Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000643-33 | EudraCT Number |
Not provided
Not provided
Not provided
The study was terminated on the basis that protocol defined stopping criteria had been met.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Lung injury in patients undergoing oesophagectomy may occur during surgery (peri-operatively) as a result of One Lung Ventilation (OLV) and/or during the immediate post-operative period when patients receive intensive care. This is reinforced by the observation that physiological markers of lung injury are most elevated immediately after completion of surgery, and the development of clinical Acute Respiratory Distress Syndrome (ARDS)occurs immediately post-operatively (within 72 hours of surgery), with the majority of cases reported 24-48 hours after completion of surgery. This study is designed to investigate the impact of pre-operative administration of GSK2862277 on biological and physiological markers of lung injury in patients undergoing surgical resection of oesophageal cancer in order to achieve optimal exposure at the site of injury following OLV and lung deflation. This study is a randomized placebo controlled, double-blind, multi-centre, single dose parallel group, design. There will be two treatment groups comprising one active and one placebo arm with approximately 40 patients per group. Patients enrolled in the study will be scheduled to undergo planned/elective trans-thoracic surgery for oesophagectomy. The primary endpoint for this study is the change in pulmonary vascular permeability index (PVPI) from pre-surgical levels to the end of surgery. GSK2862277 will be administered as an orally inhaled aerosol (single nebulized dose) over approximately 3 to 5 minutes (min) 1-3 hours prior to surgery. Subject will be monitored daily until discharge and followed up till day 28.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2862277 | Experimental | GSK2862277 will be administered as single orally inhaled aerosol over approximately 3 to 5 minutes; approximately 1-3 hours prior to the subjects scheduled surgery, before the initiation of pre-operative procedures. After surgery subject will undergo either ventilated or collapsed lung BAL procedure. Regular assessments will be conducted until the time of patient discharge. Subjects will be followed up as outpatients at Day 28 |
|
| Placebo | Placebo Comparator | Placebo will be administered as single orally inhaled aerosol over approximately 3 to 5 minutes; approximately 1-3 hours prior to the subjects scheduled surgery, before the initiation of pre-operative procedures. After surgery subject will be undergo either ventilated or collapsed lung BAL procedure. Regular assessments will conducted until the time of patient discharge. Subjects will be followed up as outpatients at Day 28 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2862277 | Drug | It is available as 26 milligrams (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 nebulisation as approximately 3-5 min and will be administered using "Pari eFlow with s30 mesh" device. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Adjusted Change in Pulmonary Vascular Permeability Index (PVPI) on Completion of Surgery | 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). | Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery) |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Adjusted Change in EVLWI on Completion of Surgery | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Criteria Based Upon Medical Histories
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cottingham | Yorkshire | HU16 5JQ | United Kingdom | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32467417 | Background | Ryan J, Bayliffe AI, McAuley DF, Yeung J, Thickett DR, Howells PA, O'Donnell C, Vassallo AM, Wright TJ, McKie E, Hardes K, Summers C, Shields MO, Powley W, Wilson R, Lazaar AL, Fowler A, Perkins GD. A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study. Eur J Anaesthesiol. 2020 Nov;37(11):1014-1024. doi: 10.1097/EJA.0000000000001245. |
Not provided
Not provided
IPD for this study is available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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).
The study was conducted at 8 centers in the United Kingdom from 28-Apr-2015 to 28-Jun-2017.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (BAL Collapsed Lung) | Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung broncho-alveolar lavage (BAL) procedure on Day 1. |
| FG001 | Placebo (BAL Ventilated Lung) | Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. |
| FG002 | GSK2862277 26 mg (BAL Collapsed Lung) | Eligible participants received a single dose of GSK2862277 26 milligrams (mg) on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. |
| FG003 | GSK2862277 26 mg (BAL Ventilated Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population which comprised of all participants who received at least one complete dose of study treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (BAL Collapsed Lung) | Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Baseline Adjusted Change in Pulmonary Vascular Permeability Index (PVPI) on Completion of Surgery | 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). | PP1 Population. | Posted | Mean | Standard Deviation | Ratio | Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery) |
|
Serious adverse events and non-serious adverse events were collected from start of the study medication (Day 1) to Follow-up (Day 31)
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (BAL Collapsed Lung) | Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 23, 2016 | Jun 15, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 17, 2015 | Jun 15, 2018 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D055370 | Lung Injury |
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D013898 | Thoracic Injuries |
| D014947 | Wounds and Injuries |
Not provided
Not provided
| ID | Term |
|---|---|
| C000605830 | GSK2862277 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | It is a clear, colorless to pale yellow liquid, will be administered in volume to match active dose as solution for inhalation with duration of nebulisation as approximately 3-5 min and will be administered using "Pari eFlow with s30 mesh" device. |
|
| Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery) |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | 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. | Up to Day 31 |
| Number of Participants With Hematology Abnormalities of Potential Clinical Importance | 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. | Up to Day 8 |
| Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | 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. | Up to Day 8 |
| Number of Participants With Abnormal Urinalysis Parameters | 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. | Day 1 (pre-dose) and Day 8 |
| Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance | 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. | Days 1, 2, 4 and 8 |
| Number of Participants With Vital Signs of Potential Clinical Importance | 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. | Up to Day 31 |
| Baseline Adjusted Change in PaO2/FiO2 on Completion of Surgery | 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. | Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery) |
| Levels of BAL Biomarkers on Completion of Surgery | 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. | Day 1 (on completion of surgery) |
| Levels of BAL Biomarkers (C-reactive Protein and Total Proteins) on Completion of Surgery | 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. | Day 1 (on completion of surgery) |
| Levels of BAL Biomarkers (Surfactant Protein and Clara Cell Secretory Protein) on Completion of Surgery | 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. | Day 1 (on completion of surgery) |
| Change Over Time in PaO2/FiO2 Post-operatively on Day 2 Through to Day 4 | 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. | Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4 |
| Change Over Time in PVPI Post-operatively on Day 2 Through to Day 4 | 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. | Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4 |
| Change Over Time in EVLWI Post-operatively on Day 2 Through to Day 4 | 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. | Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4 |
| Daily Sequential Organ Failure Assessment (SOFA) Scores on Day 2 Through to Day 4 | 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). | Day 2 to Day 4 |
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0 to t]) | 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. | 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) |
| Maximum Observed Concentration (Cmax) | Blood samples for pharmacokinetic analysis of GSK2862277 were collected at the indicated time points. | 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) |
| Derived Pharmacokinetic Parameter- Half-life (t1/2) and Time of Occurrence of Cmax (Tmax) | 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. | 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) |
| Ratio of Total Protein Derived From BAL and Plasma Values | 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. | Day 1 (on completion of surgery) |
| Number of Participants With Positive Immunogenicity Results Post-dosing | 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. | Day 8 and Day 31 |
| BAL Concentrations of GSK2862277 | 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. | Day 1 (on completion of surgery) |
| Belfast |
| BT9 7AB |
| United Kingdom |
| GSK Investigational Site | Birmingham | B15 2TH | United Kingdom |
| GSK Investigational Site | Birmingham | B9 5SS | United Kingdom |
| GSK Investigational Site | Cambridge | CB2 0QQ | United Kingdom |
| GSK Investigational Site | Middlesbrough | TS4 3BU | United Kingdom |
| Placebo (BAL Ventilated Lung) |
Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. |
| BG002 | GSK2862277 26 mg (BAL Collapsed Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. |
| BG003 | GSK2862277 26 mg (BAL Ventilated Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. |
| OG001 | Placebo (BAL Ventilated Lung) | Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. |
| OG002 | GSK2862277 26 mg (BAL Collapsed Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. |
| OG003 | GSK2862277 26 mg (BAL Ventilated Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. |
|
|
| Secondary | Baseline Adjusted Change in EVLWI on Completion of Surgery | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Milliliters per kilograms | Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery) |
|
|
|
| Secondary | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | 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. | Safety Population. | Posted | Number | Participants | Up to Day 31 |
|
|
|
| Secondary | Number of Participants With Hematology Abnormalities of Potential Clinical Importance | 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. | Safety Population. | Posted | Number | Participants | Up to Day 8 |
|
|
|
| Secondary | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | 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. | Safety Population. | Posted | Number | Participants | Up to Day 8 |
|
|
|
| Secondary | Number of Participants With Abnormal Urinalysis Parameters | 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. | Safety Population. | Posted | Number | Participants | Day 1 (pre-dose) and Day 8 |
|
|
|
| Secondary | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance | 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. | Safety Population. | Posted | Number | Participants | Days 1, 2, 4 and 8 |
|
|
|
| Secondary | Number of Participants With Vital Signs of Potential Clinical Importance | 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. | Safety Population. | Posted | Number | Participants | Up to Day 31 |
|
|
|
| Secondary | Baseline Adjusted Change in PaO2/FiO2 on Completion of Surgery | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Millimiters of Mercury | Baseline (Day 1 [immediately prior to start of surgery]) and Day 1 (on completion of surgery) |
|
|
|
| Secondary | Levels of BAL Biomarkers on Completion of Surgery | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Picograms per milliliter | Day 1 (on completion of surgery) |
|
|
|
| Secondary | Levels of BAL Biomarkers (C-reactive Protein and Total Proteins) on Completion of Surgery | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Milligrams per Liter | Day 1 (on completion of surgery) |
|
|
|
| Secondary | Levels of BAL Biomarkers (Surfactant Protein and Clara Cell Secretory Protein) on Completion of Surgery | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Nanograms per milliliter | Day 1 (on completion of surgery) |
|
|
|
| Secondary | Change Over Time in PaO2/FiO2 Post-operatively on Day 2 Through to Day 4 | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Millimeters of Mercury | Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4 |
|
|
|
| Secondary | Change Over Time in PVPI Post-operatively on Day 2 Through to Day 4 | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Ratio | Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4 |
|
|
|
| Secondary | Change Over Time in EVLWI Post-operatively on Day 2 Through to Day 4 | 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. | PP1 Population. | Posted | Mean | Standard Deviation | Millimeters per kilograms | Baseline (Day 1 [immediately prior to start of surgery]) to Days 2, 3 and 4 |
|
|
|
| Secondary | Daily Sequential Organ Failure Assessment (SOFA) Scores on Day 2 Through to Day 4 | 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). | PP 2 Population. | Posted | Mean | Standard Deviation | Scores on a Scale | Day 2 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]) | 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*picograms/milliliter | 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) |
|
|
|
| Secondary | Maximum Observed Concentration (Cmax) | Blood samples for pharmacokinetic analysis of GSK2862277 were collected at the indicated time points. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliters | 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) |
|
|
|
| Secondary | Derived Pharmacokinetic Parameter- Half-life (t1/2) and Time of Occurrence of Cmax (Tmax) | 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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) |
|
|
|
| Secondary | Ratio of Total Protein Derived From BAL and Plasma Values | 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. | PP1 Population. | Posted | Median | Standard Deviation | Ratio | Day 1 (on completion of surgery) |
|
|
|
| Secondary | Number of Participants With Positive Immunogenicity Results Post-dosing | 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. | Safety Population. | Posted | Number | Participants | Day 8 and Day 31 |
|
|
|
| Secondary | BAL Concentrations of GSK2862277 | 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms per milliliter | Day 1 (on completion of surgery) |
|
|
|
| 0 |
| 5 |
| 3 |
| 5 |
| 5 |
| 5 |
| EG001 | Placebo (BAL Ventilated Lung) | Eligible participants received a single dose of matching placebo on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. | 0 | 11 | 5 | 11 | 10 | 11 |
| EG002 | GSK2862277 26 mg (BAL Collapsed Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent collapsed lung BAL procedure on Day 1. | 0 | 8 | 5 | 8 | 5 | 8 |
| EG003 | GSK2862277 26 mg (BAL Ventilated Lung) | Eligible participants received a single dose of GSK2862277 26 mg on Day 1 via oral inhalation route over approximately 3 to 5 minutes; approximately 1 to 3 hours prior to scheduled surgery. After surgery, participants in this arm underwent ventilated lung BAL procedure on Day 1. | 0 | 9 | 4 | 9 | 8 | 9 |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Splenic infarction | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diaphragmatic hernia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gastrointestinal ischaemia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Complication associated with device | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Empyema | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Failure to anastomose | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Anastomotic leak | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Iatrogenic injury | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Procedural pneumothorax | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chylothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diaphragmatic rupture | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Femoral artery embolism | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anaemia folate deficiency | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atrial flutter | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diabetic retinopathy | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypothermia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site haemorrhage | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site haematoma | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site discharge | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Complication associated with device | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Injection site abscess | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonia klebsiella | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Febrile infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Enterobacter sepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Wound infection staphylococcal | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Klebsiella infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Infectious pleural effusion | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Stoma site cellulitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Anaemia postoperative | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Postoperative hernia | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Postoperative thoracic procedure complication | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Procedural hypotension | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Endotracheal intubation complication | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Unintentional medical device removal | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood lactic acid increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Electrocardiogram T wave inversion | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| PO2 decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Reticulocyte count increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Nasogastric output high | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Fungal test positive | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Urine output decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Electrocardiogram change | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Staphylococcus test positive | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Streptococcus test positive | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Escherichia test positive | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Klebsiella test positive | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Nuclear magnetic resonance imaging spinal abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Magnesium deficiency | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Mineral deficiency | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Metastases to lymph nodes | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Urine odour abnormal | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lung consolidation | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Respiratory tract irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
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.
| D012120 |
| Respiration Disorders |
| SAE |
|
| Urine glucose: Day 1 (pre-dose): 1+ |
|
| Urine glucose: Day 1 (pre-dose): 2+ |
|
| Urine glucose: Day 1 (pre-dose): 3+ |
|
| Urine glucose: Day 8: Trace |
|
| Urine glucose: Day 8: 1+ |
|
| Urine glucose: Day 8: 2+ |
|
| Urine glucose: Day 8: 3+ |
|
| Urine ketones: Day 1 (pre-dose): Trace |
|
| Urine ketones: Day 1 (pre-dose): 1+ |
|
| Urine ketones: Day 1 (pre-dose): 2+ |
|
| Urine ketones: Day 1 (pre-dose): 3+ |
|
| Urine ketones: Day 8: Trace |
|
| Urine ketones: Day 8: 1+ |
|
| Urine ketones: Day 8: 2+ |
|
| Urine ketones: Day 8: 3+ |
|
| Urine occult blood: Day 1 (pre-dose): Trace |
|
| Urine occult blood: Day 1 (pre-dose): 1+ |
|
| Urine occult blood: Day 1 (pre-dose): 2+ |
|
| Urine occult blood: Day 1 (pre-dose): 3+ |
|
| Urine occult blood: Day 8: Trace |
|
| Urine occult blood: Day 8: 1+ |
|
| Urine occult blood: Day 8: 2+ |
|
| Urine occult blood: Day 8: 3+ |
|
| Urine protein: Day 1 (pre-dose): Trace |
|
| Urine protein: Day 1 (pre-dose): 1+ |
|
| Urine protein: Day 1 (pre-dose): 2+ |
|
| Urine protein: Day 1 (pre-dose): 3+ |
|
| Urine protein: Day 8: Trace |
|
| Urine protein: Day 8: 1+ |
|
| Urine protein: Day 8: 2+ |
|
| Urine protein: Day 8: 3+ |
|
|
| STNFR I, Total, n=5,9,5,8 |
|
|
| Tumor necrosis factor alpha, n=5,9,5,7 |
|
|
| Interleukin 6, n=5,9,5,8 |
|
|
| Interleukin 8, n=5,9,5,8 |
|
|
| Interleukin 1 beta, n=5,9,5,8 |
|
|
| Monocyte chemotactic protein-1, n=5,9,5,8 |
|
|
| Macrophage inflammatory protein 1 alpha, n=5,9,5,8 |
|
|
| Macrophage inflammatory protein 1 beta, n=5,9,5,8 |
|
|
| Interleukin 10, n=5,9,5,8 |
|
|
| sRAGE products, n=5,9,5,8 |
|
|
|
| Total proteins, n=5,10,5,8 |
|
|
|
| Clara cell secretory protein, n=5,7,5,7 |
|
|
|
| Day 3, n=5,8,5,5 |
|
|
| Day 4, n=5,8,5,5 |
|
|
|
| Day 3, n=4,6,3,5 |
|
|
| Day 4, n=3,5,2,4 |
|
|
|
| Day 3, n=4,5,3,5 |
|
|
| Day 4, n=3,5,2,4 |
|
|
| Day 3 |
|
| Day 4 |
|
|