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Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02221037
Recruitment Status : Terminated (The study was terminated on the basis that protocol defined stopping criteria had been met.)
First Posted : August 20, 2014
Results First Posted : January 11, 2019
Last Update Posted : October 27, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Lung Injury, Acute and Respiratory Distress Syndrome, Adult
Interventions Drug: GSK2862277
Drug: Placebo
Enrollment 35
Recruitment Details The study was conducted at 8 centers in the United Kingdom from 28-Apr-2015 to 28-Jun-2017.
Pre-assignment 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).
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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. 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. 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. 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.
Period Title: Overall Study
Started 5 11 8 9
Completed 5 11 7 9
Not Completed 0 0 1 0
Reason Not Completed
Physician Decision             0             0             1             0
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung) Total
Hide Arm/Group 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 BAL procedure on Day 1. 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 5 11 8 9 33
Hide Baseline Analysis Population Description
Safety Population which comprised of all participants who received at least one complete dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 11 participants 8 participants 9 participants 33 participants
63.0  (9.70) 63.5  (10.47) 62.0  (4.69) 59.3  (10.76) 61.9  (9.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 11 participants 8 participants 9 participants 33 participants
Female
0
   0.0%
4
  36.4%
0
   0.0%
2
  22.2%
6
  18.2%
Male
5
 100.0%
7
  63.6%
8
 100.0%
7
  77.8%
27
  81.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 5 participants 11 participants 8 participants 9 participants 33 participants
5
 100.0%
11
 100.0%
8
 100.0%
9
 100.0%
33
 100.0%
1.Primary Outcome
Title Baseline Adjusted Change in Pulmonary Vascular Permeability Index (PVPI) on Completion of Surgery
Hide 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).
Time Frame Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Ratio
0.00  (0.367) 0.11  (0.664) -0.18  (0.536) 0.21  (0.449)
2.Secondary Outcome
Title Baseline Adjusted Change in EVLWI on Completion of Surgery
Hide 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.
Time Frame Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 8 5 8
Mean (Standard Deviation)
Unit of Measure: Milliliters per kilograms
0.462  (1.4731) -0.317  (1.3436) 0.008  (1.2527) -0.300  (3.8403)
3.Secondary Outcome
Title Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide 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.
Time Frame Up to Day 31
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: Participants
AE 5 10 6 9
SAE 3 5 5 4
4.Secondary Outcome
Title Number of Participants With Hematology Abnormalities of Potential Clinical Importance
Hide 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.
Time Frame Up to Day 8
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: Participants
5 10 5 8
5.Secondary Outcome
Title Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
Hide 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.
Time Frame Up to Day 8
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: Participants
4 5 4 4
6.Secondary Outcome
Title Number of Participants With Abnormal Urinalysis Parameters
Hide 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.
Time Frame Day 1 (pre-dose) and Day 8
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: 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
7.Secondary Outcome
Title Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance
Hide 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.
Time Frame Days 1, 2, 4 and 8
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: Participants
5 7 4 8
8.Secondary Outcome
Title Number of Participants With Vital Signs of Potential Clinical Importance
Hide 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.
Time Frame Up to Day 31
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: Participants
2 3 3 3
9.Secondary Outcome
Title Baseline Adjusted Change in PaO2/FiO2 on Completion of Surgery
Hide 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.
Time Frame Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Millimiters of Mercury
8.9  (141.10) 18.5  (160.82) -47.5  (252.16) 11.2  (98.12)
10.Secondary Outcome
Title Levels of BAL Biomarkers on Completion of Surgery
Hide 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.
Time Frame Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Picograms per milliliter
STNFR type I, Free, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
645.5400  (398.14834) 278.2529  (201.58668) 106.1600  (168.39828) 67.7713  (69.69634)
STNFR I, Total, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
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 Number Analyzed 5 participants 9 participants 5 participants 7 participants
3.5110  (2.68376) 24.3850  (33.67945) 6.1040  (12.51974) 3.7814  (5.33211)
Interleukin 6, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
63.580  (66.8285) 138.917  (217.3948) 15.844  (30.5243) 43.828  (64.0092)
Interleukin 8, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
8041.600  (16369.4998) 3822.170  (6270.8199) 126.340  (145.1019) 432.513  (731.0601)
Interleukin 1 beta, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
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 Number Analyzed 5 participants 9 participants 5 participants 8 participants
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 Number Analyzed 5 participants 9 participants 5 participants 8 participants
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 Number Analyzed 5 participants 9 participants 5 participants 8 participants
142.040  (132.7086) 219.891  (264.1694) 28.292  (41.4424) 48.413  (82.2684)
Interleukin 10, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
1.7098  (1.93498) 5.2672  (8.39023) 0.5130  (0.00000) 1.8123  (3.23279)
sRAGE products, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
1440.2  (1144.89) 2121.7  (2078.47) 1966.0  (2734.60) 1044.6  (1560.45)
11.Secondary Outcome
Title Levels of BAL Biomarkers (C-reactive Protein and Total Proteins) on Completion of Surgery
Hide 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.
Time Frame Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Milligrams per Liter
C-reactive protein, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
0.04650  (0.000000) 0.04650  (0.000000) 0.04650  (0.000000) 0.04650  (0.000000)
Total proteins, n=5,10,5,8 Number Analyzed 5 participants 10 participants 5 participants 8 participants
423.6  (182.80) 605.1  (670.60) 136.8  (108.33) 303.0  (274.85)
12.Secondary Outcome
Title Levels of BAL Biomarkers (Surfactant Protein and Clara Cell Secretory Protein) on Completion of Surgery
Hide 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.
Time Frame Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Nanograms per milliliter
Surfactant Protein D, n=5,9,5,8 Number Analyzed 5 participants 9 participants 5 participants 8 participants
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 Number Analyzed 5 participants 7 participants 5 participants 7 participants
3635.40  (2575.875) 2131.66  (3217.852) 1000.40  (1167.704) 1409.21  (2358.501)
13.Secondary Outcome
Title Change Over Time in PaO2/FiO2 Post-operatively on Day 2 Through to Day 4
Hide 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.
Time Frame Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Millimeters of Mercury
Day 2, n=5,8,5,6 Number Analyzed 5 participants 8 participants 5 participants 6 participants
-15.1  (171.84) -103.3  (87.24) 38.9  (312.28) -79.3  (199.85)
Day 3, n=5,8,5,5 Number Analyzed 5 participants 8 participants 5 participants 5 participants
-53.7  (120.35) -43.0  (179.64) -9.5  (325.46) -119.0  (148.67)
Day 4, n=5,8,5,5 Number Analyzed 5 participants 8 participants 5 participants 5 participants
-36.3  (139.18) -123.6  (68.14) -22.3  (342.46) -56.5  (123.31)
14.Secondary Outcome
Title Change Over Time in PVPI Post-operatively on Day 2 Through to Day 4
Hide 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.
Time Frame Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Ratio
Day 2, n=5,6,3,5 Number Analyzed 5 participants 6 participants 3 participants 5 participants
-0.22  (0.259) -0.27  (0.427) -0.50  (0.346) -0.42  (0.630)
Day 3, n=4,6,3,5 Number Analyzed 4 participants 6 participants 3 participants 5 participants
-0.20  (0.648) -0.23  (0.516) -0.30  (0.529) -0.32  (0.756)
Day 4, n=3,5,2,4 Number Analyzed 3 participants 5 participants 2 participants 4 participants
-0.40  (0.200) -0.24  (0.666) -0.20  (0.000) -0.08  (0.850)
15.Secondary Outcome
Title Change Over Time in EVLWI Post-operatively on Day 2 Through to Day 4
Hide 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.
Time Frame Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4
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PP1 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 10 5 8
Mean (Standard Deviation)
Unit of Measure: Millimeters per kilograms
Day 2, n=5,6,3,5 Number Analyzed 5 participants 6 participants 3 participants 5 participants
-0.033  (1.1203) -1.120  (2.4825) -0.694  (0.8710) 0.604  (1.3370)
Day 3, n=4,5,3,5 Number Analyzed 4 participants 5 participants 3 participants 5 participants
0.062  (1.2468) -0.190  (1.4762) -0.203  (2.3349) 0.755  (1.4801)
Day 4, n=3,5,2,4 Number Analyzed 3 participants 5 participants 2 participants 4 participants
-0.621  (0.2646) 0.828  (4.1772) 0.311  (1.9297) 1.981  (2.8449)
16.Secondary Outcome
Title Daily Sequential Organ Failure Assessment (SOFA) Scores on Day 2 Through to Day 4
Hide 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).
Time Frame Day 2 to Day 4
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PP 2 Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 11 6 8
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
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)
17.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0 to t])
Hide 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.
Time Frame 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)
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PK Population.
Arm/Group Title GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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 Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*picograms/milliliter
340505.15
(45.284%)
290102.64
(76.450%)
18.Secondary Outcome
Title Maximum Observed Concentration (Cmax)
Hide Description Blood samples for pharmacokinetic analysis of GSK2862277 were collected at the indicated time points.
Time Frame 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)
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PK Population.
Arm/Group Title GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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 Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picograms per milliliters
31123.58
(64.452%)
25469.14
(93.307%)
19.Secondary Outcome
Title Derived Pharmacokinetic Parameter- Half-life (t1/2) and Time of Occurrence of Cmax (Tmax)
Hide 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.
Time Frame 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)
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PK Population.
Arm/Group Title GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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 Number of Participants Analyzed 8 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
t1/2, n=0,0 Number Analyzed 0 participants 0 participants
Tmax, n=3,6 Number Analyzed 3 participants 6 participants
7.584
(11.4958%)
7.583
(11.4119%)
20.Secondary Outcome
Title Ratio of Total Protein Derived From BAL and Plasma Values
Hide 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.
Time Frame Day 1 (on completion of surgery)
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PP1 Population.
Arm/Group Title Placebo (Pooling BAL Collapsed and Ventilated Lungs) GSK2862277 26 mg (Pooling BAL Collapsed and Ventilated Lungs)
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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.
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 either collapsed lung BAL procedure or ventilated lung BAL procedure on Day 1.
Overall Number of Participants Analyzed 15 13
Median (Standard Deviation)
Unit of Measure: Ratio
0.005  (0.0020) 0.002  (0.0009)
21.Secondary Outcome
Title Number of Participants With Positive Immunogenicity Results Post-dosing
Hide 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.
Time Frame Day 8 and Day 31
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Safety Population.
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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.
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.
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 Number of Participants Analyzed 5 11 8 9
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
22.Secondary Outcome
Title BAL Concentrations of GSK2862277
Hide 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.
Time Frame Day 1 (on completion of surgery)
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PK Population.
Arm/Group Title GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
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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.
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 Number of Participants Analyzed 1 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter
11220.00 [1] 
(NA%)
74155.37
(377%)
[1]
Standard deviation could not calculated as a single participant was analyzed.
Time Frame 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 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.
 
Arm/Group Title Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Hide Arm/Group 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 BAL procedure on Day 1. 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. 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. 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.
All-Cause Mortality
Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)      0/11 (0.00%)      0/8 (0.00%)      0/9 (0.00%)    
Hide Serious Adverse Events
Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/5 (60.00%)      5/11 (45.45%)      5/8 (62.50%)      4/9 (44.44%)    
Blood and lymphatic system disorders         
Neutropenia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Pancytopenia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Splenic infarction  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Cardiac disorders         
Atrial fibrillation  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Gastrointestinal disorders         
Diaphragmatic hernia  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Small intestinal obstruction  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Gastrointestinal ischaemia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
General disorders         
Complication associated with device  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Infections and infestations         
Empyema  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Lower respiratory tract infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Pneumonia  1  0/5 (0.00%)  0 2/11 (18.18%)  2 2/8 (25.00%)  3 1/9 (11.11%)  1
Staphylococcal infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Injury, poisoning and procedural complications         
Failure to anastomose  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Anastomotic leak  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 2/9 (22.22%)  2
Iatrogenic injury  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Procedural pneumothorax  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Psychiatric disorders         
Delirium  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Aspiration  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Pleural effusion  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Pneumothorax spontaneous  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Pulmonary embolism  1  2/5 (40.00%)  2 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Chylothorax  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1
Diaphragmatic rupture  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Skin and subcutaneous tissue disorders         
Subcutaneous emphysema  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Vascular disorders         
Femoral artery embolism  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (BAL Collapsed Lung) Placebo (BAL Ventilated Lung) GSK2862277 26 mg (BAL Collapsed Lung) GSK2862277 26 mg (BAL Ventilated Lung)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/5 (100.00%)      10/11 (90.91%)      5/8 (62.50%)      8/9 (88.89%)    
Blood and lymphatic system disorders         
Anaemia  1  1/5 (20.00%)  1 3/11 (27.27%)  3 0/8 (0.00%)  0 0/9 (0.00%)  0
Anaemia folate deficiency  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Cardiac disorders         
Atrial fibrillation  1  2/5 (40.00%)  2 2/11 (18.18%)  2 1/8 (12.50%)  1 1/9 (11.11%)  2
Atrial flutter  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Bradycardia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Tachycardia  1  0/5 (0.00%)  0 1/11 (9.09%)  1 2/8 (25.00%)  2 0/9 (0.00%)  0
Eye disorders         
Diabetic retinopathy  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Diplopia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Visual acuity reduced  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Gastrointestinal disorders         
Constipation  1  2/5 (40.00%)  2 0/11 (0.00%)  0 2/8 (25.00%)  2 1/9 (11.11%)  1
Diarrhoea  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 1/9 (11.11%)  1
Dry mouth  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Haematochezia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Impaired gastric emptying  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Nausea  1  1/5 (20.00%)  1 1/11 (9.09%)  1 2/8 (25.00%)  2 1/9 (11.11%)  1
Vomiting  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  2 1/9 (11.11%)  1
Catheter site haematoma  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
General disorders         
Chest pain  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 2/9 (22.22%)  2
Fatigue  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Hypothermia  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Pyrexia  1  1/5 (20.00%)  1 3/11 (27.27%)  3 2/8 (25.00%)  3 1/9 (11.11%)  1
Catheter site haemorrhage  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Catheter site pain  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Catheter site discharge  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Complication associated with device  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Infections and infestations         
Injection site abscess  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Lower respiratory tract infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 3/8 (37.50%)  3 1/9 (11.11%)  1
Oral candidiasis  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Pneumonia  1  1/5 (20.00%)  1 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Pneumonia klebsiella  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Postoperative wound infection  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Urinary tract infection  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Staphylococcal bacteraemia  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Febrile infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Enterobacter sepsis  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Staphylococcal infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Wound infection staphylococcal  1  1/5 (20.00%)  1 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Klebsiella infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Device related infection  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Infectious pleural effusion  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Stoma site cellulitis  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Injury, poisoning and procedural complications         
Anaemia postoperative  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Postoperative hernia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Postoperative thoracic procedure complication  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Procedural complication  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Procedural hypotension  1  1/5 (20.00%)  1 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Endotracheal intubation complication  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Procedural pain  1  1/5 (20.00%)  1 1/11 (9.09%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0
Unintentional medical device removal  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Investigations         
Alanine aminotransferase increased  1  2/5 (40.00%)  2 2/11 (18.18%)  2 2/8 (25.00%)  2 2/9 (22.22%)  2
Blood albumin decreased  1  0/5 (0.00%)  0 1/11 (9.09%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0
Blood calcium decreased  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Blood creatine phosphokinase increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Blood creatinine increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Blood lactic acid increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Blood sodium decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Blood urea increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
C-reactive protein increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1
Electrocardiogram T wave inversion  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Gamma-glutamyltransferase increased  1  0/5 (0.00%)  0 3/11 (27.27%)  3 0/8 (0.00%)  0 0/9 (0.00%)  0
Glomerular filtration rate decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Haematocrit decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Haemoglobin decreased  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Lymphocyte count decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  2 0/9 (0.00%)  0
Monocyte count decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Neutrophil count decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  2 0/9 (0.00%)  0
Oxygen saturation decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  2 1/9 (11.11%)  1
Platelet count decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
PO2 decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Red blood cell count decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Reticulocyte count increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
White blood cell count decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
White blood cell count increased  1  0/5 (0.00%)  0 1/11 (9.09%)  1 1/8 (12.50%)  1 1/9 (11.11%)  1
Blood phosphorus decreased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 3/9 (33.33%)  3
Platelet count increased  1  0/5 (0.00%)  0 0/11 (0.00%)  0 2/8 (25.00%)  2 0/9 (0.00%)  0
Nasogastric output high  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Fungal test positive  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Blood alkaline phosphatase increased  1  0/5 (0.00%)  0 4/11 (36.36%)  4 1/8 (12.50%)  1 0/9 (0.00%)  0
Urine output decreased  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Electrocardiogram change  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Staphylococcus test positive  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 1/9 (11.11%)  1
Streptococcus test positive  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Escherichia test positive  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Klebsiella test positive  1  1/5 (20.00%)  2 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Nuclear magnetic resonance imaging spinal abnormal  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Metabolism and nutrition disorders         
Hyperkalaemia  1  0/5 (0.00%)  0 1/11 (9.09%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0
Hypoalbuminaemia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Hypocalcaemia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Hypoglycaemia  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Hypokalaemia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 2/8 (25.00%)  2 1/9 (11.11%)  1
Hypomagnesaemia  1  0/5 (0.00%)  0 1/11 (9.09%)  1 1/8 (12.50%)  1 1/9 (11.11%)  1
Hypophosphataemia  1  1/5 (20.00%)  1 1/11 (9.09%)  1 0/8 (0.00%)  0 1/9 (11.11%)  1
Hypoproteinaemia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Magnesium deficiency  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Mineral deficiency  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Joint swelling  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Musculoskeletal pain  1  2/5 (40.00%)  2 0/11 (0.00%)  0 1/8 (12.50%)  1 2/9 (22.22%)  2
Joint range of motion decreased  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Musculoskeletal chest pain  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastases to lymph nodes  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Nervous system disorders         
Dizziness  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Dizziness postural  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 2/9 (22.22%)  2
Hypoaesthesia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Presyncope  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Psychiatric disorders         
Agitation  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Confusional state  1  0/5 (0.00%)  0 1/11 (9.09%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0
Delirium  1  1/5 (20.00%)  1 0/11 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1
Renal and urinary disorders         
Dysuria  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Pollakiuria  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Urinary retention  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Urine odour abnormal  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Acute kidney injury  1  0/5 (0.00%)  0 2/11 (18.18%)  2 1/8 (12.50%)  1 0/9 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Atelectasis  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Cough  1  1/5 (20.00%)  1 1/11 (9.09%)  1 0/8 (0.00%)  0 2/9 (22.22%)  3
Hypoxia  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Lung consolidation  1  0/5 (0.00%)  0 1/11 (9.09%)  1 0/8 (0.00%)  0 0/9 (0.00%)  0
Pleural effusion  1  0/5 (0.00%)  0 0/11 (0.00%)  0 2/8 (25.00%)  2 0/9 (0.00%)  0
Pleuritic pain  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Pneumothorax  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Respiratory failure  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Respiratory tract irritation  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 2/9 (22.22%)  2
Tachypnoea  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0
Throat irritation  1  1/5 (20.00%)  1 3/11 (27.27%)  4 0/8 (0.00%)  0 0/9 (0.00%)  0
Wheezing  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Oropharyngeal discomfort  1  0/5 (0.00%)  0 0/11 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1
Oropharyngeal pain  1  0/5 (0.00%)  0 0/11 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1
Skin and subcutaneous tissue disorders         
Subcutaneous emphysema  1  1/5 (20.00%)  1 0/11 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0
Vascular disorders         
Hypertension  1  1/5 (20.00%)  1 1/11 (9.09%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0
Hypotension  1  2/5 (40.00%)  2 0/11 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02221037    
Other Study ID Numbers: 116341
2014-000643-33 ( EudraCT Number )
First Submitted: August 18, 2014
First Posted: August 20, 2014
Results First Submitted: June 27, 2018
Results First Posted: January 11, 2019
Last Update Posted: October 27, 2020