Trial Outcomes & Findings for Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery (NCT NCT02221037)

Last Updated: 2020-10-27

Results Overview

PVPI is a derived value from extra vascular lung water (EVLW), and is considered to be less variable than extra vascular lung water Index (EVLWI). PVPI was measured via single-indicator transpulmonary thermodilution with a patent indwelling Pulse Contour Cardiac Output (PiCCO) catheter. Baseline was Day 1 (immediately prior to start of surgery). Change from Baseline value was the post-Baseline value (on completion of surgery on Day 1) minus Baseline value. Per-Protocol 1 (PP1) Population comprised of all the participants in the Safety population for whom the treatment actually received was the same one when they were randomized to (both study drug and BAL sampling location).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)

Results posted on

2020-10-27

Participant Flow

The study was conducted at 8 centers in the United Kingdom from 28-Apr-2015 to 28-Jun-2017.

A total of 54 participants (included 2 participants who were screen-failures and were re-screened) were screened, of which 21 participants (2 re-entered study) were screen-failures (SF). Reasons for SF: study procedure could not be performed (4), inclusion/exclusion criteria not met (14), study closed/terminated (1) and investigator discretion (2).

Participant milestones

Participant milestones
Measure	Placebo (BAL Collapsed Lung) Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung broncho-alveolar lavage (BAL) procedure on Day 1.	Placebo (BAL Ventilated Lung) Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 milligrams (mg) on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Overall Study STARTED	5	11	8	9
Overall Study COMPLETED	5	11	7	9
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (BAL Collapsed Lung) Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung broncho-alveolar lavage (BAL) procedure on Day 1.	Placebo (BAL Ventilated Lung) Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 milligrams (mg) on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Overall Study Physician Decision	0	0	1	0

Baseline Characteristics

Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	Total n=33 Participants Total of all reporting groups
Age, Continuous	63.0 Years STANDARD_DEVIATION 9.70 • n=5 Participants	63.5 Years STANDARD_DEVIATION 10.47 • n=7 Participants	62.0 Years STANDARD_DEVIATION 4.69 • n=5 Participants	59.3 Years STANDARD_DEVIATION 10.76 • n=4 Participants	61.9 Years STANDARD_DEVIATION 9.09 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	27 Participants n=21 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	33 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)

Population: PP1 Population.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Baseline Adjusted Change in Pulmonary Vascular Permeability Index (PVPI) on Completion of Surgery	0.00 Ratio Standard Deviation 0.367	0.11 Ratio Standard Deviation 0.664	-0.18 Ratio Standard Deviation 0.536	0.21 Ratio Standard Deviation 0.449

SECONDARY outcome

Timeframe: Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)

Population: PP1 Population.

EVLW refers to the fluid within the lung but outside the vascular compartment. It includes extravasated plasma, intracellular water, lymphatic fluid, and surfactant. EVLWI was measured by trans-pulmonary thermodilution via a PiCCO hemodynamic monitor. Baseline was Day 1 (immediately prior to start of surgery). Change from Baseline value was the post-Baseline value (on completion of surgery on Day 1) minus Baseline value. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Baseline Adjusted Change in EVLWI on Completion of Surgery	0.462 Milliliters per kilograms Standard Deviation 1.4731	-0.317 Milliliters per kilograms Standard Deviation 1.3436	0.008 Milliliters per kilograms Standard Deviation 1.2527	-0.300 Milliliters per kilograms Standard Deviation 3.8403

SECONDARY outcome

Timeframe: Up to Day 31

Population: Safety Population.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Safety Population comprised of all participants who received at least one complete dose of study treatment.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	5 Participants	10 Participants	6 Participants	9 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	3 Participants	5 Participants	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to Day 8

Population: Safety Population.

Hematology parameters included basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, neutrophil bands, platelets, red blood cell (RBC) count, segmented neutrophils and white blood cell (WBC) count. The potential clinical concern values were: hematocrit (low: \<0.3 fraction and high: \>0.54 fraction), Hemoglobin (low: \<90 gram per Liter and high: \>180 gram per Liter), lymphocytes (low: \<0.6 x 10\^9 cells/Liter and high: \>3.0 x 10\^9 cells/Liter), neutrophils: (low: \<1.5 x 10\^9 cells/Liter and high: \>20 x 10\^9 cells/Liter), platelets: (low: \<100 x 10\^9 cells/Liter and high: \>600 x 10\^9 cells/Liter) and WBC: (low: \<3 x 10\^9 cells/Liter and high: \>20 x 10\^9 cells/Liter). Only those participants for which at least one value of potential clinical concern was reported are summarized.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Hematology Abnormalities of Potential Clinical Importance	5 Participants	10 Participants	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to Day 8

Population: Safety Population.

Clinical chemistry parameters and their potential clinical concern values were: albumin (low: \<25 millimole \[mmol\]/L and high: \>60 mmol/L), calcium (low: \<1.8 mmoL/L and high: \>2.75 mmol/L), creatinine (low: \<30 mmol/L and high: \>160 mmol/L), glucose (low: \<3 mmol/L and high: \>9 mmol/L), potassium (low: \<2.5 mmol/L and high: \>5.5 mmol/L), sodium (low: \<120 mmol/L and high: \>160 mmol/L), total carbon dioxide content (low: \<16 mmol/L and high: \>35 mmol/L) and blood urea nitrogen (low: \<3 mmol/L and high: \>15 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance	4 Participants	5 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 1 (pre-dose) and Day 8

Population: Safety Population.

Urinalysis included dipstick urine test which was used to screen for glucose, ketones, occult blood and protein on Day 1 (pre-dose) and Day 8. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, ketones, occult blood and protein can be read as Trace, 1+, 2+ and 3+, indicating proportional concentrations in the urine sample.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 1 (pre-dose): 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 8: 2+	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 8: 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 1 (pre-dose): Trace	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 1 (pre-dose): 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 1 (pre-dose): 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 1 (pre-dose): Trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 1 (pre-dose): 2+	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 1 (pre-dose): 3+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 8: Trace	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine glucose: Day 8: 1+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 1 (pre-dose): 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 1 (pre-dose): 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 8: Trace	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 8: 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 8: 2+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine ketones: Day 8: 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 1 (pre-dose): Trace	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 1 (pre-dose): 1+	0 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 1 (pre-dose): 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 8: Trace	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 8: 1+	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 8: 2+	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine occult blood: Day 8: 3+	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 1 (pre-dose): Trace	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 1 (pre-dose): 1+	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 1 (pre-dose): 2+	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 1 (pre-dose): 3+	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 8: Trace	1 Participants	5 Participants	0 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 8: 1+	2 Participants	4 Participants	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 8: 2+	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters Urine protein: Day 8: 3+	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 1, 2, 4 and 8

Population: Safety Population.

Single 12-lead ECGs were obtained thereafter during the study, using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, RR and corrected QT (QTc) intervals. Number of participants with ECG values of potential clinical importance are presented.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance	5 Participants	7 Participants	4 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to Day 31

Population: Safety Population.

Vital sign measurements included systolic and diastolic blood pressure, pulse rate, temperature and respiratory rate. Vital sign measurements were measured in a semi-recumbent or supine position after 5 minutes rest. The potential clinical concern range for systolic blood pressure: \<85 and \>160 millimeters of mercury, for diastolic: \<45 and \>100 millimeters of mercury and heart rate: \<40 and \>110 beats per minute. Number of participants with vital signs of potential clinical importance are presented.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Vital Signs of Potential Clinical Importance	2 Participants	3 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)

Population: PP1 Population.

Oxygenation and function of gas exchange was assessed by the comparison of partial pressure of oxygen arterially (PaO2) divided by the fraction of oxygen that is being inspired (FiO2), sometimes referred to simply as the 'P to F ratio'. The P to F ratio was assessed at time points during the period of intubation and mechanical ventilation. An arterial blood sample was required for determination of the partial pressure of oxygen and the percentage of O2 which is being inspired was recorded at the corresponding time point. Baseline was Day 1 (immediately prior to start of surgery). Change from Baseline value was the post-Baseline value (on completion of surgery on Day 1) minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Baseline Adjusted Change in PaO2/FiO2 on Completion of Surgery	8.9 Millimiters of Mercury Standard Deviation 141.10	18.5 Millimiters of Mercury Standard Deviation 160.82	-47.5 Millimiters of Mercury Standard Deviation 252.16	11.2 Millimiters of Mercury Standard Deviation 98.12

SECONDARY outcome

Timeframe: Day 1 (on completion of surgery)

Population: PP1 Population.

Samples were collected to determine concentrations of biomarkers in BAL using an appropriately validated assay on Day 1 after completion of surgery. BAL biomarkers included soluble tumor necrosis factor receptor (STNFR) type I, free, STNFR type I, total, tumor necrosis factor alpha, interleukin 6, interleukin 8, interleukin 1 beta, monocyte chemotactic protein-1, macrophage inflammatory protein 1 alpha, macrophage inflammatory protein 1 beta, interleukin 10 and soluble receptor for advanced glycation end (sRAGE) products. Any value below limit of quantification was replaced with half the lower limit of quantification (LLQ) prior to deriving the summary measures. Mean levels of BAL biomarkers on completion of surgery are presented. Only those participants available at the specified time points were analyzed represented by n=X,X,X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Levels of BAL Biomarkers on Completion of Surgery STNFR type I, Free, n=5,9,5,8	645.5400 Picograms per milliliter Standard Deviation 398.14834	278.2529 Picograms per milliliter Standard Deviation 201.58668	106.1600 Picograms per milliliter Standard Deviation 168.39828	67.7713 Picograms per milliliter Standard Deviation 69.69634
Levels of BAL Biomarkers on Completion of Surgery Interleukin 6, n=5,9,5,8	63.580 Picograms per milliliter Standard Deviation 66.8285	138.917 Picograms per milliliter Standard Deviation 217.3948	15.844 Picograms per milliliter Standard Deviation 30.5243	43.828 Picograms per milliliter Standard Deviation 64.0092
Levels of BAL Biomarkers on Completion of Surgery STNFR I, Total, n=5,9,5,8	299.4000 Picograms per milliliter Standard Deviation 168.92556	310.8136 Picograms per milliliter Standard Deviation 307.29751	175.5660 Picograms per milliliter Standard Deviation 167.67312	183.9000 Picograms per milliliter Standard Deviation 229.72939
Levels of BAL Biomarkers on Completion of Surgery Tumor necrosis factor alpha, n=5,9,5,7	3.5110 Picograms per milliliter Standard Deviation 2.68376	24.3850 Picograms per milliliter Standard Deviation 33.67945	6.1040 Picograms per milliliter Standard Deviation 12.51974	3.7814 Picograms per milliliter Standard Deviation 5.33211
Levels of BAL Biomarkers on Completion of Surgery Interleukin 8, n=5,9,5,8	8041.600 Picograms per milliliter Standard Deviation 16369.4998	3822.170 Picograms per milliliter Standard Deviation 6270.8199	126.340 Picograms per milliliter Standard Deviation 145.1019	432.513 Picograms per milliliter Standard Deviation 731.0601
Levels of BAL Biomarkers on Completion of Surgery Interleukin 1 beta, n=5,9,5,8	70.2376 Picograms per milliliter Standard Deviation 123.55622	66.3749 Picograms per milliliter Standard Deviation 99.46797	1.1674 Picograms per milliliter Standard Deviation 0.78732	18.6054 Picograms per milliliter Standard Deviation 38.61022
Levels of BAL Biomarkers on Completion of Surgery Monocyte chemotactic protein-1, n=5,9,5,8	118.1600 Picograms per milliliter Standard Deviation 124.52553	122.2649 Picograms per milliliter Standard Deviation 170.65326	53.4260 Picograms per milliliter Standard Deviation 75.21106	51.5713 Picograms per milliliter Standard Deviation 59.72512
Levels of BAL Biomarkers on Completion of Surgery Macrophage inflammatory protein 1 alpha, n=5,9,5,8	63.348 Picograms per milliliter Standard Deviation 54.8461	165.300 Picograms per milliliter Standard Deviation 203.2446	9.140 Picograms per milliliter Standard Deviation 0.0000	23.942 Picograms per milliliter Standard Deviation 32.7837
Levels of BAL Biomarkers on Completion of Surgery Macrophage inflammatory protein 1 beta, n=5,9,5,8	142.040 Picograms per milliliter Standard Deviation 132.7086	219.891 Picograms per milliliter Standard Deviation 264.1694	28.292 Picograms per milliliter Standard Deviation 41.4424	48.413 Picograms per milliliter Standard Deviation 82.2684
Levels of BAL Biomarkers on Completion of Surgery Interleukin 10, n=5,9,5,8	1.7098 Picograms per milliliter Standard Deviation 1.93498	5.2672 Picograms per milliliter Standard Deviation 8.39023	0.5130 Picograms per milliliter Standard Deviation 0.00000	1.8123 Picograms per milliliter Standard Deviation 3.23279
Levels of BAL Biomarkers on Completion of Surgery sRAGE products, n=5,9,5,8	1440.2 Picograms per milliliter Standard Deviation 1144.89	2121.7 Picograms per milliliter Standard Deviation 2078.47	1966.0 Picograms per milliliter Standard Deviation 2734.60	1044.6 Picograms per milliliter Standard Deviation 1560.45

SECONDARY outcome

Timeframe: Day 1 (on completion of surgery)

Population: PP1 Population.

Samples were collected to determine concentrations of biomarkers in BAL using an appropriately validated assay. BAL biomarkers included C-reactive protein and total proteins. Any value below limit of quantification was replaced with half the LLQ prior to deriving the summary measures. All BAL C-reactive protein samples were below limit of quantification and all were assigned to half the LLQ prior to deriving the summary measures. Mean levels of BAL biomarkers on completion of surgery are presented. Only those participants available at the specified time points were analyzed represented by n=X,X,X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Levels of BAL Biomarkers (C-reactive Protein and Total Proteins) on Completion of Surgery C-reactive protein, n=5,9,5,8	0.04650 Milligrams per Liter Standard Deviation 0.000000	0.04650 Milligrams per Liter Standard Deviation 0.000000	0.04650 Milligrams per Liter Standard Deviation 0.000000	0.04650 Milligrams per Liter Standard Deviation 0.000000
Levels of BAL Biomarkers (C-reactive Protein and Total Proteins) on Completion of Surgery Total proteins, n=5,10,5,8	423.6 Milligrams per Liter Standard Deviation 182.80	605.1 Milligrams per Liter Standard Deviation 670.60	136.8 Milligrams per Liter Standard Deviation 108.33	303.0 Milligrams per Liter Standard Deviation 274.85

SECONDARY outcome

Timeframe: Day 1 (on completion of surgery)

Population: PP1 Population.

Samples were collected to determine concentrations of biomarkers in BAL using an appropriately validated assay. BAL biomarkers included surfactant protein D and clara cell secretory protein. Any value below limit of quantification was replaced with half the LLQ prior to deriving the summary measures. Mean levels of BAL biomarkers on completion of surgery are presented. Only those participants available at the specified time points were analyzed represented by n=X,X,X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Levels of BAL Biomarkers (Surfactant Protein and Clara Cell Secretory Protein) on Completion of Surgery Surfactant Protein D, n=5,9,5,8	411.92 Nanograms per milliliter Standard Deviation 472.487	760.04 Nanograms per milliliter Standard Deviation 898.224	872.88 Nanograms per milliliter Standard Deviation 848.358	551.31 Nanograms per milliliter Standard Deviation 943.640
Levels of BAL Biomarkers (Surfactant Protein and Clara Cell Secretory Protein) on Completion of Surgery Clara cell secretory protein, n=5,7,5,7	3635.40 Nanograms per milliliter Standard Deviation 2575.875	2131.66 Nanograms per milliliter Standard Deviation 3217.852	1000.40 Nanograms per milliliter Standard Deviation 1167.704	1409.21 Nanograms per milliliter Standard Deviation 2358.501

SECONDARY outcome

Timeframe: Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4

Population: PP1 Population.

Oxygenation and function of gas exchange was assessed by the comparison of PaO2 divided by the FiO2, sometimes referred to simply as the 'P to F ratio'. The P to F ratio was assessed at time points during the period of intubation and mechanical ventilation. An arterial blood sample was required for determination of the partial pressure of oxygen and the percentage of O2 which is being inspired was recorded at the corresponding time point. Baseline was Day 1 (immediately prior to start of surgery). Change from Baseline value was the post-Baseline value (on completion of surgery on Day 1) minus Baseline value. PP1 Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Change Over Time in PaO2/FiO2 Post-operatively on Day 2 Through to Day 4 Day 2, n=5,8,5,6	-15.1 Millimeters of Mercury Standard Deviation 171.84	-103.3 Millimeters of Mercury Standard Deviation 87.24	38.9 Millimeters of Mercury Standard Deviation 312.28	-79.3 Millimeters of Mercury Standard Deviation 199.85
Change Over Time in PaO2/FiO2 Post-operatively on Day 2 Through to Day 4 Day 3, n=5,8,5,5	-53.7 Millimeters of Mercury Standard Deviation 120.35	-43.0 Millimeters of Mercury Standard Deviation 179.64	-9.5 Millimeters of Mercury Standard Deviation 325.46	-119.0 Millimeters of Mercury Standard Deviation 148.67
Change Over Time in PaO2/FiO2 Post-operatively on Day 2 Through to Day 4 Day 4, n=5,8,5,5	-36.3 Millimeters of Mercury Standard Deviation 139.18	-123.6 Millimeters of Mercury Standard Deviation 68.14	-22.3 Millimeters of Mercury Standard Deviation 342.46	-56.5 Millimeters of Mercury Standard Deviation 123.31

SECONDARY outcome

Timeframe: Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4

Population: PP1 Population.

PVPI is a derived value from EVLW, and is considered to be less variable than EVLWI. PVPI was measured via single-indicator transpulmonary thermodilution as long as the participant remained in the ICU with a patent indwelling PiCCO catheter. Baseline was Day 1 (immediately prior to start of surgery). Change from Baseline value was the post-Baseline value minus Baseline value. PP1 Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X,X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Change Over Time in PVPI Post-operatively on Day 2 Through to Day 4 Day 2, n=5,6,3,5	-0.22 Ratio Standard Deviation 0.259	-0.27 Ratio Standard Deviation 0.427	-0.50 Ratio Standard Deviation 0.346	-0.42 Ratio Standard Deviation 0.630
Change Over Time in PVPI Post-operatively on Day 2 Through to Day 4 Day 3, n=4,6,3,5	-0.20 Ratio Standard Deviation 0.648	-0.23 Ratio Standard Deviation 0.516	-0.30 Ratio Standard Deviation 0.529	-0.32 Ratio Standard Deviation 0.756
Change Over Time in PVPI Post-operatively on Day 2 Through to Day 4 Day 4, n=3,5,2,4	-0.40 Ratio Standard Deviation 0.200	-0.24 Ratio Standard Deviation 0.666	-0.20 Ratio Standard Deviation 0.000	-0.08 Ratio Standard Deviation 0.850

SECONDARY outcome

Timeframe: Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4

Population: PP1 Population.

EVLW refers to the fluid within the lung but outside the vascular compartment. It includes extravasated plasma, intracellular water, lymphatic fluid, and surfactant. EVLWI was measured by trans-pulmonary thermodilution via a PiCCO hemodynamic monitor. Change from Baseline value was the post-Baseline value minus Baseline value. PP1 Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X,X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=10 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Change Over Time in EVLWI Post-operatively on Day 2 Through to Day 4 Day 2, n=5,6,3,5	-0.033 Millimeters per kilograms Standard Deviation 1.1203	-1.120 Millimeters per kilograms Standard Deviation 2.4825	-0.694 Millimeters per kilograms Standard Deviation 0.8710	0.604 Millimeters per kilograms Standard Deviation 1.3370
Change Over Time in EVLWI Post-operatively on Day 2 Through to Day 4 Day 3, n=4,5,3,5	0.062 Millimeters per kilograms Standard Deviation 1.2468	-0.190 Millimeters per kilograms Standard Deviation 1.4762	-0.203 Millimeters per kilograms Standard Deviation 2.3349	0.755 Millimeters per kilograms Standard Deviation 1.4801
Change Over Time in EVLWI Post-operatively on Day 2 Through to Day 4 Day 4, n=3,5,2,4	-0.621 Millimeters per kilograms Standard Deviation 0.2646	0.828 Millimeters per kilograms Standard Deviation 4.1772	0.311 Millimeters per kilograms Standard Deviation 1.9297	1.981 Millimeters per kilograms Standard Deviation 2.8449

SECONDARY outcome

Timeframe: Day 2 to Day 4

Population: PP 2 Population.

The SOFA score defines the presence and severity of dysfunction within 6 organ systems (cardiovascular, respiratory, coagulation, liver, renal, and nervous system) with a value of "0" for assigned to normal function to a maximum value of "4" for severe dysfunction in each of the organ systems. Each component of the SOFA score was added together, ranging from "0" indicating no organ dysfunction in any of the 6 organ systems, to "24" indicating maximal organ dysfunction across all 6 organ systems. Per-Protocol (PP) 2 Population comprised of all the participants in the Safety population for whom the study drug actually received was the same one they were randomized to (study drug).

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=6 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Daily Sequential Organ Failure Assessment (SOFA) Scores on Day 2 Through to Day 4 Day 3	3.4 Scores on a Scale Standard Deviation 4.72	1.5 Scores on a Scale Standard Deviation 1.80	1.8 Scores on a Scale Standard Deviation 2.86	1.6 Scores on a Scale Standard Deviation 1.43
Daily Sequential Organ Failure Assessment (SOFA) Scores on Day 2 Through to Day 4 Day 4	2.2 Scores on a Scale Standard Deviation 3.96	1.3 Scores on a Scale Standard Deviation 0.90	1.3 Scores on a Scale Standard Deviation 3.56	1.6 Scores on a Scale Standard Deviation 1.69
Daily Sequential Organ Failure Assessment (SOFA) Scores on Day 2 Through to Day 4 Day 2	1.0 Scores on a Scale Standard Deviation 2.24	1.6 Scores on a Scale Standard Deviation 1.39	1.5 Scores on a Scale Standard Deviation 2.54	2.1 Scores on a Scale Standard Deviation 1.92

SECONDARY outcome

Timeframe: Day 1 (pre-dose, 1 hour post-dose and on completion of surgery), Day 2 (24 to 26 hours post-dose) and Day 3 (46 to 50 hours post-dose)

Population: PK Population.

Blood samples for pharmacokinetic analysis of GSK2862277 were collected at the indicated time points. Pharmacokinetic (PK) Population comprised of all participants in the Safety population for whom a pharmacokinetic sample (plasma and/or BAL) was obtained and analyzed.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=3 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=6 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0 to t])	340505.15 Hours*picograms/milliliter Geometric Coefficient of Variation 45.284	290102.64 Hours*picograms/milliliter Geometric Coefficient of Variation 76.450	—	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose, 1 hour post-dose and on completion of surgery), Day 2 (24 to 26 hours post-dose) and Day 3 (46 to 50 hours post-dose)

Population: PK Population.

Blood samples for pharmacokinetic analysis of GSK2862277 were collected at the indicated time points.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=3 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=6 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Maximum Observed Concentration (Cmax)	31123.58 Picograms per milliliters Geometric Coefficient of Variation 64.452	25469.14 Picograms per milliliters Geometric Coefficient of Variation 93.307	—	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose, 1 hour post-dose and on completion of surgery), Day 2 (24 to 26 hours post-dose) and Day 3 (46 to 50 hours post-dose)

Population: PK Population.

Half-life (t1⁄2) is the time required for a quantity to reduce to half its initial value. t1/2 was not determined in all cases due to insufficient data in the terminal phase. Blood samples for pharmacokinetic analysis of GSK2862277 were collected at the indicated time points. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Derived Pharmacokinetic Parameter- Half-life (t1/2) and Time of Occurrence of Cmax (Tmax) Tmax, n=3,6	7.584 Hours Geometric Coefficient of Variation 11.4958	7.583 Hours Geometric Coefficient of Variation 11.4119	—	—

SECONDARY outcome

Timeframe: Day 1 (on completion of surgery)

Population: PP1 Population.

BAL sampling and plasma sampling was done on Day 1 (on completion of surgery). Raw summary statistics for the derived ratio were not produced. Only statistical modeling was performed that produced a posterior distribution for each treatment. Summary measure for the posterior distribution was the median. The quantity being modeled was the mean treatment effect (pooling data from BAL Collapsed and Ventilated Lungs). The standard deviation is capturing the dispersion of the estimate for the mean effect. Ratio of total protein (Ratio was derived from BAL and Plasma values) is presented.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=15 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=13 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Ratio of Total Protein Derived From BAL and Plasma Values	0.005 Ratio Standard Deviation 0.0020	0.002 Ratio Standard Deviation 0.0009	—	—

SECONDARY outcome

Timeframe: Day 8 and Day 31

Population: Safety Population.

Serum samples were obtained to determine incidence and titers of serum anti-GSK2862277 antibodies at the specified time points. The binding antibody detection assay was performed at the specified time points. Number of participants with positive immunogenicity results post-dosing is presented.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=11 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) n=8 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) n=9 Participants Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
Number of Participants With Positive Immunogenicity Results Post-dosing	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 (on completion of surgery)

Population: PK Population.

BAL samples were collected on Day 1 (on completion of surgery) and BAL concentrations of GSK2862277 and derived PK parameters were determined. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo (BAL Collapsed Lung) n=1 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	Placebo (BAL Ventilated Lung) n=5 Participants Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Collapsed Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1.	GSK2862277 26 mg (BAL Ventilated Lung) Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1.
BAL Concentrations of GSK2862277	11220.00 Nanograms per milliliter Geometric Coefficient of Variation NA Standard deviation could not calculated as a single participant was analyzed.	74155.37 Nanograms per milliliter Geometric Coefficient of Variation 377	—	—

Adverse Events

Placebo (BAL Collapsed Lung)

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo (BAL Ventilated Lung)

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

GSK2862277 26 mg (BAL Collapsed Lung)

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

GSK2862277 26 mg (BAL Ventilated Lung)

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

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