hours post-first dosePopulation: Evaluable Population.
Participants underwent segmental challenge to the lungs, via bronchoscopy, at 2 hours (Baseline) after the first dose of investigational medicinal product. BAL samples were taken, via bronchoscopy and total neutrophil cell count was measured. Baseline samples were taken immediately before the LPS and saline challenges, from a segment in the left lower lobe, and post-challenge samples were taken at 24 hours (26 hours post-first dose) after the LPS and saline challenges, from the challenged segments. Median and 95% CrI at indicated time point has been presented.
Outcome measures
| Measure |
Placebo
n=23 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Baseline Adjusted Total Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose)
|
58.94 10^6 cells per milliliter
Interval 42.7 to 81.42
|
54.63 10^6 cells per milliliter
Interval 39.21 to 75.9
|
SECONDARY outcome
Timeframe: Baseline and at 26 hours post-first dosePopulation: Evaluable Population.
Participants underwent segmental challenge to the lungs, via bronchoscopy, at 2 hours after the first dose of investigational medicinal product. BAL samples were taken, via bronchoscopy and total neutrophil cell count was measured. Baseline samples were taken immediately before the LPS and saline challenges, from a segment in the left lower lobe, and post-challenge samples were taken at 24 hour (26 hours post-first dose) after the LPS and saline challenges, from the challenged segments. Median and 95% CrI at the indicated time point has been presented.
Outcome measures
| Measure |
Placebo
n=23 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Baseline Adjusted Differential Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose)
|
58.57 Percentage of total cell count
Interval 54.37 to 63.09
|
58.54 Percentage of total cell count
Interval 54.22 to 63.12
|
SECONDARY outcome
Timeframe: Up to Day 9 (FU/EW)Population: All Subjects Population.
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect and other important medical events. All Subjects Population consists of all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant actually received. SAEs and non-SAEs were analyzed up to follow-up or early withdrawal (FU/EW) of Day 9.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs
Any SAE
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs
Any non-SAE
|
10 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphate (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine kinase (CK). Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameters
ALP, Day 2
|
1.64 International units per liter
Standard Deviation 8.144
|
4.00 International units per liter
Standard Deviation 7.578
|
|
Change From Baseline Values for Clinical Chemistry Parameters
ALP, Day 9
|
-3.20 International units per liter
Standard Deviation 7.953
|
-1.86 International units per liter
Standard Deviation 6.198
|
|
Change From Baseline Values for Clinical Chemistry Parameters
ALT, Day 2
|
1.2 International units per liter
Standard Deviation 16.87
|
-3.5 International units per liter
Standard Deviation 3.08
|
|
Change From Baseline Values for Clinical Chemistry Parameters
ALT, Day 9
|
4.4 International units per liter
Standard Deviation 26.94
|
-2.6 International units per liter
Standard Deviation 5.14
|
|
Change From Baseline Values for Clinical Chemistry Parameters
AST, Day 2
|
18.4 International units per liter
Standard Deviation 109.78
|
-2.3 International units per liter
Standard Deviation 3.97
|
|
Change From Baseline Values for Clinical Chemistry Parameters
AST, Day 9
|
-0.2 International units per liter
Standard Deviation 10.79
|
-1.7 International units per liter
Standard Deviation 3.83
|
|
Change From Baseline Values for Clinical Chemistry Parameters
CK, Day 2
|
1196.0 International units per liter
Standard Deviation 6333.76
|
-60.9 International units per liter
Standard Deviation 59.96
|
|
Change From Baseline Values for Clinical Chemistry Parameters
CK, Day 9
|
-239.2 International units per liter
Standard Deviation 1091.86
|
-37.5 International units per liter
Standard Deviation 75.43
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of clinical chemistry parameters direct bilirubin, total bilirubin and creatinine. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Direct bilirubin, Day 2
|
0.8824 Micromoles per liter
Standard Deviation 0.72998
|
0.8939 Micromoles per liter
Standard Deviation 0.78261
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Direct bilirubin, Day 9
|
0.3010 Micromoles per liter
Standard Deviation 0.85966
|
0.3187 Micromoles per liter
Standard Deviation 1.07930
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Total bilirubin, Day 2
|
3.7552 Micromoles per liter
Standard Deviation 3.91607
|
4.2284 Micromoles per liter
Standard Deviation 4.96144
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Total bilirubin, Day 9
|
0.0616 Micromoles per liter
Standard Deviation 5.13211
|
1.1115 Micromoles per liter
Standard Deviation 6.29042
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Creatinine, Day 2
|
-4.7029 Micromoles per liter
Standard Deviation 8.78354
|
-6.4291 Micromoles per liter
Standard Deviation 8.07523
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Creatinine, Day 9
|
-4.6322 Micromoles per liter
Standard Deviation 9.99897
|
-4.6611 Micromoles per liter
Standard Deviation 7.82718
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium, sodium and urea/BUN. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Calcium, Day 2
|
-0.052 Millimoles per liter
Standard Deviation 0.0653
|
-0.051 Millimoles per liter
Standard Deviation 0.1052
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Calcium, Day 9
|
-0.009 Millimoles per liter
Standard Deviation 0.0888
|
0.020 Millimoles per liter
Standard Deviation 0.0794
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Glucose, Day 2
|
1.12130 Millimoles per liter
Standard Deviation 1.787201
|
0.77714 Millimoles per liter
Standard Deviation 1.785548
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Glucose, Day 9
|
-0.10214 Millimoles per liter
Standard Deviation 0.834757
|
0.06813 Millimoles per liter
Standard Deviation 0.814014
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Potassium, Day 2
|
-0.530 Millimoles per liter
Standard Deviation 0.4884
|
-0.445 Millimoles per liter
Standard Deviation 0.4781
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Potassium, Day 9
|
-0.039 Millimoles per liter
Standard Deviation 0.4104
|
0.085 Millimoles per liter
Standard Deviation 0.2389
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Sodium, Day 2
|
0.6 Millimoles per liter
Standard Deviation 2.14
|
0.9 Millimoles per liter
Standard Deviation 2.14
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Sodium, Day 9
|
0.2 Millimoles per liter
Standard Deviation 1.82
|
-0.3 Millimoles per liter
Standard Deviation 2.10
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Urea, Day 2
|
-1.1710 Millimoles per liter
Standard Deviation 1.36145
|
-0.8114 Millimoles per liter
Standard Deviation 1.10273
|
|
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Urea, Day 9
|
-0.3142 Millimoles per liter
Standard Deviation 1.22512
|
-0.6978 Millimoles per liter
Standard Deviation 1.21927
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of clinical chemistry parameter- CRP. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP)
Day 2
|
10.98 Milligrams per liter
Standard Deviation 7.330
|
13.25 Milligrams per liter
Standard Deviation 9.186
|
|
Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP)
Day 9
|
1.40 Milligrams per liter
Standard Deviation 2.505
|
0.92 Milligrams per liter
Standard Deviation 1.825
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9Population: All Subjects Population.
Blood samples were collected for the analysis of clinical chemistry parameter- total protein. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Clinical Chemistry Parameter-Total Protein
Day 2
|
-0.6 Grams per liter
Standard Deviation 3.50
|
0.7 Grams per liter
Standard Deviation 5.35
|
|
Change From Baseline Values for Clinical Chemistry Parameter-Total Protein
Day 9
|
-0.6 Grams per liter
Standard Deviation 4.20
|
1.0 Grams per liter
Standard Deviation 4.57
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameters
Basophils, Day 2
|
-0.02 Giga cells per liter
Standard Deviation 0.050
|
-0.01 Giga cells per liter
Standard Deviation 0.035
|
|
Change From Baseline Values for Hematology Parameters
Basophils, Day 9
|
-0.01 Giga cells per liter
Standard Deviation 0.053
|
0.00 Giga cells per liter
Standard Deviation 0.044
|
|
Change From Baseline Values for Hematology Parameters
Eosinophils, Day 2
|
-0.01 Giga cells per liter
Standard Deviation 0.067
|
-0.05 Giga cells per liter
Standard Deviation 0.118
|
|
Change From Baseline Values for Hematology Parameters
Eosinophils, Day 9
|
0.01 Giga cells per liter
Standard Deviation 0.108
|
-0.05 Giga cells per liter
Standard Deviation 0.106
|
|
Change From Baseline Values for Hematology Parameters
Lymphocytes, Day 2
|
-0.67 Giga cells per liter
Standard Deviation 0.542
|
-0.40 Giga cells per liter
Standard Deviation 0.359
|
|
Change From Baseline Values for Hematology Parameters
Lymphocytes, Day 9
|
-0.48 Giga cells per liter
Standard Deviation 0.471
|
0.71 Giga cells per liter
Standard Deviation 4.949
|
|
Change From Baseline Values for Hematology Parameters
Monocytes, Day 2
|
-0.04 Giga cells per liter
Standard Deviation 0.250
|
0.04 Giga cells per liter
Standard Deviation 0.176
|
|
Change From Baseline Values for Hematology Parameters
Monocytes, Day 9
|
-0.04 Giga cells per liter
Standard Deviation 0.142
|
-0.12 Giga cells per liter
Standard Deviation 0.123
|
|
Change From Baseline Values for Hematology Parameters
Neutrophils, Day 2
|
1.18 Giga cells per liter
Standard Deviation 2.346
|
1.89 Giga cells per liter
Standard Deviation 3.083
|
|
Change From Baseline Values for Hematology Parameters
Neutrophils, Day 9
|
-0.94 Giga cells per liter
Standard Deviation 1.943
|
-1.14 Giga cells per liter
Standard Deviation 2.418
|
|
Change From Baseline Values for Hematology Parameters
Platelet count, Day 2
|
-16.6 Giga cells per liter
Standard Deviation 17.63
|
-15.0 Giga cells per liter
Standard Deviation 23.63
|
|
Change From Baseline Values for Hematology Parameters
Platelet count, Day 9
|
6.2 Giga cells per liter
Standard Deviation 24.19
|
21.1 Giga cells per liter
Standard Deviation 22.29
|
|
Change From Baseline Values for Hematology Parameters
WBC count, Day 2
|
0.42 Giga cells per liter
Standard Deviation 2.323
|
1.50 Giga cells per liter
Standard Deviation 3.071
|
|
Change From Baseline Values for Hematology Parameters
WBC count, Day 9
|
-1.46 Giga cells per liter
Standard Deviation 1.999
|
-1.65 Giga cells per liter
Standard Deviation 2.371
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Hemoglobin
Day 2
|
0.1 Grams per liter
Standard Deviation 6.88
|
1.5 Grams per liter
Standard Deviation 7.25
|
|
Change From Baseline Values for Hematology Parameter: Hemoglobin
Day 9
|
-3.4 Grams per liter
Standard Deviation 6.39
|
-3.6 Grams per liter
Standard Deviation 5.70
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of hematology parameters: hematocrit and reticulocytes. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes
Hematocrit, Day 2
|
-0.015 Percentage of red blood cells in blood
Standard Deviation 0.0228
|
-0.010 Percentage of red blood cells in blood
Standard Deviation 0.0213
|
|
Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes
Hematocrit, Day 9
|
-0.025 Percentage of red blood cells in blood
Standard Deviation 0.0237
|
-0.027 Percentage of red blood cells in blood
Standard Deviation 0.0167
|
|
Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes
Reticulocytes, Day 2
|
-0.0000 Percentage of red blood cells in blood
Standard Deviation 0.00162
|
-0.0002 Percentage of red blood cells in blood
Standard Deviation 0.00150
|
|
Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes
Reticulocytes, Day 9
|
0.0022 Percentage of red blood cells in blood
Standard Deviation 0.00227
|
0.0013 Percentage of red blood cells in blood
Standard Deviation 0.00247
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of hematology parameter: MCH. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH)
Day 2
|
0.04 Picograms
Standard Deviation 0.300
|
0.10 Picograms
Standard Deviation 0.312
|
|
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH)
Day 9
|
-0.02 Picograms
Standard Deviation 0.335
|
0.06 Picograms
Standard Deviation 0.357
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of hematology parameter: MCV. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV)
Day 2
|
-2.83 Femtoliters
Standard Deviation 2.755
|
-2.59 Femtoliters
Standard Deviation 1.478
|
|
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV)
Day 9
|
-2.93 Femtoliters
Standard Deviation 2.313
|
-3.15 Femtoliters
Standard Deviation 1.760
|
SECONDARY outcome
Timeframe: Baseline (Day -1)and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Blood samples were collected for the analysis of hematology parameter: RBC count. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count
Day 2
|
-0.004 Tera cells per liter
Standard Deviation 0.2382
|
0.038 Tera cells per liter
Standard Deviation 0.2524
|
|
Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count
Day 9
|
-0.118 Tera cells per liter
Standard Deviation 0.2221
|
-0.128 Tera cells per liter
Standard Deviation 0.1929
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
Day 2
|
-0.3 pH
Standard Deviation 1.21
|
0.0 pH
Standard Deviation 1.20
|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
Day 9
|
-0.4 pH
Standard Deviation 1.12
|
0.2 pH
Standard Deviation 1.19
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)Population: All Subjects Population.
Urine samples were collected for the analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The dipstick test gives results in a semi-quantitative manner. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline in Urine Specific Gravity
Day 2
|
-0.0010 Ratio
Standard Deviation 0.00946
|
0.0016 Ratio
Standard Deviation 0.00836
|
|
Change From Baseline in Urine Specific Gravity
Day 9
|
-0.0004 Ratio
Standard Deviation 0.00721
|
-0.0041 Ratio
Standard Deviation 0.00908
|
SECONDARY outcome
Timeframe: Up to Day 9 (FU/EW)Population: All Subjects Population.
A single 12-lead ECG was performed at the specified timepoints during the study where the participant was instructed to be in semi-recumbent position for 5 minutes before obtaining the ECG. An ECG machine that automatically calculated the heart rate and measures like the PR, QRS, QT, and corrected QT intervals. Number of participants with worst-case post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. The decision if an ECG abnormality is clinically significant or not-clinically significant was in the discretion of the investigator, based on her/his clinical judgement. Baseline values is defined as the latest pre-treatment assessment with a non-missing value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings
Abnormal-not clinically significant
|
21 Participants
|
20 Participants
|
|
Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings
Abnormal-clinically significant
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 9 (FU/EW)Population: Safety Population. This analysis was not planned and data was not collected and captured in the database.
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight were also measured and recorded. A brief physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (Day -1) and at 1, 6, 12, 14, 30 hours and Day 9 (FU/EW)Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
The DBP and SBP were measured in participants in a semi-supine position after 5 minutes rest. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP, 1 hour, n=25, 22
|
1.34 Millimeters of mercury
Standard Deviation 4.945
|
-1.34 Millimeters of mercury
Standard Deviation 4.568
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP, 6 hours, n=25, 22
|
2.46 Millimeters of mercury
Standard Deviation 5.006
|
4.25 Millimeters of mercury
Standard Deviation 5.642
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP, 12 hours, n=25, 22
|
3.70 Millimeters of mercury
Standard Deviation 4.409
|
-0.07 Millimeters of mercury
Standard Deviation 7.053
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP, 14 hours, n=24, 22
|
2.77 Millimeters of mercury
Standard Deviation 6.694
|
0.43 Millimeters of mercury
Standard Deviation 6.225
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP, 30 hours, n=25, 22
|
1.86 Millimeters of mercury
Standard Deviation 5.088
|
1.75 Millimeters of mercury
Standard Deviation 5.026
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP, Day 9, n=25, 22
|
-0.06 Millimeters of mercury
Standard Deviation 6.009
|
-0.70 Millimeters of mercury
Standard Deviation 5.719
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP, 1 hour, n=25, 22
|
-1.20 Millimeters of mercury
Standard Deviation 6.722
|
1.07 Millimeters of mercury
Standard Deviation 8.839
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP, 6 hours, n=25, 22
|
6.92 Millimeters of mercury
Standard Deviation 6.372
|
7.30 Millimeters of mercury
Standard Deviation 7.428
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP, 12 hours, n=25, 22
|
8.64 Millimeters of mercury
Standard Deviation 5.959
|
5.66 Millimeters of mercury
Standard Deviation 9.713
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP, 14 hours, n=24, 22
|
8.35 Millimeters of mercury
Standard Deviation 8.098
|
4.84 Millimeters of mercury
Standard Deviation 7.078
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP, 30 hours, n=25, 22
|
7.20 Millimeters of mercury
Standard Deviation 5.681
|
5.02 Millimeters of mercury
Standard Deviation 9.380
|
|
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP, Day 9, n=25, 22
|
2.48 Millimeters of mercury
Standard Deviation 7.913
|
-0.98 Millimeters of mercury
Standard Deviation 8.574
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at 1, 6, 12, 14, 30 hours and Day 9 (FU/EW)Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Heart rate was measured at indicated time points in supine position after 5 minutes rest for the participants. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline in Heart Rate
1 hour, n=25, 22
|
-3.28 Beats per minute
Standard Deviation 7.666
|
-3.61 Beats per minute
Standard Deviation 11.640
|
|
Change From Baseline in Heart Rate
6 hours, n=25, 22
|
13.12 Beats per minute
Standard Deviation 8.402
|
11.75 Beats per minute
Standard Deviation 11.732
|
|
Change From Baseline in Heart Rate
12 hours, n=25, 22
|
14.56 Beats per minute
Standard Deviation 11.438
|
11.89 Beats per minute
Standard Deviation 13.917
|
|
Change From Baseline in Heart Rate
14 hours, n=24, 22
|
14.00 Beats per minute
Standard Deviation 13.808
|
11.84 Beats per minute
Standard Deviation 14.937
|
|
Change From Baseline in Heart Rate
30 hours, n=25, 22
|
14.40 Beats per minute
Standard Deviation 11.183
|
17.02 Beats per minute
Standard Deviation 10.239
|
|
Change From Baseline in Heart Rate
Day 9, n=25, 22
|
1.44 Beats per minute
Standard Deviation 8.885
|
-1.02 Beats per minute
Standard Deviation 9.749
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and at 1, 2, 6, 8, 12, 14, 30 hours and Day 9 (FU/EW)Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Temperature was measured at indicated time points in supine position after 5 minutes rest for the participants. Baseline values were defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Change From Baseline in Temperature
1 hour, n=25, 22
|
-0.06 Degree celsius
Standard Deviation 0.380
|
0.01 Degree celsius
Standard Deviation 0.256
|
|
Change From Baseline in Temperature
2 hours, n=25, 22
|
-0.22 Degree celsius
Standard Deviation 0.485
|
-0.06 Degree celsius
Standard Deviation 0.362
|
|
Change From Baseline in Temperature
6 hours, n=25, 22
|
0.09 Degree celsius
Standard Deviation 0.411
|
0.07 Degree celsius
Standard Deviation 0.400
|
|
Change From Baseline in Temperature
8 hours, n=25, 22
|
0.12 Degree celsius
Standard Deviation 0.473
|
0.21 Degree celsius
Standard Deviation 0.537
|
|
Change From Baseline in Temperature
12 hours, n=25, 22
|
0.65 Degree celsius
Standard Deviation 0.395
|
0.74 Degree celsius
Standard Deviation 0.735
|
|
Change From Baseline in Temperature
14 hours, n=24, 22
|
0.63 Degree celsius
Standard Deviation 0.523
|
0.84 Degree celsius
Standard Deviation 0.764
|
|
Change From Baseline in Temperature
30 hours, n=25, 22
|
0.10 Degree celsius
Standard Deviation 0.434
|
0.26 Degree celsius
Standard Deviation 0.286
|
|
Change From Baseline in Temperature
Day 9, n=25, 22
|
-0.20 Degree celsius
Standard Deviation 0.612
|
-0.11 Degree celsius
Standard Deviation 0.803
|
SECONDARY outcome
Timeframe: At Day 9Population: All Subjects Population.
Based on the preclinical finding of gastric erosions, FOBT was performed before and after dosing at screening and follow-up and any positive hemoglobin measurement was recorded as potentially clinically important. Participants with at least one recorded result has been reported.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Number of Participants With Positive Fecal Occult Blood Test (FOBT) Data
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) pre-bronchodilator and at Day 1 (pre-bronchodilator and 6 Hours), at Day 2 (25.5 and 30 Hours) and Day 9 pre-bronchodilatorPopulation: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Spirometric assessments including FEV1 and FVC were conducted from screening and up to Day 9. Measurements were made in triplicate and the highest FEV1 and FVC were recorded in the case report form (CRF). Mean FEV1 and FVC values along with 95% confidence interval (CI) at indicated timepoints has been presented. Baseline values is defined as the latest pre-treatment assessment with a non-missing value.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 Participants
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FEV1, Day 1, Pre-bronchodilator, n=25, 22
|
4.651 Liters
Interval 4.352 to 4.95
|
4.744 Liters
Interval 4.491 to 4.997
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FEV1, Day 1, 6 Hours, n=25, 22
|
4.564 Liters
Interval 4.268 to 4.86
|
4.658 Liters
Interval 4.396 to 4.92
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FEV1, Day 2, 25.5 Hours, n=23, 22
|
4.496 Liters
Interval 4.233 to 4.759
|
4.704 Liters
Interval 4.433 to 4.975
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FEV1, Day 2, 30 Hours, n=23, 22
|
4.419 Liters
Interval 4.147 to 4.691
|
4.617 Liters
Interval 4.326 to 4.909
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FEV1, Day 9, pre-bronchodilator, n=25, 22
|
4.640 Liters
Interval 4.346 to 4.935
|
4.796 Liters
Interval 4.517 to 5.075
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FVC, Day 1, Pre-bronchodilator, n=25, 22
|
5.834 Liters
Interval 5.516 to 6.153
|
5.867 Liters
Interval 5.544 to 6.19
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FVC, Day 1, 6 Hours, n=25, 22
|
5.647 Liters
Interval 5.316 to 5.978
|
5.711 Liters
Interval 5.372 to 6.051
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FVC, Day 2, 25.5 Hours, n=23, 22
|
5.699 Liters
Interval 5.392 to 6.006
|
5.820 Liters
Interval 5.467 to 6.172
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FVC, Day 2, 30 Hours, n=23, 22
|
5.497 Liters
Interval 5.189 to 5.806
|
5.642 Liters
Interval 5.281 to 6.002
|
|
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
FVC, Day 9, pre-bronchodilator, n=25, 22
|
5.769 Liters
Interval 5.453 to 6.085
|
5.863 Liters
Interval 5.513 to 6.214
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 6, 8, 12, 12.5, 13, 13.5, 14, 15, 24 and 26 hours post-dosePopulation: PK Population.
Blood samples were collected at indicated time points. The 2 and 26-hour blood samples were taken immediately before BAL sampling. Pharmacokinetic (PK) Population consists of all participants in the All Subjects Population who had at least one non-missing PK assessment (Non-quantifiable \[NQ\] values will be considered as non-missing values).
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Area Under the Curve During 26 Hours of GSK2798745
|
221.27 Hour*nanograms per milliliter
Geometric Coefficient of Variation 20.8
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 6, 8, 12, 12.5, 13, 13.5, 14, 15, 24 and 26 hours post-dosePopulation: PK Population.
Blood samples were collected at indicated time points. The 2- and 26-hour blood samples were taken immediately before BAL sampling.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of GSK2798745
|
14.821 Nanograms per milliliter
Geometric Coefficient of Variation 17.7
|
—
|
Adverse Events
Placebo
GSK2798745
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=25 participants at risk
Participants received two tablets of placebo in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of placebo was administered 10 hours after LPS and saline challenge.
|
GSK2798745
n=22 participants at risk
Participants received two tablets of 2.4 milligrams (mg) GSK2798745 in the morning on Day 1. Participants then underwent segmental challenge at 2 hours after first dose wherein LPS was instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of a single tablet of 2.4 mg GSK2798745 was administered 10 hours after LPS and saline challenge.
|
|---|---|---|
|
Nervous system disorders
Headache
|
20.0%
5/25 • Number of events 5 • SAEs and non-SAEs were collected up to Day 9.
SAEs and non-SAEs were summarized for All Subjects Population
|
18.2%
4/22 • Number of events 4 • SAEs and non-SAEs were collected up to Day 9.
SAEs and non-SAEs were summarized for All Subjects Population
|
|
General disorders
Pyrexia
|
12.0%
3/25 • Number of events 3 • SAEs and non-SAEs were collected up to Day 9.
SAEs and non-SAEs were summarized for All Subjects Population
|
18.2%
4/22 • Number of events 5 • SAEs and non-SAEs were collected up to Day 9.
SAEs and non-SAEs were summarized for All Subjects Population
|
|
Infections and infestations
Nasopharyngitis
|
12.0%
3/25 • Number of events 3 • SAEs and non-SAEs were collected up to Day 9.
SAEs and non-SAEs were summarized for All Subjects Population
|
0.00%
0/22 • SAEs and non-SAEs were collected up to Day 9.
SAEs and non-SAEs were summarized for All Subjects Population
|
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