Healthy Volunteers
Conditions
Keywords
Lipopolysaccharide, Pharmacodynamics, Healthy subjects, GSK2798745, Placebo, Segmental challenge
Brief summary
The primary objective of the study is to investigate the effect of GSK2798745 on alveolar-septal barrier permeability following LPS challenge in healthy subjects. The influx of protein-rich fluid into the lung due to damage to the alveolar capillary barrier, with resultant adverse effects on respiratory function, is a fundamental underlying defect in Acute Respiratory Distress Syndrome (ARDS). In this Phase 1, proof-of-mechanism study, a LPS challenge will be used as a surrogate injury model to investigate the effects of Transient receptor potential vanilloid 4 (TRPV4) channel blockade on alveolar-septal barrier permeability in man. This is a randomised, placebo-controlled, parallel group, double-blind (sponsor-open), segmental LPS challenge study of GSK2798745 in healthy subjects. Subjects will be randomised in a ratio of 1:1 to take 2 single doses of either 4.8 milligrams GSK2798745 followed by 2.4 milligrams GSK2798745 after 12 hours or a dose of placebo followed by another dose of placebo after 12 hours. The first dose will be administered on Day 1 at 2 hours before Baseline bronchoalveolar lavage (BAL) sampling from a segment in the left lower lobe of lung. LPS 4 nanogram per kilogram will subsequently be instilled into the right middle segment and saline control into the lingula segment of the contralateral side. The second dose of study treatment will be administered 10 hours after LPS challenge followed by post-dose BAL sampling on Day 2. Each subject will take approximately 5 weeks to complete the study.
Interventions
DRUGGSK2798745
GSK2798745 will be available as white to slightly colored, round biconvex tablets to be administered via the oral route.
DRUGPlacebo
Placebo matching to GSK2798745 will be available as white to slightly colored, round biconvex tablet to be administered via the oral route.
DRUGLipoplysaccharide from Escherichia Coli
LPS will be used as challenge agent. About 4 nanogram per kilogram of LPS will be instilled into the right middle lung segment via bronchoscopy 2 hours after dosing with GSK2798745 or placebo on Day 1.
DRUGSaline
Sterile saline (0.9%) will be used as control challenge. Saline will be instilled into the lingula segment of contralateral side of lung via bronchoscopy 2 hours after dosing with GSK2798745 or placebo on Day 1.
Sponsors
Biomedical Advanced Research and Development Authority
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This will be a double blind study where investigator, sub-investigators, other site staff and the subject will be blinded. Selected sponsor study team members will be unblinded to perform the interim analysis. This may include the medical monitor, study statistician, study programmer (and delegates) and study pharmacokineticist.
Intervention model description
This is a randomised, placebo-controlled, parallel-group study wherein, subjects will be randomised in a ratio of 1:1 to receive 2 single doses of either 4.8 milligrams GSK2798745, then 2.4 milligrams GSK2798745 12 hours later; or a dose of placebo, then another dose of placebo 12 hours later.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects between 18 and 50 years of age inclusive, at the time of signing the informed consent. * Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests (including a normal coagulation profile), ECGs, vital signs and spirometry. In the event of out-of-range results of safety tests, the tests may be repeated once within the screening window. If a retest result is again outside the reference range and considered clinically significant by the investigator and GlaxoSmithKline (GSK) medical monitor, the subject will be considered a screen failure. * Normal spirometry (FEV1 \>=80% of predicted, FEV1/FVC ratio \>=70%) at Screening and before dosing. * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 19 to 29.9 kilogram per square meter (kg/m\^2)(inclusive). * A male subject must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period. * A female is eligible to participate if she is not of childbearing potential. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Exclusion criteria
* Significant history of or current cardiovascular, respiratory (e.g., asthma, chronic obstructive pulmonary disorder (COPD), bronchiectasis, active Tuberculosis \[TB\]), hepatic, renal, gastrointestinal, endocrine, hematological, autoimmune or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data. * Subject who, in the investigator/designee's judgement, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires e.g., Type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the last 5 years. * Active ulcer disease or gastrointestinal bleeding at the time of Screening (positive FOBT at Screening). * Abnormal blood pressure as determined by the investigator. * Alanine aminotransferase (ALT) or bilirubin \>1.5 times upper limit of normal (ULN) (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * QT interval corrected for heart rate according Fridericia's formula (QTcF) \>450 milliseconds (msec). * At risk of Torsades de pointes (e.g., a personal history or a family history of sudden unexplained death, long QT, familial cardiac syndrome, or cardiomyopathy). * Chronic or acute infection within the 4 weeks before dosing, (e.g., upper and lower respiratory infection within the 4 weeks before dosing). * Major (as per investigator judgment) surgery within the last 12 weeks prior to randomisation or planned within 3 months of Screening. * Use of prescription or non-prescription drugs (except paracetamol), including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) before the first dose of study medication, unless, in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates their participation. * Where participation in the study would result in donation of blood or blood products in excess of 500 milliliters (mL) within 3 months. * The subject has participated in a clinical trial and has received an investigational product within the following time period before the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than four new chemical entities within 12 months before the first dosing day. * Presence of hepatitis B surface antigen (HBsAg) at Screening. * Positive hepatitis C antibody test result at Screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C Ribonucleic acid (RNA) test is obtained. * Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing. * A positive pre-study drug/alcohol/cotinine screen. * A positive test for immunodeficiency virus (HIV) antibody. * Regular use of known drugs of abuse. * History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. * Current smoker or a history of smoking within 6 months of screening, or a total pack year history of \>5 pack years. \[number of pack years = (number of cigarettes per day/20) x number of years smoked\].
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Adjusted Total Protein Concentration in Broncho-alveolar (BAL) Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose) | Baseline and at 26 hours post-first dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Adjusted Differential Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose) | Baseline and at 26 hours post-first dose | 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. |
| Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs | Up to Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Clinical Chemistry Parameters | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP) | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Clinical Chemistry Parameter-Total Protein | Baseline (Day -1) and at Day 2 and Day 9 | 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. |
| Change From Baseline Values for Hematology Parameters | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Hematology Parameter: Hemoglobin | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH) | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV) | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Baseline Adjusted Total Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose) | Baseline and at 26 hours post-first dose | 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. |
| Change From Baseline in Urine Potential of Hydrogen (pH) | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Change From Baseline in Urine Specific Gravity | Baseline (Day -1) and at Day 2 and Day 9 (FU/EW) | 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. |
| Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings | Up to Day 9 (FU/EW) | 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. |
| Number of Participants With Abnormal Findings During Physical Examinations | Up to Day 9 (FU/EW) | 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). |
| Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Day -1) and at 1, 6, 12, 14, 30 hours and Day 9 (FU/EW) | 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. |
| Change From Baseline in Heart Rate | Baseline (Day -1) and at 1, 6, 12, 14, 30 hours and Day 9 (FU/EW) | 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. |
| Change From Baseline in Temperature | Baseline (Day -1) and at 1, 2, 6, 8, 12, 14, 30 hours and Day 9 (FU/EW) | 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. |
| Number of Participants With Positive Fecal Occult Blood Test (FOBT) Data | At Day 9 | 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. |
| Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | 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-bronchodilator | 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. |
| Area Under the Curve During 26 Hours of GSK2798745 | 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-dose | 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). |
| Maximum Observed Plasma Concentration (Cmax) of GSK2798745 | 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-dose | Blood samples were collected at indicated time points. The 2- and 26-hour blood samples were taken immediately before BAL sampling. |
| Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count | Baseline (Day -1)and at Day 2 and Day 9 (FU/EW) | 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. |
Countries
Germany
Participant flow
Recruitment details
This was a randomized, placebo-controlled, parallel group, double-blind (sponsor-open), segmental lipopolysaccharide (LPS) challenge study of GSK2798745 in healthy participants.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 25 |
| 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. | 22 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrew consent | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | GSK2798745 | Total |
|---|---|---|---|
| Age, Continuous | 26.4 Years STANDARD_DEVIATION 5.07 | 27.1 Years STANDARD_DEVIATION 6.02 | 26.7 Years STANDARD_DEVIATION 5.48 |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 25 Participants | 22 Participants | 47 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 25 Participants | 22 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 22 |
| other Total, other adverse events | 10 / 25 | 7 / 22 |
| serious Total, serious adverse events | 0 / 25 | 0 / 22 |
Outcome results
Primary
Baseline Adjusted Total Protein Concentration in Broncho-alveolar (BAL) Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose)
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.
Time frame: Baseline and at 26 hours post-first dose
Population: Evaluable Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | 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 |
| GSK2798745 | Baseline Adjusted Total Protein Concentration in Broncho-alveolar (BAL) Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose) | 318.43 Milligrams per liter |
95% CI: [-127.07, 65.51]
95% CI: [-21.41, 31.3]
Secondary
Area Under the Curve During 26 Hours of GSK2798745
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).
Time frame: 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-dose
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve During 26 Hours of GSK2798745 | 221.27 Hour*nanograms per milliliter | Geometric Coefficient of Variation 20.8 |
Secondary
Baseline Adjusted Differential Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose)
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.
Time frame: Baseline and at 26 hours post-first dose
Population: Evaluable Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | 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 |
| GSK2798745 | Baseline Adjusted Differential Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose) | 58.54 Percentage of total cell count |
95% CI: [-6.28, 6.2]
95% CI: [-11.15, 10.16]
Secondary
Baseline Adjusted Total Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose)
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.
Time frame: Baseline and at 26 hours post-first dose
Population: Evaluable Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | 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 |
| GSK2798745 | Baseline Adjusted Total Cell Count of Neutrophils in BAL Samples at 24 Hours After Segmental LPS Challenge (26 Hours Post-first Dose) | 54.63 10^6 cells per milliliter |
95% CI: [-31.49, 22.87]
95% CI: [-48.2, 41.64]
Secondary
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
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.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 30 hours, n=25, 22 | 5.02 Millimeters of mercury | Standard Deviation 9.38 |
| GSK2798745 | 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 4.568 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 1 hour, n=25, 22 | 1.07 Millimeters of mercury | Standard Deviation 8.839 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 6 hours, n=25, 22 | 4.25 Millimeters of mercury | Standard Deviation 5.642 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 14 hours, n=24, 22 | 4.84 Millimeters of mercury | Standard Deviation 7.078 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 12 hours, n=25, 22 | -0.07 Millimeters of mercury | Standard Deviation 7.053 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 6 hours, n=25, 22 | 7.30 Millimeters of mercury | Standard Deviation 7.428 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 14 hours, n=24, 22 | 0.43 Millimeters of mercury | Standard Deviation 6.225 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, Day 9, n=25, 22 | -0.98 Millimeters of mercury | Standard Deviation 8.574 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 30 hours, n=25, 22 | 1.75 Millimeters of mercury | Standard Deviation 5.026 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 12 hours, n=25, 22 | 5.66 Millimeters of mercury | Standard Deviation 9.713 |
| GSK2798745 | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, Day 9, n=25, 22 | -0.70 Millimeters of mercury | Standard Deviation 5.719 |
Secondary
Change From Baseline in Heart Rate
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.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate | 1 hour, n=25, 22 | -3.28 Beats per minute | Standard Deviation 7.666 |
| Placebo | Change From Baseline in Heart Rate | 6 hours, n=25, 22 | 13.12 Beats per minute | Standard Deviation 8.402 |
| Placebo | Change From Baseline in Heart Rate | 12 hours, n=25, 22 | 14.56 Beats per minute | Standard Deviation 11.438 |
| Placebo | Change From Baseline in Heart Rate | 14 hours, n=24, 22 | 14.00 Beats per minute | Standard Deviation 13.808 |
| Placebo | Change From Baseline in Heart Rate | 30 hours, n=25, 22 | 14.40 Beats per minute | Standard Deviation 11.183 |
| Placebo | Change From Baseline in Heart Rate | Day 9, n=25, 22 | 1.44 Beats per minute | Standard Deviation 8.885 |
| GSK2798745 | Change From Baseline in Heart Rate | 30 hours, n=25, 22 | 17.02 Beats per minute | Standard Deviation 10.239 |
| GSK2798745 | Change From Baseline in Heart Rate | 1 hour, n=25, 22 | -3.61 Beats per minute | Standard Deviation 11.64 |
| GSK2798745 | Change From Baseline in Heart Rate | 14 hours, n=24, 22 | 11.84 Beats per minute | Standard Deviation 14.937 |
| GSK2798745 | Change From Baseline in Heart Rate | 6 hours, n=25, 22 | 11.75 Beats per minute | Standard Deviation 11.732 |
| GSK2798745 | Change From Baseline in Heart Rate | Day 9, n=25, 22 | -1.02 Beats per minute | Standard Deviation 9.749 |
| GSK2798745 | Change From Baseline in Heart Rate | 12 hours, n=25, 22 | 11.89 Beats per minute | Standard Deviation 13.917 |
Secondary
Change From Baseline in Temperature
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.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Temperature | 1 hour, n=25, 22 | -0.06 Degree celsius | Standard Deviation 0.38 |
| Placebo | Change From Baseline in Temperature | 2 hours, n=25, 22 | -0.22 Degree celsius | Standard Deviation 0.485 |
| Placebo | Change From Baseline in Temperature | 6 hours, n=25, 22 | 0.09 Degree celsius | Standard Deviation 0.411 |
| Placebo | Change From Baseline in Temperature | 8 hours, n=25, 22 | 0.12 Degree celsius | Standard Deviation 0.473 |
| Placebo | Change From Baseline in Temperature | 12 hours, n=25, 22 | 0.65 Degree celsius | Standard Deviation 0.395 |
| Placebo | Change From Baseline in Temperature | 14 hours, n=24, 22 | 0.63 Degree celsius | Standard Deviation 0.523 |
| Placebo | Change From Baseline in Temperature | 30 hours, n=25, 22 | 0.10 Degree celsius | Standard Deviation 0.434 |
| Placebo | Change From Baseline in Temperature | Day 9, n=25, 22 | -0.20 Degree celsius | Standard Deviation 0.612 |
| GSK2798745 | Change From Baseline in Temperature | Day 9, n=25, 22 | -0.11 Degree celsius | Standard Deviation 0.803 |
| GSK2798745 | Change From Baseline in Temperature | 1 hour, n=25, 22 | 0.01 Degree celsius | Standard Deviation 0.256 |
| GSK2798745 | Change From Baseline in Temperature | 12 hours, n=25, 22 | 0.74 Degree celsius | Standard Deviation 0.735 |
| GSK2798745 | Change From Baseline in Temperature | 2 hours, n=25, 22 | -0.06 Degree celsius | Standard Deviation 0.362 |
| GSK2798745 | Change From Baseline in Temperature | 30 hours, n=25, 22 | 0.26 Degree celsius | Standard Deviation 0.286 |
| GSK2798745 | Change From Baseline in Temperature | 6 hours, n=25, 22 | 0.07 Degree celsius | Standard Deviation 0.4 |
| GSK2798745 | Change From Baseline in Temperature | 14 hours, n=24, 22 | 0.84 Degree celsius | Standard Deviation 0.764 |
| GSK2798745 | Change From Baseline in Temperature | 8 hours, n=25, 22 | 0.21 Degree celsius | Standard Deviation 0.537 |
Secondary
Change From Baseline in Urine Potential of Hydrogen (pH)
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Urine Potential of Hydrogen (pH) | Day 2 | -0.3 pH | Standard Deviation 1.21 |
| Placebo | Change From Baseline in Urine Potential of Hydrogen (pH) | Day 9 | -0.4 pH | Standard Deviation 1.12 |
| GSK2798745 | Change From Baseline in Urine Potential of Hydrogen (pH) | Day 2 | 0.0 pH | Standard Deviation 1.2 |
| GSK2798745 | Change From Baseline in Urine Potential of Hydrogen (pH) | Day 9 | 0.2 pH | Standard Deviation 1.19 |
Secondary
Change From Baseline in Urine Specific Gravity
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Urine Specific Gravity | Day 2 | -0.0010 Ratio | Standard Deviation 0.00946 |
| Placebo | Change From Baseline in Urine Specific Gravity | Day 9 | -0.0004 Ratio | Standard Deviation 0.00721 |
| GSK2798745 | Change From Baseline in Urine Specific Gravity | Day 2 | 0.0016 Ratio | Standard Deviation 0.00836 |
| GSK2798745 | Change From Baseline in Urine Specific Gravity | Day 9 | -0.0041 Ratio | Standard Deviation 0.00908 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP)
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP) | Day 2 | 10.98 Milligrams per liter | Standard Deviation 7.33 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP) | Day 9 | 1.40 Milligrams per liter | Standard Deviation 2.505 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP) | Day 2 | 13.25 Milligrams per liter | Standard Deviation 9.186 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameter-C Reactive Protein (CRP) | Day 9 | 0.92 Milligrams per liter | Standard Deviation 1.825 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | ALP, Day 2 | 1.64 International units per liter | Standard Deviation 8.144 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | ALP, Day 9 | -3.20 International units per liter | Standard Deviation 7.953 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | ALT, Day 2 | 1.2 International units per liter | Standard Deviation 16.87 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | ALT, Day 9 | 4.4 International units per liter | Standard Deviation 26.94 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | AST, Day 2 | 18.4 International units per liter | Standard Deviation 109.78 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | AST, Day 9 | -0.2 International units per liter | Standard Deviation 10.79 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | CK, Day 2 | 1196.0 International units per liter | Standard Deviation 6333.76 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameters | CK, Day 9 | -239.2 International units per liter | Standard Deviation 1091.86 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | CK, Day 9 | -37.5 International units per liter | Standard Deviation 75.43 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | ALP, Day 2 | 4.00 International units per liter | Standard Deviation 7.578 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | AST, Day 2 | -2.3 International units per liter | Standard Deviation 3.97 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | ALP, Day 9 | -1.86 International units per liter | Standard Deviation 6.198 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | CK, Day 2 | -60.9 International units per liter | Standard Deviation 59.96 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | ALT, Day 2 | -3.5 International units per liter | Standard Deviation 3.08 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | AST, Day 9 | -1.7 International units per liter | Standard Deviation 3.83 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters | ALT, Day 9 | -2.6 International units per liter | Standard Deviation 5.14 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Sodium, Day 9 | -0.3 Millimoles per liter | Standard Deviation 2.1 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Calcium, Day 2 | -0.051 Millimoles per liter | Standard Deviation 0.1052 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Potassium, Day 9 | 0.085 Millimoles per liter | Standard Deviation 0.2389 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Calcium, Day 9 | 0.020 Millimoles per liter | Standard Deviation 0.0794 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Urea, Day 9 | -0.6978 Millimoles per liter | Standard Deviation 1.21927 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Glucose, Day 2 | 0.77714 Millimoles per liter | Standard Deviation 1.785548 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Sodium, Day 2 | 0.9 Millimoles per liter | Standard Deviation 2.14 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Glucose, Day 9 | 0.06813 Millimoles per liter | Standard Deviation 0.814014 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Urea, Day 2 | -0.8114 Millimoles per liter | Standard Deviation 1.10273 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) | Potassium, Day 2 | -0.445 Millimoles per liter | Standard Deviation 0.4781 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine, Day 2 | -6.4291 Micromoles per liter | Standard Deviation 8.07523 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, Day 2 | 0.8939 Micromoles per liter | Standard Deviation 0.78261 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, Day 9 | 1.1115 Micromoles per liter | Standard Deviation 6.29042 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, Day 9 | 0.3187 Micromoles per liter | Standard Deviation 1.0793 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine, Day 9 | -4.6611 Micromoles per liter | Standard Deviation 7.82718 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, Day 2 | 4.2284 Micromoles per liter | Standard Deviation 4.96144 |
Secondary
Change From Baseline Values for Clinical Chemistry Parameter-Total Protein
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Clinical Chemistry Parameter-Total Protein | Day 2 | -0.6 Grams per liter | Standard Deviation 3.5 |
| Placebo | Change From Baseline Values for Clinical Chemistry Parameter-Total Protein | Day 9 | -0.6 Grams per liter | Standard Deviation 4.2 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameter-Total Protein | Day 2 | 0.7 Grams per liter | Standard Deviation 5.35 |
| GSK2798745 | Change From Baseline Values for Clinical Chemistry Parameter-Total Protein | Day 9 | 1.0 Grams per liter | Standard Deviation 4.57 |
Secondary
Change From Baseline Values for Hematology Parameter: Hemoglobin
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Hematology Parameter: Hemoglobin | Day 2 | 0.1 Grams per liter | Standard Deviation 6.88 |
| Placebo | Change From Baseline Values for Hematology Parameter: Hemoglobin | Day 9 | -3.4 Grams per liter | Standard Deviation 6.39 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Hemoglobin | Day 2 | 1.5 Grams per liter | Standard Deviation 7.25 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Hemoglobin | Day 9 | -3.6 Grams per liter | Standard Deviation 5.7 |
Secondary
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH)
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH) | Day 2 | 0.04 Picograms | Standard Deviation 0.3 |
| Placebo | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH) | Day 9 | -0.02 Picograms | Standard Deviation 0.335 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH) | Day 2 | 0.10 Picograms | Standard Deviation 0.312 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemogloblin (MCH) | Day 9 | 0.06 Picograms | Standard Deviation 0.357 |
Secondary
Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV)
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 2 | -2.83 Femtoliters | Standard Deviation 2.755 |
| Placebo | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 9 | -2.93 Femtoliters | Standard Deviation 2.313 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 2 | -2.59 Femtoliters | Standard Deviation 1.478 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 9 | -3.15 Femtoliters | Standard Deviation 1.76 |
Secondary
Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count
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.
Time frame: Baseline (Day -1)and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count | Day 2 | -0.004 Tera cells per liter | Standard Deviation 0.2382 |
| Placebo | Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count | Day 9 | -0.118 Tera cells per liter | Standard Deviation 0.2221 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count | Day 2 | 0.038 Tera cells per liter | Standard Deviation 0.2524 |
| GSK2798745 | Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count | Day 9 | -0.128 Tera cells per liter | Standard Deviation 0.1929 |
Secondary
Change From Baseline Values for Hematology Parameters
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Values for Hematology Parameters | Basophils, Day 2 | -0.02 Giga cells per liter | Standard Deviation 0.05 |
| Placebo | Change From Baseline Values for Hematology Parameters | Basophils, Day 9 | -0.01 Giga cells per liter | Standard Deviation 0.053 |
| Placebo | Change From Baseline Values for Hematology Parameters | Eosinophils, Day 2 | -0.01 Giga cells per liter | Standard Deviation 0.067 |
| Placebo | Change From Baseline Values for Hematology Parameters | Eosinophils, Day 9 | 0.01 Giga cells per liter | Standard Deviation 0.108 |
| Placebo | Change From Baseline Values for Hematology Parameters | Lymphocytes, Day 2 | -0.67 Giga cells per liter | Standard Deviation 0.542 |
| Placebo | Change From Baseline Values for Hematology Parameters | Lymphocytes, Day 9 | -0.48 Giga cells per liter | Standard Deviation 0.471 |
| Placebo | Change From Baseline Values for Hematology Parameters | Monocytes, Day 2 | -0.04 Giga cells per liter | Standard Deviation 0.25 |
| Placebo | Change From Baseline Values for Hematology Parameters | Monocytes, Day 9 | -0.04 Giga cells per liter | Standard Deviation 0.142 |
| Placebo | Change From Baseline Values for Hematology Parameters | Neutrophils, Day 2 | 1.18 Giga cells per liter | Standard Deviation 2.346 |
| Placebo | Change From Baseline Values for Hematology Parameters | Neutrophils, Day 9 | -0.94 Giga cells per liter | Standard Deviation 1.943 |
| Placebo | Change From Baseline Values for Hematology Parameters | Platelet count, Day 2 | -16.6 Giga cells per liter | Standard Deviation 17.63 |
| Placebo | Change From Baseline Values for Hematology Parameters | Platelet count, Day 9 | 6.2 Giga cells per liter | Standard Deviation 24.19 |
| Placebo | Change From Baseline Values for Hematology Parameters | WBC count, Day 2 | 0.42 Giga cells per liter | Standard Deviation 2.323 |
| Placebo | Change From Baseline Values for Hematology Parameters | WBC count, Day 9 | -1.46 Giga cells per liter | Standard Deviation 1.999 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Platelet count, Day 2 | -15.0 Giga cells per liter | Standard Deviation 23.63 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Basophils, Day 2 | -0.01 Giga cells per liter | Standard Deviation 0.035 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Monocytes, Day 9 | -0.12 Giga cells per liter | Standard Deviation 0.123 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Basophils, Day 9 | 0.00 Giga cells per liter | Standard Deviation 0.044 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | WBC count, Day 2 | 1.50 Giga cells per liter | Standard Deviation 3.071 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Eosinophils, Day 2 | -0.05 Giga cells per liter | Standard Deviation 0.118 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Neutrophils, Day 2 | 1.89 Giga cells per liter | Standard Deviation 3.083 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Eosinophils, Day 9 | -0.05 Giga cells per liter | Standard Deviation 0.106 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Platelet count, Day 9 | 21.1 Giga cells per liter | Standard Deviation 22.29 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Lymphocytes, Day 2 | -0.40 Giga cells per liter | Standard Deviation 0.359 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Neutrophils, Day 9 | -1.14 Giga cells per liter | Standard Deviation 2.418 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Lymphocytes, Day 9 | 0.71 Giga cells per liter | Standard Deviation 4.949 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | WBC count, Day 9 | -1.65 Giga cells per liter | Standard Deviation 2.371 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters | Monocytes, Day 2 | 0.04 Giga cells per liter | Standard Deviation 0.176 |
Secondary
Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes
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.
Time frame: Baseline (Day -1) and at Day 2 and Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes | Reticulocytes, Day 9 | 0.0013 Percentage of red blood cells in blood | Standard Deviation 0.00247 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes | Hematocrit, Day 2 | -0.010 Percentage of red blood cells in blood | Standard Deviation 0.0213 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes | Reticulocytes, Day 2 | -0.0002 Percentage of red blood cells in blood | Standard Deviation 0.0015 |
| GSK2798745 | Change From Baseline Values for Hematology Parameters: Hematocrit and Reticulocytes | Hematocrit, Day 9 | -0.027 Percentage of red blood cells in blood | Standard Deviation 0.0167 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of GSK2798745
Blood samples were collected at indicated time points. The 2- and 26-hour blood samples were taken immediately before BAL sampling.
Time frame: 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-dose
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of GSK2798745 | 14.821 Nanograms per milliliter | Geometric Coefficient of Variation 17.7 |
Secondary
Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC)
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.
Time frame: 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-bronchodilator
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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FVC, Day 2, 25.5 Hours, n=23, 22 | 5.820 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FEV1, Day 1, Pre-bronchodilator, n=25, 22 | 4.744 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FVC, Day 1, Pre-bronchodilator, n=25, 22 | 5.867 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FEV1, Day 1, 6 Hours, n=25, 22 | 4.658 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FVC, Day 9, pre-bronchodilator, n=25, 22 | 5.863 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FEV1, Day 2, 25.5 Hours, n=23, 22 | 4.704 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FVC, Day 1, 6 Hours, n=25, 22 | 5.711 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FEV1, Day 2, 30 Hours, n=23, 22 | 4.617 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FVC, Day 2, 30 Hours, n=23, 22 | 5.642 Liters |
| GSK2798745 | Mean Forced Expiratory Volume in 1 Second (FEV1) and Mean Forced Vital Capacity (FVC) | FEV1, Day 9, pre-bronchodilator, n=25, 22 | 4.796 Liters |
Secondary
Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs
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.
Time frame: Up to Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs | Any SAE | 0 Participants |
| Placebo | Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs | Any non-SAE | 10 Participants |
| GSK2798745 | Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs | Any SAE | 0 Participants |
| GSK2798745 | Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs | Any non-SAE | 7 Participants |
Secondary
Number of Participants With Abnormal Findings During Physical Examinations
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).
Time frame: Up to Day 9 (FU/EW)
Population: Safety Population. This analysis was not planned and data was not collected and captured in the database.
Secondary
Number of Participants With Positive Fecal Occult Blood Test (FOBT) Data
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.
Time frame: At Day 9
Population: All Subjects Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Positive Fecal Occult Blood Test (FOBT) Data | 0 Participants |
| GSK2798745 | Number of Participants With Positive Fecal Occult Blood Test (FOBT) Data | 1 Participants |
Secondary
Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings
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.
Time frame: Up to Day 9 (FU/EW)
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal-not clinically significant | 21 Participants |
| Placebo | Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal-clinically significant | 0 Participants |
| GSK2798745 | Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal-not clinically significant | 20 Participants |
| GSK2798745 | Number of Participants With Worst Case Post Baseline Abnormal Electrocardiogram (ECG) Findings | Abnormal-clinically significant | 0 Participants |