Download PDF

Clinical Trial Results:
A Placebo Controlled, Double-blind, Multi-centre, Single Dose, Parallel Group, Randomised Clinical Trial of GSK2862277 in Patients undergoing Oesophagectomy Surgery

Summary
EudraCT number	2014-000643-33
Trial protocol	GB
Global end of trial date	28 Jun 2017

Results information
Results version number	v1(current)
This version publication date	13 Jul 2018
First version publication date	13 Jul 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

116341

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Nov 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Jun 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

To evaluate whether a single nebulized dose of GSK2862277 prevents peri-operative lung injury compared to placebo, as assessed by measurement of pulmonary vascular permeability.

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Apr 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 33

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

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

Screening details

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).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo (BAL collapsed lung)

Arm description

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.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation vapour, solution

Routes of administration

Inhalation use

Dosage and administration details

It was a clear, colorless to pale yellow liquid, which was administered in volume to match active dose as solution for inhalation with duration of nebulization as approximately 3 to 5 minutes and was administered using "Pari eFlow with s30 mesh" device.

Placebo (BAL ventilated lung)

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation vapour, solution

Routes of administration

Inhalation use

Dosage and administration details

GSK2862277 26 mg (BAL collapsed lung)

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2862277

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation vapour, solution

Routes of administration

Inhalation use

Dosage and administration details

It was available as 26 mg white to off-white, uniform lyophilized cake that will be reconstituted (using reconstitution fluid formulated with polysorbate 80 in Water for Injection) to 40 mg/vial of Lyophile for reconstitution for inhalation with duration of nebulization as approximately 3 to 5 minutes and was administered using "Pari eFlow with s30 mesh" device.

GSK2862277 26 mg (BAL ventilated lung)

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2862277

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation vapour, solution

Routes of administration

Inhalation use

Dosage and administration details

Number of subjects in period 1	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Started	5	11	8	9
Completed	5	11	7	9
Not completed	0	0	1	0
Physician decision	-	-	1	-

Baseline characteristics

Top of page

Reporting group title

Placebo (BAL collapsed lung)

Reporting group description

Reporting group title

Placebo (BAL ventilated lung)

Reporting group description

Reporting group title

GSK2862277 26 mg (BAL collapsed lung)

Reporting group description

Reporting group title

GSK2862277 26 mg (BAL ventilated lung)

Reporting group description

Reporting group values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)	Total
Number of subjects	5	11	8	9
Age categorical
Units: Subjects
Age continuous
Safety Population which comprised of all participants who received at least one complete dose of study treatment.
Units: years
arithmetic mean (standard deviation)	63.0 ± 9.70	63.5 ± 10.47	62.0 ± 4.69	59.3 ± 10.76	-
Gender categorical
Safety Population which comprised of all participants who received at least one complete dose of study treatment.
Units: Subjects
Female	0	4	0	2	6
Male	5	7	8	7	27
Race/Ethnicity, Customized
Safety Population which comprised of all participants who received at least one complete dose of study treatment.
Units: Subjects
White	5	11	8	9	33

End points

Top of page

Reporting group title

Placebo (BAL collapsed lung)

Reporting group description

Reporting group title

Placebo (BAL ventilated lung)

Reporting group description

Reporting group title

GSK2862277 26 mg (BAL collapsed lung)

Reporting group description

Reporting group title

GSK2862277 26 mg (BAL ventilated lung)

Reporting group description

Subject analysis set title

Placebo (pooling BAL collapsed and ventilated lungs)

Subject analysis set type

Per protocol

Subject analysis set description

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 either collapsed lung BAL procedure or ventilated lung BAL procedure on Day 1.

Subject analysis set title

GSK2862277 26 mg (pooling BAL collapsed and ventilated lungs)

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Baseline adjusted change in Pulmonary vascular permeability index (PVPI) on completion of surgery

Top of page

End point title

Baseline adjusted change in Pulmonary vascular permeability index (PVPI) on completion of surgery ^[1]

End point description

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).

End point type

Primary

End point timeframe

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

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[2]	10 ^[3]	5 ^[4]	8 ^[5]
Units: Ratio
arithmetic mean (standard deviation)
Ratio	0.00 ± 0.367	0.11 ± 0.664	-0.18 ± 0.536	0.21 ± 0.449

Notes
[2] - PP1 Population.
[3] - PP1 Population.
[4] - PP1 Population.
[5] - PP1 Population.

No statistical analyses for this end point

Secondary: Baseline adjusted change in EVLWI on completion of surgery

Top of page

End point title

Baseline adjusted change in EVLWI on completion of surgery

End point description

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.

End point type

Secondary

End point timeframe

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

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[6]	8 ^[7]	5 ^[8]	8 ^[9]
Units: Milliliters per kilograms
arithmetic mean (standard deviation)
Milliliters per kilograms	0.462 ± 1.4731	-0.317 ± 1.3436	0.008 ± 1.2527	-0.300 ± 3.8403

Notes
[6] - PP1 Population.
[7] - PP1 Population.
[8] - PP1 Population.
[9] - PP1 Population.

No statistical analyses for this end point

Secondary: Number of participants with adverse events (AE) and serious adverse events (SAE)

Top of page

End point title

Number of participants with adverse events (AE) and serious adverse events (SAE)

End point description

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.

End point type

Secondary

End point timeframe

Up to Day 31

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[10]	11 ^[11]	8 ^[12]	9 ^[13]
Units: Participants
AE	5	10	6	9
SAE	3	5	5	4

Notes
[10] - Safety Population.
[11] - Safety Population.
[12] - Safety Population.
[13] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with hematology abnormalities of potential clinical importance

Top of page

End point title

Number of participants with hematology abnormalities of potential clinical importance

End point description

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.

End point type

Secondary

End point timeframe

Up to Day 8

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[14]	11 ^[15]	8 ^[16]	9 ^[17]
Units: Participants
Participants	5	10	5	8

Notes
[14] - Safety Population.
[15] - Safety Population.
[16] - Safety Population.
[17] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with clinical chemistry abnormalities of potential clinical importance

Top of page

End point title

Number of participants with clinical chemistry abnormalities of potential clinical importance

End point description

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.

End point type

Secondary

End point timeframe

Up to Day 8

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[18]	11 ^[19]	8 ^[20]	9 ^[21]
Units: Participants
Participants	4	5	4	4

Notes
[18] - Safety Population.
[19] - Safety Population.
[20] - Safety Population.
[21] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with abnormal urinalysis parameters

Top of page

End point title

Number of participants with abnormal urinalysis parameters

End point description

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.

End point type

Secondary

End point timeframe

Day 1 (pre-dose) and Day 8

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[22]	11 ^[23]	8 ^[24]	9 ^[25]
Units: Participants
Urine glucose: Day 1 (pre-dose): Trace	0	0	0	0
Urine glucose: Day 1 (pre-dose): 1+	0	0	0	0
Urine glucose: Day 1 (pre-dose): 2+	1	0	0	0
Urine glucose: Day 1 (pre-dose): 3+	0	0	1	0
Urine glucose: Day 8: Trace	0	1	0	2
Urine glucose: Day 8: 1+	0	0	0	0
Urine glucose: Day 8: 2+	1	0	0	0
Urine glucose: Day 8: 3+	0	0	0	0
Urine ketones: Day 1 (pre-dose): Trace	1	0	1	0
Urine ketones: Day 1 (pre-dose): 1+	0	0	0	0
Urine ketones: Day 1 (pre-dose): 2+	0	0	0	0
Urine ketones: Day 1 (pre-dose): 3+	0	0	0	0
Urine ketones: Day 8: Trace	0	0	0	2
Urine ketones: Day 8: 1+	0	0	1	0
Urine ketones: Day 8: 2+	0	0	0	0
Urine ketones: Day 8: 3+	0	0	0	0
Urine occult blood: Day 1 (pre-dose): Trace	0	0	1	0
Urine occult blood: Day 1 (pre-dose): 1+	0	2	1	0
Urine occult blood: Day 1 (pre-dose): 2+	0	0	0	0
Urine occult blood: Day 1 (pre-dose): 3+	0	0	0	0
Urine occult blood: Day 8: Trace	0	0	0	0
Urine occult blood: Day 8: 1+	1	1	0	0
Urine occult blood: Day 8: 2+	0	0	0	2
Urine occult blood: Day 8: 3+	0	1	0	0
Urine protein: Day 1 (pre-dose): Trace	0	0	0	2
Urine protein: Day 1 (pre-dose): 1+	1	0	1	0
Urine protein: Day 1 (pre-dose): 2+	0	1	0	1
Urine protein: Day 1 (pre-dose): 3+	0	0	0	0
Urine protein: Day 8: Trace	1	5	0	3
Urine protein: Day 8: 1+	2	4	2	2
Urine protein: Day 8: 2+	0	0	1	2
Urine protein: Day 8: 3+	0	0	0	0

Notes
[22] - Safety Population.
[23] - Safety Population.
[24] - Safety Population.
[25] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with electrocardiogram (ECG) values of potential clinical importance

Top of page

End point title

Number of participants with electrocardiogram (ECG) values of potential clinical importance

End point description

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.

End point type

Secondary

End point timeframe

Days 1, 2, 4 and 8

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[26]	11 ^[27]	8 ^[28]	9 ^[29]
Units: Participants
Participants	5	7	4	8

Notes
[26] - Safety Population.
[27] - Safety Population.
[28] - Safety Population.
[29] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with vital signs of potential clinical importance

Top of page

End point title

Number of participants with vital signs of potential clinical importance

End point description

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.

End point type

Secondary

End point timeframe

Up to Day 31

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[30]	11 ^[31]	8 ^[32]	9 ^[33]
Units: Participants
Participants	2	3	3	3

Notes
[30] - Safety Population.
[31] - Safety Population.
[32] - Safety Population.
[33] - Safety Population.

No statistical analyses for this end point

Secondary: Baseline adjusted change in PaO2/FiO2 on completion of surgery

Top of page

End point title

Baseline adjusted change in PaO2/FiO2 on completion of surgery

End point description

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.

End point type

Secondary

End point timeframe

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

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[34]	10 ^[35]	5 ^[36]	8 ^[37]
Units: Millimiters of Mercury
arithmetic mean (standard deviation)
Millimiters of Mercury	8.9 ± 141.10	18.5 ± 160.82	-47.5 ± 252.16	11.2 ± 98.12

Notes
[34] - PP1 Population.
[35] - PP1 Population.
[36] - PP1 Population.
[37] - PP1 Population.

No statistical analyses for this end point

Secondary: Levels of BAL biomarkers on completion of surgery

Top of page

End point title

Levels of BAL biomarkers on completion of surgery

End point description

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.

End point type

Secondary

End point timeframe

Day 1 (on completion of surgery)

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[38]	10 ^[39]	5 ^[40]	8 ^[41]
Units: Picograms per milliliter
arithmetic mean (standard deviation)
STNFR type I, Free, n=5,9,5,8	645.5400 ± 398.14834	278.2529 ± 201.58668	106.1600 ± 168.39828	67.7713 ± 69.69634
STNFR I, Total, n=5,9,5,8	299.4000 ± 168.92556	310.8136 ± 307.29751	175.5660 ± 167.67312	183.9000 ± 229.72939
Tumor necrosis factor alpha, n=5,9,5,7	3.5110 ± 2.68376	24.3850 ± 33.67945	6.1040 ± 12.51974	3.7814 ± 5.33211
Interleukin 6, n=5,9,5,8	63.580 ± 66.8285	138.917 ± 217.3948	15.844 ± 30.5243	43.828 ± 64.0092
Interleukin 8, n=5,9,5,8	8041.600 ± 16369.4998	3822.170 ± 6270.8199	126.340 ± 145.1019	432.513 ± 731.0601
Interleukin 1 beta, n=5,9,5,8	70.2376 ± 123.55622	66.3749 ± 99.46797	1.1674 ± 0.78732	18.6054 ± 38.61022
Monocyte chemotactic protein-1, n=5,9,5,8	118.1600 ± 124.52553	122.2649 ± 170.65326	53.4260 ± 75.21106	51.5713 ± 59.72512
Macrophage inflammatory protein 1 alpha, n=5,9,5,8	63.348 ± 54.8461	165.300 ± 203.2446	9.140 ± 0.0000	23.942 ± 32.7837
Macrophage inflammatory protein 1 beta, n=5,9,5,8	142.040 ± 132.7086	219.891 ± 264.1694	28.292 ± 41.4424	48.413 ± 82.2684
Interleukin 10, n=5,9,5,8	1.7098 ± 1.93498	5.2672 ± 8.39023	0.5130 ± 0.00000	1.8123 ± 3.23279
sRAGE products, n=5,9,5,8	1440.2 ± 1144.89	2121.7 ± 2078.47	1966.0 ± 2734.60	1044.6 ± 1560.45

Notes
[38] - PP1 Population.
[39] - PP1 Population.
[40] - PP1 Population.
[41] - PP1 Population.

No statistical analyses for this end point

Secondary: Levels of BAL biomarkers (C-reactive protein and total proteins) on completion of surgery

Top of page

End point title

Levels of BAL biomarkers (C-reactive protein and total proteins) on completion of surgery

End point description

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.

End point type

Secondary

End point timeframe

Day 1 (on completion of surgery)

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[42]	10 ^[43]	5 ^[44]	8 ^[45]
Units: Milligrams per Liters
arithmetic mean (standard deviation)
C-reactive protein, n=5,9,5,8	0.04650 ± 0.000000	0.04650 ± 0.000000	0.04650 ± 0.000000	0.04650 ± 0.000000
Total proteins, n=5,10,5,8	423.6 ± 182.80	605.1 ± 670.60	136.8 ± 108.33	303.0 ± 274.85

Notes
[42] - PP1 Population.
[43] - PP1 Population.
[44] - PP1 Population.
[45] - PP1 Population.

No statistical analyses for this end point

Secondary: Levels of BAL biomarkers (surfactant protein and clara cell secretory protein) on completion of surgery

Top of page

End point title

Levels of BAL biomarkers (surfactant protein and clara cell secretory protein) on completion of surgery

End point description

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.

End point type

Secondary

End point timeframe

Day 1 (on completion of surgery)

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[46]	10 ^[47]	5 ^[48]	8 ^[49]
Units: Nanograms per milliliter
arithmetic mean (standard deviation)
Surfactant Protein D, n=5,9,5,8	411.92 ± 472.487	760.04 ± 898.224	872.88 ± 848.358	551.31 ± 943.640
Clara cell secretory protein, n=5,7,5,7	3635.40 ± 2575.875	2131.66 ± 3217.852	1000.40 ± 1167.704	1409.21 ± 2358.501

Notes
[46] - PP1 Population.
[47] - PP1 Population.
[48] - PP1 Population.
[49] - PP1 Population.

No statistical analyses for this end point

Secondary: Change over time in PaO2/FiO2 post-operatively on Day 2 through to Day 4

Top of page

End point title

Change over time in PaO2/FiO2 post-operatively on Day 2 through to Day 4

End point description

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.

End point type

Secondary

End point timeframe

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

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[50]	10 ^[51]	5 ^[52]	8 ^[53]
Units: Millimeters of Mercury
arithmetic mean (standard deviation)
Day 2, n=5,8,5,6	-15.1 ± 171.84	-103.3 ± 87.24	38.9 ± 312.28	-79.3 ± 199.85
Day 3, n=5,8,5,5	-53.7 ± 120.35	-43.0 ± 179.64	-9.5 ± 325.46	-119.0 ± 148.67
Day 4, n=5,8,5,5	-36.3 ± 139.18	-123.6 ± 68.14	-22.3 ± 342.46	-56.5 ± 123.31

Notes
[50] - PP1 Population.
[51] - PP1 Population.
[52] - PP1 Population.
[53] - PP1 Population.

No statistical analyses for this end point

Secondary: Change over time in PVPI post-operatively on Day 2 through to Day 4

Top of page

End point title

Change over time in PVPI post-operatively on Day 2 through to Day 4

End point description

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.

End point type

Secondary

End point timeframe

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

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[54]	10 ^[55]	5 ^[56]	8 ^[57]
Units: Ratio
arithmetic mean (standard deviation)
Day 2, n=5,6,3,5	-0.22 ± 0.259	-0.27 ± 0.427	-0.50 ± 0.346	-0.42 ± 0.630
Day 3, n=4,6,3,5	-0.20 ± 0.648	-0.23 ± 0.516	-0.30 ± 0.529	-0.32 ± 0.756
Day 4, n=3,5,2,4	-0.40 ± 0.200	-0.24 ± 0.666	-0.20 ± 0.000	-0.08 ± 0.850

Notes
[54] - PP1 Population.
[55] - PP1 Population.
[56] - PP1 Population.
[57] - PP1 Population.

No statistical analyses for this end point

Secondary: Change over time in EVLWI post-operatively on Day 2 through to Day 4

Top of page

End point title

Change over time in EVLWI post-operatively on Day 2 through to Day 4

End point description

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.

End point type

Secondary

End point timeframe

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

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[58]	10 ^[59]	5 ^[60]	8 ^[61]
Units: Millimeters per kilogram
arithmetic mean (standard deviation)
Day 2, n=5,6,3,5	-0.033 ± 1.1203	-1.120 ± 2.4825	-0.694 ± 0.8710	0.604 ± 1.3370
Day 3, n=4,5,3,5	0.062 ± 1.2468	-0.190 ± 1.4762	-0.203 ± 2.3349	0.755 ± 1.4801
Day 4, n=3,5,2,4	-0.621 ± 0.2646	0.828 ± 4.1772	0.311 ± 1.9297	1.981 ± 2.8449

Notes
[58] - PP1 Population.
[59] - PP1 Population.
[60] - PP1 Population.
[61] - PP1 Population.

No statistical analyses for this end point

Secondary: Daily Sequential Organ Failure Assessment (SOFA) scores on Day 2 through to Day 4

Top of page

End point title

Daily Sequential Organ Failure Assessment (SOFA) scores on Day 2 through to Day 4

End point description

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).

End point type

Secondary

End point timeframe

Day 2 to Day 4

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[62]	11 ^[63]	6 ^[64]	8 ^[65]
Units: Scores on a Scale
arithmetic mean (standard deviation)
Day 2	1.0 ± 2.24	1.6 ± 1.39	1.5 ± 2.54	2.1 ± 1.92
Day 3	3.4 ± 4.72	1.5 ± 1.80	1.8 ± 2.86	1.6 ± 1.43
Day 4	2.2 ± 3.96	1.3 ± 0.90	1.3 ± 3.56	1.6 ± 1.69

Notes
[62] - PP 2 Population.
[63] - PP 2 Population.
[64] - PP 2 Population.
[65] - PP 2 Population.

No statistical analyses for this end point

Secondary: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0 to t])

Top of page

End point title

Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0 to t]) ^[66]

End point description

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. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point 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)

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	3 ^[67]	6 ^[68]
Units: Hours*picograms/milliliter
geometric mean (geometric coefficient of variation)
Hours*picograms/milliliter	340505.15 ± 45.284	290102.64 ± 76.450

Notes
[67] - PK Population.
[68] - PK Population.

No statistical analyses for this end point

Secondary: Maximum observed concentration (Cmax)

Top of page

End point title

Maximum observed concentration (Cmax) ^[69]

End point description

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.

End point type

Secondary

End point 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)

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	3 ^[70]	6 ^[71]
Units: Picograms per milliliter
geometric mean (geometric coefficient of variation)
Picograms per milliliters	31123.58 ± 64.452	25469.14 ± 93.307

Notes
[70] - PK Population.
[71] - PK Population.

No statistical analyses for this end point

Secondary: Derived pharmacokinetic parameter- Half-life (t1/2) and time of occurrence of Cmax (Tmax)

Top of page

End point title

Derived pharmacokinetic parameter- Half-life (t1/2) and time of occurrence of Cmax (Tmax) ^[72]

End point description

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.

End point type

Secondary

End point 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)

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	8 ^[73]	9 ^[74]
Units: Hours
geometric mean (geometric coefficient of variation)
t1/2, n=0,0	99999 ± 99999	99999 ± 99999
Tmax, n=3,6	7.584 ± 11.4958	7.583 ± 11.4119

Notes
[73] - PK Population.
[74] - PK Population.

No statistical analyses for this end point

Secondary: Ratio of total protein derived from BAL and plasma values

Top of page

End point title

Ratio of total protein derived from BAL and plasma values

End point description

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.

End point type

Secondary

End point timeframe

Day 1 (on completion of surgery)

End point values	Placebo (pooling BAL collapsed and ventilated lungs)	GSK2862277 26 mg (pooling BAL collapsed and ventilated lungs)
Number of subjects analysed	15 ^[75]	13 ^[76]
Units: Ratio
median (standard deviation)
Ratio	0.005 ± 0.0020	0.002 ± 0.0009

Notes
[75] - PP1 Population.
[76] - PP1 Population.

No statistical analyses for this end point

Secondary: Number of participants with positive immunogenicity results post-dosing

Top of page

End point title

Number of participants with positive immunogenicity results post-dosing

End point description

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.

End point type

Secondary

End point timeframe

Day 8 and Day 31

End point values	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	5 ^[77]	11 ^[78]	8 ^[79]	9 ^[80]
Units: Participants
Participants	0	0	0	0

Notes
[77] - Safety Population.
[78] - Safety Population.
[79] - Safety Population.
[80] - Safety Population.

No statistical analyses for this end point

Secondary: BAL concentrations of GSK2862277

Top of page

End point title

BAL concentrations of GSK2862277 ^[81]

End point description

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. 99999 indicates that standard deviation could not be calculated because a single participant was analyzed.

End point type

Secondary

End point timeframe

Day 1 (on completion of surgery)

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.

End point values	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Number of subjects analysed	1 ^[82]	5 ^[83]
Units: Nanograms per milliliter
geometric mean (geometric coefficient of variation)
Nanograms per milliliter	11220.00 ± 99999	74155.37 ± 377

Notes
[82] - PK Population.
[83] - PK Population.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Serious adverse events and non-serious adverse events were collected from start of the study medication (Day 1) to Follow-up (Day 31)

Adverse event reporting additional description

Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one complete dose of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Placebo (BAL collapsed lung)

Reporting group description

Reporting group title

Placebo (BAL ventilated lung)

Reporting group description

Reporting group title

GSK2862277 26 mg (BAL collapsed lung)

Reporting group description

Reporting group title

GSK2862277 26 mg (BAL ventilated lung)

Reporting group description

Serious adverse events	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 5 (60.00%)	5 / 11 (45.45%)	5 / 8 (62.50%)	4 / 9 (44.44%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Failure to anastomose
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anastomotic leak
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	2 / 9 (22.22%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Iatrogenic injury
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pneumothorax
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Femoral artery embolism
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Splenic infarction
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Complication associated with device
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diaphragmatic hernia
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal ischaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Aspiration
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	2 / 5 (40.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chylothorax
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diaphragmatic rupture
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Delirium
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Empyema
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 5 (0.00%)	2 / 11 (18.18%)	2 / 8 (25.00%)	1 / 9 (11.11%)
occurrences causally related to treatment / all	0 / 0	0 / 2	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo (BAL collapsed lung)	Placebo (BAL ventilated lung)	GSK2862277 26 mg (BAL collapsed lung)	GSK2862277 26 mg (BAL ventilated lung)
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 5 (100.00%)	10 / 11 (90.91%)	5 / 8 (62.50%)	8 / 9 (88.89%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lymph nodes
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	1	1	1	0
Hypotension
subjects affected / exposed	2 / 5 (40.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	2	0	1	1
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)
occurrences all number	0	0	0	2
Fatigue
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Hypothermia
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Pyrexia
subjects affected / exposed	1 / 5 (20.00%)	3 / 11 (27.27%)	2 / 8 (25.00%)	1 / 9 (11.11%)
occurrences all number	1	3	3	1
Catheter site haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Catheter site pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Catheter site haematoma
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Catheter site discharge
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Complication associated with device
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Atelectasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Cough
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	2 / 9 (22.22%)
occurrences all number	1	1	0	3
Hypoxia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Lung consolidation
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Pleural effusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	2 / 8 (25.00%)	0 / 9 (0.00%)
occurrences all number	0	0	2	0
Pleuritic pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Pneumothorax
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Respiratory failure
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Respiratory tract irritation
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)
occurrences all number	0	0	0	2
Tachypnoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Throat irritation
subjects affected / exposed	1 / 5 (20.00%)	3 / 11 (27.27%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	4	0	0
Wheezing
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Oropharyngeal discomfort
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	0	0	1	1
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Confusional state
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	1	1	0
Delirium
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	1	0	1	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 5 (40.00%)	2 / 11 (18.18%)	2 / 8 (25.00%)	2 / 9 (22.22%)
occurrences all number	2	2	2	2
Blood albumin decreased
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	1	1	0
Blood calcium decreased
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Blood creatinine increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Blood lactic acid increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Blood sodium decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Blood urea increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
C-reactive protein increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	0	0	1	1
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 5 (0.00%)	3 / 11 (27.27%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	3	0	0
Glomerular filtration rate decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Haematocrit decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Haemoglobin decreased
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	1	0	0	1
Lymphocyte count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	2	0
Monocyte count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Neutrophil count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	2	0
Oxygen saturation decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	0	0	2	1
Platelet count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
PO2 decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Red blood cell count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Reticulocyte count increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
White blood cell count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
White blood cell count increased
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	0	1	1	1
Blood phosphorus decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	3 / 9 (33.33%)
occurrences all number	0	0	0	3
Platelet count increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	2 / 8 (25.00%)	0 / 9 (0.00%)
occurrences all number	0	0	2	0
Nasogastric output high
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Fungal test positive
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 5 (0.00%)	4 / 11 (36.36%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	4	1	0
Urine output decreased
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Electrocardiogram change
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Staphylococcus test positive
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	1	0	1
Streptococcus test positive
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Escherichia test positive
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Klebsiella test positive
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	2	0	0	0
Nuclear magnetic resonance imaging spinal abnormal
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Injury, poisoning and procedural complications
Anaemia postoperative
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Postoperative hernia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Postoperative thoracic procedure complication
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Procedural complication
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Procedural hypotension
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	1	0	1	0
Endotracheal intubation complication
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Procedural pain
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	1	1	1	0
Unintentional medical device removal
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	2 / 5 (40.00%)	2 / 11 (18.18%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	2	2	1	2
Atrial flutter
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Bradycardia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Tachycardia
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	2 / 8 (25.00%)	0 / 9 (0.00%)
occurrences all number	0	1	2	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	1	0	0	1
Dizziness postural
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)
occurrences all number	0	0	0	2
Hypoaesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Presyncope
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 5 (20.00%)	3 / 11 (27.27%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	3	0	0
Anaemia folate deficiency
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Diabetic retinopathy
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Diplopia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Visual acuity reduced
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	2 / 5 (40.00%)	0 / 11 (0.00%)	2 / 8 (25.00%)	1 / 9 (11.11%)
occurrences all number	2	0	2	1
Diarrhoea
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	1	0	1
Dry mouth
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Haematochezia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Impaired gastric emptying
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Nausea
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	2 / 8 (25.00%)	1 / 9 (11.11%)
occurrences all number	1	1	2	1
Vomiting
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	0	0	2	1
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Pollakiuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Urinary retention
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Urine odour abnormal
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Acute kidney injury
subjects affected / exposed	0 / 5 (0.00%)	2 / 11 (18.18%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	2	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Joint swelling
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal pain
subjects affected / exposed	2 / 5 (40.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	2 / 9 (22.22%)
occurrences all number	2	0	1	2
Joint range of motion decreased
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Injection site abscess
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Lower respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	3 / 8 (37.50%)	1 / 9 (11.11%)
occurrences all number	0	0	3	1
Oral candidiasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Pneumonia
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	1	0	0
Pneumonia klebsiella
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Postoperative wound infection
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	0	0	0
Febrile infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Enterobacter sepsis
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Staphylococcal infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Wound infection staphylococcal
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	1	1	0	0
Klebsiella infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Device related infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Infectious pleural effusion
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Stoma site cellulitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	0	0	0	1
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	1	1	0
Hypoalbuminaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Hypocalcaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Hypoglycaemia
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 9 (0.00%)
occurrences all number	0	1	0	0
Hypokalaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	2 / 8 (25.00%)	1 / 9 (11.11%)
occurrences all number	0	0	2	1
Hypomagnesaemia
subjects affected / exposed	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	1 / 9 (11.11%)
occurrences all number	0	1	1	1
Hypophosphataemia
subjects affected / exposed	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 9 (11.11%)
occurrences all number	1	1	0	1
Hypoproteinaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Magnesium deficiency
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0
Mineral deficiency
subjects affected / exposed	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)
occurrences all number	0	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

02 Jun 2014

The amendment was made to correct an error in the study title and to revise the limits on exclusion criteria for alcohol consumption.

23 Jul 2014

The amendment was made to reduce the upper threshold for Aspartate aminotransferase (AST) & Alanine aminotransferase (ALT) liver enzyme values for inclusion in the study, as per instruction from the United Kingdom (UK) competent authority (Medicines and Healthcare Regulatory Authority [MHRA]). A change to the corrected QT (QTc) inclusion criteria was also made to correct an error not previously identified.

16 Nov 2014

The amendment was made to account for the possibility of inoperable cases during the initial stages of oesophagectomy surgery, where participants would have to be withdrawn; additional time window for dosing; amending randomization window to up to 72 hours prior to day of surgery. Blood sample aliquots for a translational sub-study clarified, materials and methods of dose preparation added as an appendix. Additional minor/typographical updates and typographical changes have also been made.

16 Feb 2015

The amendment was made to remove the mandatory 1 hour post-dose electrocardiogram (ECG) due to concerns over logistics prior to surgery (on the condition that alternative cardiac monitoring is in place). Also, a 24 hour window has been added for the pre-dose assessments and a typographical error in exclusion criteria number 6 has been amended. A pharmacokinetic (PK) sample has also been included if a liver event occurs as this had been omitted in error. The opportunity has also been taken to make some other minor amendments.

23 Aug 2016

The amendment was made to detail the inclusion of an external expert to the safety review team. The opportunity has also been taken to make some other minor amendments.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
17 Dec 2015	Placebo/diluent to match inhaled GSK2862277 (placebo) on stability test delivered an out of specification (OOS) result for the Visual Inspection Test requiring a recall and temporary halt.	18 Jan 2016

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Placebo Controlled, Double-blind, Multi-centre, Single Dose, Parallel Group, Randomised Clinical Trial of GSK2862277 in Patients undergoing Oesophagectomy Surgery

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Baseline adjusted change in Pulmonary vascular permeability index (PVPI) on completion of surgery

Primary: Baseline adjusted change in Pulmonary vascular permeability index (PVPI) on completion of surgery

Secondary: Baseline adjusted change in EVLWI on completion of surgery

Secondary: Baseline adjusted change in EVLWI on completion of surgery

Secondary: Number of participants with adverse events (AE) and serious adverse events (SAE)

Secondary: Number of participants with adverse events (AE) and serious adverse events (SAE)

Secondary: Number of participants with hematology abnormalities of potential clinical importance

Secondary: Number of participants with hematology abnormalities of potential clinical importance

Secondary: Number of participants with clinical chemistry abnormalities of potential clinical importance

Secondary: Number of participants with clinical chemistry abnormalities of potential clinical importance

Secondary: Number of participants with abnormal urinalysis parameters

Secondary: Number of participants with abnormal urinalysis parameters

Secondary: Number of participants with electrocardiogram (ECG) values of potential clinical importance

Secondary: Number of participants with electrocardiogram (ECG) values of potential clinical importance

Secondary: Number of participants with vital signs of potential clinical importance

Secondary: Number of participants with vital signs of potential clinical importance

Secondary: Baseline adjusted change in PaO2/FiO2 on completion of surgery

Secondary: Baseline adjusted change in PaO2/FiO2 on completion of surgery

Secondary: Levels of BAL biomarkers on completion of surgery

Secondary: Levels of BAL biomarkers on completion of surgery

Secondary: Levels of BAL biomarkers (C-reactive protein and total proteins) on completion of surgery

Secondary: Levels of BAL biomarkers (C-reactive protein and total proteins) on completion of surgery

Secondary: Levels of BAL biomarkers (surfactant protein and clara cell secretory protein) on completion of surgery

Secondary: Levels of BAL biomarkers (surfactant protein and clara cell secretory protein) on completion of surgery

Secondary: Change over time in PaO2/FiO2 post-operatively on Day 2 through to Day 4

Secondary: Change over time in PaO2/FiO2 post-operatively on Day 2 through to Day 4

Secondary: Change over time in PVPI post-operatively on Day 2 through to Day 4

Secondary: Change over time in PVPI post-operatively on Day 2 through to Day 4

Secondary: Change over time in EVLWI post-operatively on Day 2 through to Day 4

Secondary: Change over time in EVLWI post-operatively on Day 2 through to Day 4

Secondary: Daily Sequential Organ Failure Assessment (SOFA) scores on Day 2 through to Day 4

Secondary: Daily Sequential Organ Failure Assessment (SOFA) scores on Day 2 through to Day 4

Secondary: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0 to t])

Secondary: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0 to t])

Secondary: Maximum observed concentration (Cmax)

Secondary: Maximum observed concentration (Cmax)

Secondary: Derived pharmacokinetic parameter- Half-life (t1/2) and time of occurrence of Cmax (Tmax)

Secondary: Derived pharmacokinetic parameter- Half-life (t1/2) and time of occurrence of Cmax (Tmax)

Secondary: Ratio of total protein derived from BAL and plasma values

Secondary: Ratio of total protein derived from BAL and plasma values

Secondary: Number of participants with positive immunogenicity results post-dosing

Secondary: Number of participants with positive immunogenicity results post-dosing

Secondary: BAL concentrations of GSK2862277

Secondary: BAL concentrations of GSK2862277

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Placebo Controlled, Double-blind, Multi-centre, Single Dose, Parallel Group, Randomised Clinical Trial of GSK2862277 in Patients undergoing Oesophagectomy Surgery