Clincosm LogoSign in Get a demo

The Safety, Tolerability, PK and PD of GSK2586881 in Patients With Acute Lung Injury

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01597635
Collaborator
(none)
44
Enrollment
19
Locations
2
Arms
25.1
Duration (Months)
2.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an early phase (phase IIa), randomized, multi-center study in subjects with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The purpose of this study is to investigate the safety of GSK2586881 and to determine what effects it has on people with Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS).

The study has two parts: Part A will be an open-label investigation in five subjects. Part B will be a double-blind, placebo controlled investigation and will involve approximately 60 subjects.

Condition or Disease Intervention/Treatment Phase
  • Drug: Dose 1 GSK2586881
  • Drug: Dose 2 GSK2586881
  • Drug: Dose 3 GSK2586881
  • Drug: Dose 4 GSK2586881
  • Drug: Placebo (saline)
 Phase 2

Detailed Description

The acute respiratory distress syndrome (ARDS) is a form of severe acute lung injury (ALI) characterized by hypoxemic respiratory failure (the lungs are unable to absorb oxygen to the arterial blood) and non-cardiogenic pulmonary edema (accumulation of fluid in the lungs). The syndrome may be caused by direct or indirect injury to the lungs. It is associated with a mortality rate of up to 40-50%. There are no marketed pharmacologic therapies for this devastating syndrome.

This study aims to assess the safety, tolerability and pharmacodynamics of GSK2586881, a recombinant human angiotensin converting enzyme type 2 (rhACE2).

ACE2 is involved in the Renin-Angiotensin System (RAS), which controls blood pressure, electrolytes and intravascular fluid volume. A key function of rhACE2 is believed to be the cleavage of Angiotensin II (Ang II) to Ang (1-7), which have opposing physiological roles. Elevated levels of Ang II are associated with vasoconstriction, inflammation, fibrosis, vascular leak, and sodium absorption. Ang (1-7) appears to be a counterregulatory protein in the RAS; associated with vasodilation, anti-proliferation, antiinflammation, and reduced vascular leak. It has been observed that levels of Ang II are increased in humans with ALI/ ARDS. It is expected that the reduction of Ang II should have a positive impact on ALI and ARDS.

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Two Part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586881 in Patients With Acute Lung Injury
Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Oct 1, 2014
Actual Study Completion Date :
Oct 6, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A

4 increasing doses of GSK2586881 given over 2 days

Drug: Dose 1 GSK2586881
Low dose GSK2586881 administered intravenously

Drug: Dose 2 GSK2586881
Medium dose GSK2586881 administered intravenously

Drug: Dose 3 GSK2586881
Medium-High dose GSK2586881 administered intravenously

Drug: Dose 4 GSK2586881
High dose GSK2586881 administered intravenously
Experimental: Part B

Repeat Medium-High dose of GSK2586881 (or placebo) over 3 days

Drug: Dose 3 GSK2586881
Medium-High dose GSK2586881 administered intravenously

Drug: Placebo (saline)
Administered intravenously to match intervention

Outcome Measures

Primary Outcome Measures

  1. Heart Rate Assessments Upto Day 7 (Part B) [Up to Day 7]

    Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.

  2. Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) [Up to Day 7]

    Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.

  3. Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) [Up to Day 7]

    Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  4. Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) [Up to Day 7]

    Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  5. Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) [Up to Day 7]

    Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  6. Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) [Up to Day 7]

    Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  7. Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) [Up to Day 7]

    Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  8. Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) [Up to Day 7]

    Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  9. Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) [Up to Day 7]

    Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  10. Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) [Up to Day 7]

    Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  11. Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) [Up to Day 7]

    Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  12. Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) [Up to Day 7]

    Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  13. Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) [Up to Day 7]

    Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.

  14. Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A) [Up to Day 7]

    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

  15. Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) [Up to Day 7]

    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Secondary Outcome Measures

  1. Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) [Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2)]

    Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part A

  2. Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) [Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3)]

    Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part B.

  3. Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A) [Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours]

    Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.

  4. Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B) [Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours]

    Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.

  5. Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) [Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).]

    Renin-angiotensin system cascade biomarkers included Ang II and Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.

  6. Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) [Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).]

    Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours on Day 1 and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.

  7. Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) [0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.]

    Renin-angiotensin system cascade biomarkers included Ang II, Ang (1-7) and Ang (1-5). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

  8. Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B) [0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.]

    Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-5) and Ang II/Ang (1-7) and). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

  9. Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) [0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7]

    Measures of oxygenation included PEEP the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration, peak ventilator pressure highest level of pressure applied to the lungs during inhalation and plateau ventilatory pressure the pressure applied to small airways and alveoli measured during an inspiratory pause on the ventilator. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.

  10. Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B) [0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7]

    Measure of oxygenation included PaO2/FiO2 ratio defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen by pulse oximeter a device that measured the oxygen saturation of arterial blood in a participant by utilizing a sensor attached typically to a finger, toe, or ear to determine the percentage of oxyhemoglobin in blood pulsating through a network of capillaries. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.

  11. Measure of Oxygenation Index Upto Day 7 (Part B) [0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7]

    Oxygenation index was defined as calculation used in intensive care medicine to measure the fraction of inspired oxygen (FiO2) and its usage within the body and was computed using the equation Oxygenation Index= FiO2 x Mean Airway Pressure/Pao2. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.

  12. Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B) [Upto Day 3]

    The RIFLE score is made up of the glomerular filtration rate criteria (GFRC) and urine output criteria (UOC) and is defined as Risk (Serum Creatinine x 1.5 or GFR decrease > 25%-GFRC and < 0.5 milliliter/kilograms/hour [ml/kg/hour] x 6 hours-UOC), Injury (Serum Creatinine x 2 or GFR decrease > 50%-GFRC and < 0.5 ml/kg/hour x 12 hours), Failure (Serum Creatinine x 3, or GFR decrease > 75% [F=Failure] or Serum Creatinine >=4 milligrams/deciliter [mg/dl] with an acute rise > 0.5 mg/dl [Fc=Failure acute on chronic] and < 0.3 ml/kg/hour x 24 hours, or anuria x 12 hours [Fo=Failure oligouria]). Due to the duration of this study it was not possible to be calculate the designated RIFLE class Loss and RIFLE class End-stage kidney disease. Data has been presented for rifle score total, rifle score GFR and rifle score urine. Abbreviations NAKI= No acute kidney injury, R=risk, I=injury, MISS= Unable to derive score.

  13. Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) [Day 4 and Day 7]

    The SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). The score ranges from 0-24. 0 (normal) to 4 (high degree of dysfunction) is given for each organ system, with a higher score indicating greater severity. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.

  14. Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B) [12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5]

    Serum inflammatory biomarkers included CXCL-8 [IL-8], IL-6, markers of neutrophil activation included (e.g. myeloperoxidase [MPO]), markers of lung epithelial cell injury included receptor for advanced glycation end-products [RAGE], Angiopoietin 2, along with rennin, aldosterone levels. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

  15. Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) [12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5]

    Serum inflammatory biomarker included CRP. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

  16. Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B) [12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5]

    Markers of lung epithelial cell injury included CCP16 and SP-D. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.

  17. Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) [Follow-up (Day 14) and follow-up (Day 28)]

    Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.

  18. Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) [Follow-up (Day 14 )and follow-up (Day 28)]

    Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Male or female, 18 - 80 years of age (inclusive)

  • Diagnosis of ALI with acute onset of PaO2/FiO2 ratio less than or equal to 300, and bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. The infiltrates may be patchy, diffuse, homogeneous, or asymmetric, and requirement for positive pressure ventilation via an endotracheal tube, and no clinical evidence of left atrial hypertension

  • Cause of ALI thought to be associated with infection, sepsis, pneumonia, aspiration, or similar as judged by the PI and/or medical monitor

  • The subject must be randomized into the study within 48 hours from the time of diagnosis of ALI

  • Period of hemodynamic stability (e.g. 4-6 hours) prior to the initiation of study treatment not requiring resuscitative measures with stable pressor requirements. In this study low-dose arginine vasopressin is not considered a pressor, and is permitted in Parts A and B.

  • If mechanically ventilated, duration of mechanical ventilation must be less than 72 hours before dosing begins

  • BMI within the range 19.0 - 38.0 kg/m2 inclusive

  • The subject or legal decision maker is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

  • QTcB or QTcF less than 450 msec; or QTc less than 480 msec in subjects with Bundle Branch Block.

  • Alanine aminotransferase (ALT) less than 5 x Upper Limit of Normal (ULN); bilirubin less than or equal to 1.5 x ULN.

Exclusion Criteria:

  • Subjects whose clinical condition is deteriorating rapidly or any subject for whom the investigator does not consider there is a reasonable expectation that they will be able to complete the study.

  • Known positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody

  • Current or chronic history of liver disease (Child Pugh score of greater than or equal to 10), or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

  • Known history of substance abuse or alcohol abuse, within 6 months of the study causing chronic liver disease such as cirrhosis, chronic ascites or portal hypertension, or known evidence of withdrawal syndrome within the past 6 months.

  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

  • Inability to discontinue use of Angiotensin converting enzyme type 1 inhibitors or Angiotensin receptor blockers.

  • Patients requiring high doses of loop diuretics with significant intravascular volume depletion, as assessed clinically

  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation

  • Pregnant females as determined by positive serum or urine hCG test prior to dosing

  • Lactating females

  • Unwillingness or inability to follow the procedures outlined in the protocol

  • Subject is legally incapacitated (e.g. a prisoner)

  • History of sensitivity to heparin or heparin-induced thrombocytopenia

  • Unstable Hemoglobin (Hb less than 7) at time of drug infusion

  • Malignancy or other irreversible condition for which 6 month mortality is estimated to be greater than 50%

  • Arterial blood pH less than 7.1 or serum HCO3 - less than 15 (if ABG not available) before infusion is started

  • Known severe chronic respiratory disease:

  • known Forced Expiratory Volume in 1 second (FEV1)/ Forced Vital Capacity (FVC) less than 45% predicted, or

  • known chronic hypercapnia (PaCO2 greater than 45 mmHg) or chronic hypoxemia (PaO2 less than 55 mmHg) on FiO2 =0.21, or

  • known FEV1 less than 15 ml/kg (e.g. 1L for 70 kg person), or

  • known radiographic evidence of chronic interstitial infiltration, or

  • known hospitalization within the past six months for respiratory failure (PaCO2 greater than 50 mmHg or PaO2 less than 55 mmHg, or oxygen saturation less than 88% on FiO2 = 0.21), or

  • known chronic restrictive, obstructive, neuromuscular, chest wall, or pulmonary vascular disease resulting in severe exercise restriction

  • Known history of neuromuscular disease that would affect time on mechanical ventilation or impairs ability to ventilate spontaneously

  • Vasculitis with diffuse alveolar hemorrhage

  • Lung transplantation

  • Pre-existing renal failure on hemodialysis or peritoneal dialysis requiring renal replacement therapy

  • A patient will be excluded if in the judgement of the Principle Investigator or GSK medical monitor their participation could jeopardize the health of the subject or the integrity of the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Sacramento California United States 95817
2 GSK Investigational Site Chicago Illinois United States 60611
3 GSK Investigational Site Springfield Massachusetts United States 01199
4 GSK Investigational Site Ann Arbor Michigan United States 48109
5 GSK Investigational Site New York New York United States 10003
6 GSK Investigational Site Durham North Carolina United States 27710
7 GSK Investigational Site Greensboro North Carolina United States 27403
8 GSK Investigational Site Winston-Salem North Carolina United States 27517
9 GSK Investigational Site Columbus Ohio United States 43215
10 GSK Investigational Site Portland Oregon United States 97239
11 GSK Investigational Site Philadelphia Pennsylvania United States 19104
12 GSK Investigational Site Philadelphia Pennsylvania United States 19107
13 GSK Investigational Site Charleston South Carolina United States 29425
14 GSK Investigational Site Vancouver British Columbia Canada V5Z 1M9
15 GSK Investigational Site Vancouver British Columbia Canada V6Z 1Y6
16 GSK Investigational Site Halifax Nova Scotia Canada B3H 2Y9
17 GSK Investigational Site Kingston Ontario Canada K7L 2V7
18 GSK Investigational Site Greenfield Park Quebec Canada J4V 2H1
19 GSK Investigational Site Sainte-Foy Quebec Canada G1V 4G5

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01597635
Other Study ID Numbers:
  • 114622
First Posted:
May 14, 2012
Last Update Posted:
Sep 28, 2017
Last Verified:
Aug 1, 2017
Keywords provided by GlaxoSmithKline
rhACE2
Acute Respiratory Distress Syndrome (ARDS)
Acute Lung Injury
GSK2586881
critical care
Additional relevant MeSH terms:
Lung Injury
Acute Lung Injury
Wounds and Injuries

Study Results

Participant Flow

Recruitment Details This study was conducted across 5 centers in United States and 5 centers in Canada from 20 September 2012 to 06 October 2014.
Pre-assignment Detail A total of 46 participants were randomized for this study of which 44 participants (5 participants in Part A and 39 participants in Part B) received at least one dose of study medication.
Arm/Group Title Part A Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kilograms [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days. Eligible participants received intravenous matching placebo (saline solution) twice daily (BID) as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Period Title: Part A
STARTED 5 0 0
COMPLETED 2 0 0
NOT COMPLETED 3 0 0
Period Title: Part A
STARTED 0 20 19
COMPLETED 0 14 15
NOT COMPLETED 0 6 4

Baseline Characteristics

Arm/Group Title Part A Part B (Placebo BID) Part B (GSK2586881 BID) Total
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days. Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days. Total of all reporting groups
Overall Participants 5 20 19 44
Age, Customized (Count of Participants)
18-80 years
5
100%
20
100%
19
100%
44
100%
Sex: Female, Male (Count of Participants)
Female
2
40%
7
35%
6
31.6%
15
34.1%
Male
3
60%
13
65%
13
68.4%
29
65.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
1
5%
0
0%
1
2.3%
Asian
0
0%
1
5%
1
5.3%
2
4.5%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
1
5%
0
0%
1
2.3%
White
5
100%
17
85%
18
94.7%
40
90.9%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Heart Rate Assessments Upto Day 7 (Part B)
Description Vital sign included heart rate. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population was defined as all participants in Part B who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Heart rate on Day 1 at Pre-dose
87.4
(16.32)
97.7
(16.25)
Heart rate on Day 1 at 0.5 hours
87.9
(17.08)
95.3
(15.10)
Heart rate on Day 1 at 2 hours
88.8
(18.22)
94.7
(17.59)
Heart rate on Day 1 at 6 hours
90.0
(18.03)
96.5
(18.58)
Heart rate on Day 1 at 12 hours
87.6
(20.60)
97.1
(18.46)
Heart rate on Day 2 at 0 hours
92.2
(19.02)
93.4
(16.98)
Heart rate on Day 3 at 0 hours
93.3
(19.20)
97.7
(14.11)
Heart rate on Day 3 at 0.5 hours
91.7
(16.29)
97.2
(12.81)
Heart rate on Day 3 at 2 hours
93.2
(16.51)
95.2
(13.31)
Heart rate on Day 3 at 6 hours
93.2
(16.63)
97.5
(14.44)
Heart rate on Day 3 at 12 hours
93.8
(20.12)
93.6
(16.08)
Heart rate on Day 3 at 18 hours
98.1
(19.34)
88.9
(15.69)
Heart rate on Day 3 at 24 hours
90.8
(15.46)
95.1
(13.25)
Heart rate at follow-up Day 7
91.6
(19.06)
94.2
(15.17)
2. Primary Outcome
Title Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)
Description Vital sign included systolic blood pressure and diastolic blood pressure. Assessments were performed at Pre-dose, 0.5 hours, 2 hours, 6 hours and 12 hours on Day 1, 0 hours on Day 2 at 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours on Day 3 and at follow-up on Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Diastolic blood pressure on Day 1 at Pre-dose
64.7
(12.86)
53.9
(10.36)
Diastolic blood pressure on Day 1 at 0.5 hours
64.4
(13.75)
54.3
(11.39)
Diastolic blood pressure on Day 1 at 2 hours
64.4
(12.59)
54.8
(9.60)
Diastolic blood pressure on Day 1 at 6 hours
63.4
(12.08)
57.1
(9.21)
Diastolic blood pressure on Day 1 at 12 hours
64.3
(12.78)
57.6
(10.05)
Diastolic blood pressure on Day 2 at 0 hours
67.0
(15.17)
57.0
(10.22)
Diastolic blood pressure on Day 3 at 0 hours
63.9
(14.50)
62.7
(14.03)
Diastolic blood pressure on Day 3 at 0.5 hours
65.6
(13.21)
61.1
(12.83)
Diastolic blood pressure on Day 3 at 2 hours
65.2
(10.34)
58.1
(11.20)
Diastolic blood pressure on Day 3 at 6 hours
65.2
(13.83)
62.2
(16.59)
Diastolic blood pressure on Day 3 at 12 hours
70.0
(16.40)
60.6
(13.20)
Diastolic blood pressure on Day 3 at 18 hours
73.2
(16.31)
61.8
(10.50)
Diastolic blood pressure on Day 3 at 24 hours
66.4
(15.19)
61.1
(13.06)
Diastolic blood pressure on follow-up Day 7
66.4
(11.58)
62.7
(8.52)
Systolic blood pressure on Day 1 at Pre-dose
122.0
(18.97)
106.1
(12.68)
Systolic blood pressure on Day 1 at 0.5 hours
118.8
(20.01)
105.7
(12.66)
Systolic blood pressure on Day 1 at 2 hours
122.9
(14.85)
107.5
(20.49)
Systolic blood pressure on Day 1 at 6 hours
121.6
(17.80)
118.7
(16.41)
Systolic blood pressure on Day 1 at 12 hours
122.9
(21.88)
116.9
(24.33)
Systolic blood pressure on Day 2 at 0 hours
131.6
(23.68)
114.8
(18.94)
Systolic blood pressure on Day 3 at 0 hours
124.4
(16.32)
125.2
(23.70)
Systolic blood pressure on Day 3 at 0.5 hours
127.1
(15.76)
121.9
(23.60)
Systolic blood pressure on Day 3 at 2 hours
125.2
(14.77)
118.5
(20.87)
Systolic blood pressure on Day 3 at 6 hours
127.8
(19.01)
118.5
(19.60)
Systolic blood pressure on Day 3 at 12 hours
130.2
(21.95)
123.2
(24.61)
Systolic blood pressure on Day 3 at 18 hours
137.5
(23.92)
129.0
(17.45)
Systolic blood pressure on Day 3 at 24 hours
128.8
(20.43)
130.3
(24.97)
Systolic blood pressure on follow-up Day 7
129.1
(22.22)
129.9
(17.92)
3. Primary Outcome
Title Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)
Description Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTCU and RR intervals. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
PR interval on Day 1,Pre-dose
136.8
(24.19)
139.0
(25.09)
PR interval on Day 3,12 hours
128.5
(42.09)
149.3
(19.76)
PR interval at follow-up
140.4
(17.81)
144.8
(20.73)
QRS duration on Day 1,Pre-dose
98.0
(9.27)
95.5
(16.62)
QRS duration on Day 3,12 hours
82.8
(8.66)
98.8
(15.86)
QRS duration at follow-up Day 7
84.4
(9.01)
88.6
(16.86)
Uncorrected QT interval on Day 1,Pre-dose
350.0
(27.96)
357.5
(44.13)
Uncorrected QT interval on Day 3,12 hours
357.8
(48.90)
369.8
(33.92)
Uncorrected QT interval at follow-up Day 7
354.3
(37.12)
377.5
(49.46)
Corrected QT interval(Basett) on Day 1,Pre-dose
463.0
(NA)
469.4
(66.08)
Corrected QT interval(Basett) on Day 3,12 hours
438.9
(13.02)
468.9
(41.59)
Corrected QT interval(Basett) at follow-up Day 7
453.5
(31.57)
483.5
(46.51)
Corrected QT interval(Fridericia), Day 1,Pre-dose
423.4
(NA)
418.1
(49.03)
Corrected QT interval(Fridericia), Day 3,12 hours
406.3
(20.18)
432.7
(35.92)
Corrected QT interval(Fridericia),follow-up Day 7
419.5
(12.66)
439.6
(36.29)
QTCU on Day 1,Pre-dose
458.3
(8.81)
447.3
(27.65)
QTCU on Day 3,12 hours
440.3
(40.07)
445.4
(28.11)
QTCU at follow-up Day 7
441.6
(17.72)
457.3
(26.12)
RR interval on Day 1,Pre-dose
584.6
(NA)
513.6
(97.25)
RR interval on Day 3,12 hours
638.8
(135.85)
623.2
(76.02)
RR interval at follow-up Day 7
661.7
(203.97)
582.9
(128.96)
4. Primary Outcome
Title Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)
Description Hematology parameters included basophils, eosinophil, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Basophils on Day 1 at Pre-dose
0.020
(NA)
0.000
(0.0000)
Basophils on Day 3 at 12 hours
0.015
(0.0296)
0.011
(0.0277)
Basophils on Follow-up Day 7
0.025
(0.0431)
0.113
(0.1848)
Eosinophils on Day 1 at Pre-dose
0.110
(NA)
0.233
(0.4041)
Eosinophils on Day 3 at 12 hours
0.096
(0.1624)
0.163
(0.2280)
Eosinophils on Follow-up Day 7
0.137
(0.1074)
0.324
(0.4957)
Lymphocytes on Day 1 at Pre-dose
4.81
(4.603)
0.52
(0.266)
Lymphocytes on Day 3 at 12 hours
1.08
(0.948)
0.60
(0.380)
Lymphocytes on Follow-up Day 7
1.61
(1.244)
1.04
(0.663)
Monocytes on Day 1 at Pre-dose
1.760
(1.7112)
0.377
(0.3356)
Monocytes on Day 3 at 12 hours
0.503
(0.4046)
0.571
(0.6336)
Monocytes on Follow-up Day 7
0.669
(0.3986)
0.727
(0.5812)
Total neutrophils on Day 1 at Pre-dose
6.990
(4.5113)
7.807
(9.3471)
Total neutrophils on Day 3 at 12 hours
11.563
(6.0785)
9.931
(6.8583)
Total neutrophils on Follow-up Day 7
16.775
(21.6419)
11.761
(5.5496)
Platelet count on Day 1 at Pre-dose
170.3
(67.26)
236.0
(158.73)
Platelet count on Day 3 at 12 hours
218.9
(120.68)
235.9
(134.43)
Platelet count on Follow-up Day 7
334.1
(169.06)
369.8
(169.70)
White blood cell count on Day 1 at Pre-dose
15.15
(14.289)
10.72
(8.829)
White blood cell count on Day 3 at 12 hours
14.82
(5.927)
11.82
(6.618)
White blood cell count on Follow-up Day 7
14.09
(5.197)
36.56
(84.293)
5. Primary Outcome
Title Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)
Description Hematology parameters included red blood cell count and reticulocyte count. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Red blood cell count on Day 1 at Pre-dose
3.207
(0.7733)
2.678
(0.5117)
Red blood cell count on Day 3 at 12 hours
3.271
(0.5725)
3.076
(0.5001)
Red blood cell count on Follow-up Day 7
3.352
(0.6374)
3.314
(0.7700)
Reticulocyte count on Day 1 at Pre-dose
0.025
(0.0195)
0.044
(NA)
Reticulocyte count on Day 3 at 12 hours
0.832
(2.5186)
3.697
(12.6920)
Reticulocyte count on Follow-up Day 7
1.607
(5.1055)
8.629
(25.6392)
6. Primary Outcome
Title Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)
Description Hematology parameters included hemoglobin and MCHC. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Hemoglobin on Day 1 at Pre-dose
99.5
(24.83)
84.0
(13.09)
Hemoglobin on Day 3 at 12 hours
195.8
(286.77)
180.8
(266.16)
Hemoglobin on Follow-up Day 7
244.7
(401.03)
213.6
(301.50)
MCHC on Day 1 at Pre-dose
331.8
(10.68)
339.5
(19.12)
MCHC on Day 3 at 12 hours
328.4
(14.73)
330.8
(16.82)
MCHC on Follow-up Day 7
327.8
(12.35)
325.4
(6.82)
7. Primary Outcome
Title Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)
Description Hematology parameter included MCV. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
MCV on Day 1 at Pre-dose
77.37
(33.654)
93.87
(0.971)
MCV on Day 3 at 12 hours
91.28
(5.611)
90.69
(5.976)
MCV on Follow-up Day 7
92.53
(7.234)
90.46
(7.063)
8. Primary Outcome
Title Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)
Description Hematology parameter included MCH. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
MCH on Day 1 at Pre-dose
30.30
(4.493)
30.40
(0.361)
MCH on Day 3 at 12 hours
30.02
(2.695)
30.32
(1.955)
MCH on Follow-up Day 7
30.49
(2.545)
30.25
(2.071)
9. Primary Outcome
Title Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)
Description Hematology parameter included hematocrit. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Hematocrit on Day 1 at Pre-dose
0.201
(0.1666)
0.196
(0.1333)
Hematocrit on Day 3 at 12 hours
0.271
(0.1071)
1.519
(5.3867)
Hematocrit on Follow-up Day 7
0.254
(0.1298)
2.270
(7.5504)
10. Primary Outcome
Title Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)
Description Clinical chemistry parameters included calcium, chloride, carbon dioxide, glucose, potassium, sodium, Urea/Blood urea nitrogen. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Calcium on Day 1 at Pre-dose
1.927
(0.0736)
1.894
(0.1070)
Calcium on Day 3 at 12 hours
1.983
(0.1220)
1.982
(0.1296)
Calcium on Follow-up Day 7
2.155
(0.1016)
2.104
(0.1448)
Chloride on Day 1 at Pre-dose
108.8
(5.93)
104.0
(7.18)
Chloride on Day 3 at 12 hours
107.7
(5.12)
106.0
(6.05)
Chloride on Follow-up Day 7
104.4
(3.76)
103.7
(5.01)
Carbon dioxide on Day 1 at Pre-dose
24.40
(5.273)
23.28
(6.685)
Carbon dioxide on Day 3 at 12 hours
26.35
(3.176)
27.83
(6.071)
Carbon dioxide on Follow-up Day 7
27.69
(3.728)
27.39
(3.412)
Glucose on Day 1 at Pre-dose
6.015
(0.7499)
6.159
(1.1230)
Glucose on Day 3 at 12 hours
8.095
(2.1569)
7.411
(1.6158)
Glucose on Follow-up Day 7
6.701
(1.6354)
7.285
(1.5159)
Potassium on Day 1 at Pre-dose
3.88
(0.444)
3.72
(0.164)
Potassium on Day 3 at 12 hours
4.20
(0.511)
3.96
(0.578)
Potassium on Follow-up Day 7
3.83
(0.505)
3.92
(0.435)
Sodium on Day 1 at Pre-dose
141.8
(3.11)
137.6
(3.71)
Sodium on Day 3 at 12 hours
143.1
(4.46)
141.6
(4.03)
Sodium on Follow-up Day 7
141.9
(4.59)
139.7
(4.58)
Urea/Blood urea nitrogen on Day 1 at Pre-dose
6.433
(3.0512)
11.399
(7.4163)
Urea/Blood urea nitrogen on Day 3 at 12 hours
10.410
(6.5542)
9.485
(6.5777)
Urea/Blood urea nitrogen on Follow-up Day 7
11.787
(9.3546)
9.207
(6.5375)
11. Primary Outcome
Title Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)
Description Clinical chemistry parameters included direct bilirubin, total bilirubin, creatinine and uric acid. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Direct bilirubin on Day 1 at Pre-dose
10.663
(7.8146)
13.792
(17.7932)
Direct bilirubin on Day 3 at 12 hours
10.446
(14.2406)
10.428
(22.4573)
Direct bilirubin on Follow-up Day 7
4.140
(3.5564)
2.576
(1.6103)
Total bilirubin on Day 1 at Pre-dose
16.672
(11.1375)
21.926
(20.4768)
Total bilirubin on Day 3 at 12 hours
16.803
(15.8462)
14.119
(24.8465)
Total bilirubin on Follow-up Day 7
12.547
(10.7837)
5.818
(3.0149)
Creatinine on Day 1 at Pre-dose
85.194
(19.9261)
126.228
(71.9085)
Creatinine on Day 3 at 12 hours
108.189
(102.4388)
103.066
(90.6252)
Creatinine on Follow-up Day 7
91.726
(45.2713)
90.516
(71.8052)
Uric acid on Day 1 at Pre-dose
233.432
(67.9909)
181.453
(203.5924)
Uric acid on Day 3 at 12 hours
192.925
(143.7971)
228.144
(134.9558)
Uric acid on Follow-up Day 7
241.766
(72.0137)
225.326
(144.4626)
12. Primary Outcome
Title Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)
Description Clinical chemistry parameters included alkaline phosphatase, asparatate amino transferase, alanine amino transferase, gamma glutamyl transferase. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Alkaline phosphatase on Day 1 at Pre-dose
76.6
(18.57)
94.0
(50.86)
Alkaline phosphatase on Day 3 at 12 hours
130.9
(68.16)
109.2
(63.02)
Alkaline phosphatase on Follow-up Day 7
101.1
(40.15)
117.0
(56.07)
Alanine amino transferase on Day 1 at Pre-dose
101.8
(105.98)
56.8
(42.20)
Alanine amino transferase on Day 3 at 12 hours
73.4
(71.27)
43.6
(50.72)
Alanine amino transferase on Follow-up Day 7
44.9
(42.74)
117.9
(224.94)
Asparatate amino transferase on Day 1 at Pre-dose
96.8
(46.09)
64.6
(37.14)
Asparatate amino transferase on Day 3 at 12 hours
56.2
(34.60)
62.0
(71.54)
Asparatate amino transferase on Follow-up Day 7
35.6
(20.25)
76.5
(106.39)
Gamma glutamyl transferase on Day 1 at Pre-dose
96.0
(22.63)
40.7
(25.89)
Gamma glutamyl transferase on Day 3 at 12 hours
156.5
(149.89)
98.4
(71.85)
Gamma glutamyl transferase on Follow-up Day 7
116.4
(105.36)
143.0
(138.22)
13. Primary Outcome
Title Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)
Description Clinical chemistry parameters included albumin and total protein. Assessments were performed at Pre-dose on Day 1, at 12 hours on Day 3 and at follow-up Day 7.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Albumin on Day 1 at Pre-dose
25.6
(2.19)
18.6
(3.21)
Albumin on Day 3 at 12 hours
25.5
(5.05)
22.3
(4.88)
Albumin on Follow-up Day 7
27.9
(6.62)
25.5
(6.27)
Total protein on Day 1 at Pre-dose
54.60
(5.983)
50.20
(2.775)
Total protein on Day 3 at 12 hours
55.06
(7.122)
52.12
(7.457)
Total protein on Follow-up Day 7
60.86
(8.646)
58.18
(10.323)
14. Primary Outcome
Title Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)
Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part A Population was defined as all participants in Part A who received at least one dose of study medication.
Arm/Group Title Part A
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Measure Participants 5
Any AE
5
100%
Anys SAE
3
60%
15. Primary Outcome
Title Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)
Description An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time Frame Up to Day 7

Outcome Measure Data

Analysis Population Description
All Subjects - Part B Population.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Any AE
14
15
Any SAE
4
3
16. Secondary Outcome
Title Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)
Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part A
Time Frame Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1), 0 hours, 1 hour, 12 hours, 24 hours (Day 2)

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic - Part A Population was defined as participants in the All Subjects - Part A population for whom a pharmacokinetic sample was obtained and analyzed and a result reported and received an active dose of GSK2586881.
Arm/Group Title Part A
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Measure Participants 5
GSK2586881 concentration at Pre-dose on Day 1
NA
(NA)
GSK2586881 concentration at 5 minutes on Day 1
2854.0
(595.47)
GSK2586881 concentration at 10 minutes on Day 1
2692.8
(629.78)
GSK2586881 concentration at 2 hours on Day 1
2047.4
(497.19)
GSK2586881 concentration at 6 hours on Day 1
5460.0
(3213.96)
GSK2586881 concentration at 10 hours on Day 1
10276.6
(2641.49)
GSK2586881 concentration at 12 hours on Day 1
8265.4
(1905.29)
GSK2586881 concentration at 0 hours on Day 2
3621.6
(2654.21)
GSK2586881 concentration at 1 hour on Day 2
17558.6
(4359.04)
GSK2586881 concentration at 12 hours on Day 2
7237.8
(4281.27)
GSK2586881 concentration at 24 hours on Day 2
3517.8
(2433.49)
17. Secondary Outcome
Title Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)
Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3). Data has been presented for GSK2586881 Plasma Pharmacokinetic Concentration versus time data for Part B.
Time Frame Pre-dose, 0.5 Hours, 2 hours, 6 hours, 12 hours (Day 1), 0 hours (Day 2), 0 hours, 0.5 hours, 2 hours, 6 hours, 12 hours, 18 hours and 24 hours (Day 3)

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic - Part B Population was defined as participants in the All Subjects - Part B population for whom a pharmacokinetic sample was obtained and analyzed and a result reported and received an active dose of GSK2586881. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 19
GSK2586881 concentration at Pre-dose on Day 1
NA
(NA)
GSK2586881 concentration at 0.5 hours on Day 1
5489.3
(1727.81)
GSK2586881 concentration at 2 hours on Day 1
4334.0
(1880.42)
GSK2586881 concentration at 6 hours on Day 1
5065.4
(8679.92)
GSK2586881 concentration at 12 hours on Day 1
1815.9
(809.52)
GSK2586881 concentration at 0 hours on Day 2
2115.3
(1164.12)
GSK2586881 concentration at 0 hours on Day 3
2306.6
(1356.75)
GSK2586881 concentration at 0.5 hours on Day 3
6810.4
(3135.66)
GSK2586881 concentration at 2 hours on Day 3
6060.7
(2956.33)
GSK2586881 concentration at 6 hours on Day 3
3808.9
(1953.82)
GSK2586881 concentration at 12 hours on Day 3
2416.6
(1601.08)
GSK2586881 concentration at 18 hours on Day 3
2701.6
(1874.28)
GSK2586881 concentration at 24 hours on Day 3
2254.7
(1233.58)
18. Secondary Outcome
Title Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)
Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.
Time Frame Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours

Outcome Measure Data

Analysis Population Description
Pharmacokinetic - Part A Population.
Arm/Group Title Part A
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Measure Participants 5
Geometric Mean (Standard Error) [liters per hour]
0.384
(0.0886)
19. Secondary Outcome
Title Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)
Description Blood samples for pharmacokinetic analysis of GSK2586881 were collected at Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours and 48 hours. CL was defined as the systemic clearance of parent drug. Clearance was calculated for individual participant and geometric mean of the values from all participants was reported.
Time Frame Pre-dose, 0 hour, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours, 24 hours, 25 hours, 36 hours, 48 hours

Outcome Measure Data

Analysis Population Description
Pharmacokinetic - Part B Population.
Arm/Group Title Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 19
Geometric Mean (Standard Error) [liters per hour]
0.698
(0.0608)
20. Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A)
Description Renin-angiotensin system cascade biomarkers included Ang II and Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.
Time Frame Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).

Outcome Measure Data

Analysis Population Description
All Subjects - Part A Population
Arm/Group Title Part A
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Measure Participants 5
AngII at Pre-dose on Day 1
26.5
AngII at 5 minutes on Day 1
7.7
AngII at 10 minutes on Day 1
6.2
AngII at 2 hours on Day 1
3.9
AngII at 6 hours on Day 1
4.3
AngII at 10 hours on Day 1
2.0
AngII at 12 hours on Day 1
3.3
AngII at 0 hours on Day 2
1.7
AngII at 1 hour on Day 2
4.3
AngII at 12 hours on Day 2
1.8
AngII at 24 hours on Day 2
1.5
Ang1-7 at Pre-dose on Day 1
4.3
Ang1-7 at 5 minutes on Day 1
28.7
Ang1-7 at 10 minutes on Day 1
25.7
Ang1-7 at 2 hours on Day 1
18.7
Ang1-7 at 6 hours on Day 1
22.8
Ang1-7 at 10 hours on Day 1
16.8
Ang1-7 at 12 hours on Day 1
15.1
Ang1-7 at 0 hours on Day 2
9.1
Ang1-7 at 1 hour on Day 2
20.9
Ang1-7 at 12 hours on Day 2
18.8
Ang1-7 at 24 hours on Day 2
5.2
21. Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A)
Description Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-7). Blood samples for biomarker analyses were collected at Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours on Day 1 and 0 hours, 1 hour, 12 hours and 24 hours on Day 2.
Time Frame Pre-dose, 5 minutes, 10 minutes, 2 hours, 6 hours, 10 hours, 12 hours (Day 1) and 0 hours, 1 hour, 12 hours and 24 hours (Day 2).

Outcome Measure Data

Analysis Population Description
All Subjects - Part A Population.
Arm/Group Title Part A
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Measure Participants 5
AngII/ Ang1-7 at Pre-dose on Day 1
6.167
AngII/ Ang1-7 at 5 minutes on Day 1
0.268
AngII/ Ang1-7 at 10 minutes on Day 1
0.241
AngII/ Ang1-7 at 2 hours on Day 1
0.210
AngII/ Ang1-7 at 6 hours on Day 1
0.190
AngII/ Ang1-7 at 10 hours on Day 1
0.118
AngII/ Ang1-7 at 12 hours on Day 1
0.221
AngII/ Ang1-7 at 0 hours on Day 2
0.182
AngII/ Ang1-7 at 1 hour on Day 2
0.206
AngII/ Ang1-7 at 12 hours on Day 2
0.094
AngII/ Ang1-7 at 24 hours on Day 2
0.290
22. Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B)
Description Renin-angiotensin system cascade biomarkers included Ang II, Ang (1-7) and Ang (1-5). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Time Frame 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
AngII at 0.5 hours
14.14
2.44
AngII at 2 hours
12.05
2.80
AngII at 6 hours
11.00
2.89
AngII at 12 hours
10.90
3.33
AngII at 24 hours
8.35
2.41
AngII at 48 hours
8.10
3.74
AngII at 48.5 hours
8.63
2.89
AngII at 50 hours
6.82
2.58
AngII at 54 hours
7.03
2.32
AngII at 60 hours
7.02
2.38
AngII at 66 hours
7.33
1.84
AngII at 72 hours
6.62
1.93
AngII at 96 hours
4.72
1.70
AngII at 120 hours
5.21
2.64
Ang1-5 at 0.5 hours
2.17
8.58
Ang1-5 at 2 hours
2.18
7.50
Ang1-5 at 6 hours
2.34
8.38
Ang1-5 at 12 hours
2.78
5.07
Ang1-5 at 24 hours
2.38
3.57
Ang1-5 at 48 hours
2.39
4.59
Ang1-5 at 48.5 hours
2.30
5.26
Ang1-5 at 50 hours
2.53
4.91
Ang1-5 at 54 hours
2.52
3.21
Ang1-5 at 60 hours
2.26
2.78
Ang1-5 at 66 hours
2.19
2.71
Ang1-5 at 72 hours
1.72
2.50
Ang1-5 at 96 hours
2.23
1.28
Ang1-5 at 120 hours
2.19
1.38
Ang1-7 at 0.5 hours
3.12
13.15
Ang1-7 at 2 hours
3.29
12.05
Ang1-7 at 6 hours
2.92
15.33
Ang1-7 at 12 hours
3.03
6.82
Ang1-7 at 24 hours
2.87
6.25
Ang1-7 at 48 hours
3.58
5.71
Ang1-7 at 48.5 hours
2.77
5.54
Ang1-7 at 50 hours
3.20
6.13
Ang1-7 at 54 hours
3.16
5.78
Ang1-7 at 60 hours
3.57
4.74
Ang1-7 at 66 hours
3.40
3.97
Ang1-7 at 72 hours
2.66
4.70
Ang1-7 at 96 hours
1.77
2.43
Ang1-7 at 120 hours
2.38
3.21
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.083 to 0.359
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9999
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.111 to 0.492
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9997
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.121 to 0.568
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9997
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.136 to 0.660
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9991
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.133 to 0.632
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9631
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.213 to 1.081
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9941
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.33
Confidence Interval () 95%
0.157 to 0.789
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9875
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.179 to 0.891
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9956
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.151 to 0.759
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9964
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.157 to 0.747
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9999
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.114 to 0.532
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9991
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.130 to 0.647
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9852
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.36
Confidence Interval (2-Sided) 0.9852%
0.137 to 0.906
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9719
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.230 to 1.014
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.98
Confidence Interval (2-Sided) 95%
2.263 to 6.919
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.46
Confidence Interval (2-Sided) 95%
1.976 to 6.052
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.59
Confidence Interval (2-Sided) 95%
2.060 to 6.345
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9806
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.82
Confidence Interval (2-Sided) 95%
1.031 to 3.170
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.9129
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
0.828 to 2.636
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.9891
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.92
Confidence Interval (2-Sided) 95%
1.098 to 3.349
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9983
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 2.29
Confidence Interval (2-Sided) 95%
1.316 to 3.974
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9900
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.94
Confidence Interval (2-Sided) 95%
1.112 to 3.359
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7996
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.729 to 2.163
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7778
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.718 to 2.087
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7730
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.705 to 2.113
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8951
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
0.814 to 2.604
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9324
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.276 to 1.183
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8982
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.351 to 1.257
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9998
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 4.22
Confidence Interval (2-Sided) 95%
1.910 to 8.905
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9993
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 3.67
Confidence Interval (2-Sided) 95%
1.689 to 7.970
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 5.26
Confidence Interval (2-Sided) 95%
2.392 to 11.754
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9713
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
0.972 to 5.136
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9649
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 2.19
Confidence Interval (2-Sided) 95%
0.940 to 4.975
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8749
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
0.711 to 3.473
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9566
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.99
Confidence Interval (2-Sided) 95%
0.899 to 4.342
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9549
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
0.862 to 4.173
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9275
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
0.816 to 4.005
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.7483
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.584 to 3.007
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6480
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.516 to 2.675
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9038
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.76
Confidence Interval (2-Sided) 95%
0.741 to 4.170
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7339
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.490 to 3.915
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7714
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.651 to 3.321
Parameter Dispersion Type:
Value:
Estimation Comments
23. Secondary Outcome
Title Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/Ang (1-5) and Ang II/Ang (1-7) Upto Day 5(Part B)
Description Renin-angiotensin system cascade biomarkers included Ang II/Ang (1-5) and Ang II/Ang (1-7) and). Blood samples for biomarker analyses were collected 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Time Frame 0.5 hours, 2 hours, 6 hours, 12 hours, 24 hours, 48 hours, 48.5 hours, 50 hours, 54 hours, 60 hours, 66 hours, 72 hours, 96 hours and 120 hours upto Day 5.

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Ang II/Ang1-5 at 0.5 hours
4.35
0.29
Ang II/Ang1-5 at 2 hours
3.82
0.38
Ang II/Ang1-5 at 6 hours
3.20
0.36
Ang II/Ang1-5 at 12 hours
2.90
0.72
Ang II/Ang1-5 at 24 hours
2.35
0.68
Ang II/Ang1-5 at 48 hours
2.68
0.85
Ang II/Ang1-5 at 48.5 hours
2.90
0.56
Ang II/Ang1-5 at 50 hours
2.11
0.53
Ang II/Ang1-5 at 54 hours
2.21
0.68
Ang II/Ang1-5 at 60 hours
2.52
0.86
Ang II/Ang1-5 at 66 hours
2.90
0.64
Ang II/Ang1-5 at 72 hours
2.91
0.76
Ang II/Ang1-5 at 96 hours
1.72
1.41
Ang II/Ang1-5 at 120 hours
1.93
1.53
Ang II/Ang1-7 at 0.5 hours
3.10
0.19
Ang II/Ang1-7 at 2 hours
2.52
0.24
Ang II/Ang1-7 at 6 hours
2.63
0.20
Ang II/Ang1-7 at 12 hours
2.50
0.49
Ang II/Ang1-7 at 24 hours
2.11
0.37
Ang II/Ang1-7 at 48 hours
1.61
0.65
Ang II/Ang1-7 at 48.5 hours
2.18
0.51
Ang II/Ang1-7 at 50 hours
1.51
0.42
Row 23Ang II/Ang1-7 at 54 hours
1.64
0.40
Ang II/Ang1-7 at 60 hours
1.55
0.48
Ang II/Ang1-7 at 66 hours
1.81
0.45
Ang II/Ang1-7 at 72 hours
1.75
0.42
Ang II/Ang1-7 at 96 hours
2.02
0.69
Ang II/Ang1-7 at 120 hours
1.66
0.64
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.032 to 0.140
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.048 to 0.209
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.054 to 0.243
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9996
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.113 to 0.547
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9991
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.130 to 0.634
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9979
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.149 to 0.682
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.19
Confidence Interval () 95%
0.091 to 0.417
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9998
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.119 to 0.539
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9985
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.141 to 0.666
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9977
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.162 to 0.730
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9999
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.105 to 0.468
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9996
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.119 to 0.570
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6621
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.319 to 2.136
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7085
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.324 to 1.847
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
0.028 to 0.140
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.043 to 0.216
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 1.0000
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0.034 to 0.177
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9998
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.086 to 0.453
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9999
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.075 to 0.400
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9863
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.173 to 0.901
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9998
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.103 to 0.529
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9992
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.119 to 0.626
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9995
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.102 to 0.561
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9964
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.131 to 0.729
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9995
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.107 to 0.584
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9993
Comments
Method Ratio of Active/Placebo
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.098 to 0.578
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9781
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.119 to 0.969
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9375
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.154 to 1.341
Parameter Dispersion Type:
Value:
Estimation Comments
24. Secondary Outcome
Title Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B)
Description Measures of oxygenation included PEEP the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration, peak ventilator pressure highest level of pressure applied to the lungs during inhalation and plateau ventilatory pressure the pressure applied to small airways and alveoli measured during an inspiratory pause on the ventilator. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.
Time Frame 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
PEEP at 0.5 hours
10.3
9.6
PEEP at 1 hour
9.9
9.6
PEEP at 2 hours
9.9
9.7
PEEP at 4 hours
9.7
9.6
PEEP at 6 hours
9.6
9.5
PEEP at 8 hours
9.7
9.6
PEEP at 12 hours
9.8
9.5
PEEP at 18 hours
10.1
9.6
PEEP at 24 hours
9.7
9.3
PEEP at 24.5 hours
9.7
9.3
PEEP at 25 hours
9.7
8.6
PEEP at 26 hours
9.4
9.3
PEEP at 28 hours
9.1
9.4
PEEP at 30 hours
9.5
9.3
PEEP at 32 hours
9.1
9.2
PEEP at 36 hours
9.3
9.0
PEEP at 42 hours
9.6
8.9
PEEP at 48 hours
9.6
8.8
PEEP at 48.5 hours
9.6
8.8
PEEP at 49 hours
9.6
8.6
PEEP at 50 hours
9.6
8.7
PEEP at 52 hours
9.6
8.8
PEEP at 54 hours
9.4
8.7
PEEP at 56 hours
9.2
8.7
PEEP at 60 hours
8.9
8.2
PEEP at 66 hours
9.4
9.1
PEEP at 72 hours
9.6
8.8
PEEP at 168 hours
6.9
7.5
Peak ventilatory pressure at 0.5 hours
29.3
29.7
Peak ventilatory pressure at 1 hour
28.3
30.4
Peak ventilatory pressure at 2 hours
27.7
29.7
Peak ventilatory pressure at 4 hours
28.4
28.8
Peak ventilatory pressure at 6 hours
28.1
29.4
Peak ventilatory pressure at 8 hours
28.2
29.3
Peak ventilatory pressure at 12 hours
28.5
29.7
Peak ventilatory pressure at 18 hours
29.5
28.9
Peak ventilatory pressure at 24 hours
28.8
28.3
Peak ventilatory pressure at 24.5 hours
29.1
28.2
Peak ventilatory pressure at 25 hours
29.4
27.2
Peak ventilatory pressure at 26 hours
27.6
27.4
Peak ventilatory pressure at 28 hours
29.3
26.9
Peak ventilatory pressure at 30 hours
29.5
28.6
Peak ventilatory pressure at 32 hours
30.7
28.1
Peak ventilatory pressure at 36 hours
30.7
27.0
Peak ventilatory pressure at 42 hours
28.2
27.6
Peak ventilatory pressure at 48 hours
25.7
26.7
Peak ventilatory pressure at 48.5 hours
26.0
28.1
Peak ventilatory pressure at 49 hours
26.4
28.1
Peak ventilatory pressure at 50 hours
24.2
27.3
Peak ventilatory pressure at 52 hours
26.6
26.7
Peak ventilatory pressure at 54 hours
25.3
27.3
Peak ventilatory pressure at 56 hours
25.6
27.9
Peak ventilatory pressure at 60 hours
24.1
26.8
Peak ventilatory pressure at 66 hours
24.3
25.9
Peak ventilatory pressure at 72 hours
22.9
29.3
Peak ventilatory pressure at 168 hours
19.9
25.2
Plateau ventilatory pressure at 0.5 hours
24.2
25.9
Plateau ventilatory pressure at 1 hour
24.8
24.7
Plateau ventilatory pressure at 2 hours
23.9
24.8
Plateau ventilatory pressure at 4 hours
24.3
24.9
Plateau ventilatory pressure at 6 hours
24.8
25.2
Plateau ventilatory pressure at 8 hours
25.9
21.9
Plateau ventilatory pressure at 12 hours
24.1
24.0
Plateau ventilatory pressure at 18 hours
25.3
21.5
Plateau ventilatory pressure at 24 hours
24.1
24.2
Plateau ventilatory pressure at 24.5 hours
23.8
23.2
Plateau ventilatory pressure at 25 hours
24.4
22.2
Plateau ventilatory pressure at 26 hours
23.3
23.2
Plateau ventilatory pressure at 28 hours
23.1
23.4
Plateau ventilatory pressure at 30 hours
23.3
23.6
Plateau ventilatory pressure at 32 hours
23.2
23.2
Plateau ventilatory pressure at 36 hours
23.4
23.7
Plateau ventilatory pressure at 42 hours
24.8
23.3
Plateau ventilatory pressure at 48 hours
23.6
23.1
Plateau ventilatory pressure at 48.5 hours
23.1
25.2
Plateau ventilatory pressure at 49 hours
22.8
24.6
Plateau ventilatory pressure at 50 hours
22.3
25.2
Plateau ventilatory pressure at 52 hours
23.9
25.4
Plateau ventilatory pressure at 54 hours
23.1
23.1
Plateau ventilatory pressure at 56 hours
23.2
22.4
Plateau ventilatory pressure at 60 hours
22.5
23.4
Plateau ventilatory pressure at 66 hours
24.5
23.6
Plateau ventilatory pressure at 72 hours
21.7
25.3
Plateau ventilatory pressure at 168 hours
15.1
17.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2598
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.752 to 1.215
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hour
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3949
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.783 to 1.273
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4175
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.791 to 1.294
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4420
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.806 to 1.292
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4432
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.811 to 1.262
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4578
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.818 to 1.229
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3365
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.790 to 1.167
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3339
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.770 to 1.163
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3608
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.786 to 1.166
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3584
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.788 to 1.168
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1219
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.725 to 1.073
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4662
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.814 to 1.210
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5748
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.828 to 1.247
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4104
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.786 to 1.204
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5114
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.817 to 1.246
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4213
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.783 to 1.200
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2663
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.731 to 1.132
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2373
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.720 to 1.142
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2575
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.721 to 1.149
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2173
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.708 to 1.127
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2406
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.717 to 1.143
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2471
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.721 to 1.151
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2585
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.727 to 1.157
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3101
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.737 to 1.170
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2476
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.727 to 1.160
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3887
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.767 to 1.222
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.2294
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.749 to 1.146
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8522
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.916 to 1.234
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5885
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.890 to 1.164
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hour
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8558
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.940 to 1.230
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hour
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8374
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.932 to 1.224
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5886
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.887 to 1.152
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7532
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.918 to 1.180
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7108
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.906 to 1.179
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7445
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.918 to 1.190
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3759
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.863 to 1.115
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3980
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.859 to 1.118
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3231
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.849 to 1.103
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1245
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.812 to 1.056
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4631
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.870 to 1.134
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1026
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.801 to 1.047
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3152
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.850 to 1.101
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0762
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.803 to 1.035
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0274
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.88
Confidence Interval () 95%
0.763 to 1.003
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3594
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.853 to 1.112
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7027
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.906 to 1.197
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8661
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.941 to 1.246
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8084
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.924 to 1.228
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 49
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9504
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.976 to 1.300
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 50
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5300
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.871 to 1.164
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 51
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8595
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.942 to 1.243
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 52
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8802
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.943 to 1.261
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 53
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9232
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.958 to 1.278
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 54
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7911
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.902 to 1.256
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 55
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9946
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
1.059 to 1.514
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 56
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9830
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
1.019 to 1.444
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 57
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8024
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.910 to 1.261
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 58
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hour
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4806
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.843 to 1.166
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 59
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6658
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.869 to 1.223
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 60
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6131
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.856 to 1.212
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 61
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5795
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.856 to 1.197
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 62
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0209
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.716 to 0.993
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 63
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4823
Comments
Method Mixed Models Analysis
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.830 to 1.187
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 64
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0406
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter 0.0406
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.703 to 1.021
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 65
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5186
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.844 to 1.169
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 66
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3870
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.824 to 1.132
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 67
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1281
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.770 to 1.065
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 68
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4754
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.837 to 1.181
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 69
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5627
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.856 to 1.217
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 70
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5552
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.848 to 1.220
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 71
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5030
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.843 to 1.201
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 72
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5558
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.840 to 1.218
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 73
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2709
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.769 to 1.135
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 74
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4143
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.795 to 1.208
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 75
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7886
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.891 to 1.348
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 76
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7607
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.885 to 1.353
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 77
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8677
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.922 to 1.400
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 78
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7012
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.847 to 1.302
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 79
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5156
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.805 to 1.230
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 80
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3524
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.783 to 1.178
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 81
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6380
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.845 to 1.292
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 82
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4003
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.743 to 1.241
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 83
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8817
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.907 to 1.502
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 84
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8145
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.804 to 1.505
Parameter Dispersion Type:
Value:
Estimation Comments
25. Secondary Outcome
Title Measure of Oxygenation Including Fraction of Inspired Oxygen/ Partial Pressure of Oxygen in Arterial Blood (PaO2/FiO2) Ratio Via Pulse Oximetry Upto Day 7 (Part B)
Description Measure of oxygenation included PaO2/FiO2 ratio defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen by pulse oximeter a device that measured the oxygen saturation of arterial blood in a participant by utilizing a sensor attached typically to a finger, toe, or ear to determine the percentage of oxyhemoglobin in blood pulsating through a network of capillaries. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.
Time Frame 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
PaO2/FiO2 at 0.5 hours
166.2
173.7
PaO2/FiO2 at 1 hour
178.1
160.2
PaO2/FiO2 at 2 hours
181.5
162.3
PaO2/FiO2 at 4 hours
182.8
155.1
PaO2/FiO2 at 6 hours
173.2
156.7
PaO2/FiO2 at 8 hours
160.9
170.6
PaO2/FiO2 at 12 hours
173.7
179.6
PaO2/FiO2 at 18 hours
180.5
176.8
PaO2/FiO2 at 24 hours
183.5
167.3
PaO2/FiO2 at 24.5 hours
189.3
175.8
PaO2/FiO2 at 25 hours
179.6
167.1
PaO2/FiO2 at 26 hours
182.9
183.2
PaO2/FiO2 at 28 hours
191.1
167.9
PaO2/FiO2 at 30 hours
169.5
169.3
PaO2/FiO2 at 32 hours
174.2
155.3
PaO2/FiO2 at 36 hours
200.5
159.5
PaO2/FiO2 at 42 hours
172.7
171.0
PaO2/FiO2 at 48 hours
169.9
178.2
PaO2/FiO2 at 48.5 hours
195.8
175.5
PaO2/FiO2 at 49 hours
166.5
175.1
PaO2/FiO2 at 50 hours
168.3
167.5
PaO2/FiO2 at 52 hours
183.9
168.4
PaO2/FiO2 at 54 hours
191.6
172.1
PaO2/FiO2 at 56 hours
181.6
173.9
PaO2/FiO2 at 60 hours
170.8
162.4
PaO2/FiO2 at 66 hours
154.6
162.6
PaO2/FiO2 at 72 hours
150.4
153.3
PaO2/FiO2 at 168 hours
198.9
168.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6468
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.765 to 1.321
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hour
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1965
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.658 to 1.136
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1681
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.694 to 1.129
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0877
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.669 to 1.075
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2011
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.715 to 1.159
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6855
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.842 to 1.345
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6093
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.800 to 1.325
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4350
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.765 to 1.253
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2232
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.722 to 1.195
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2716
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.733 to 1.200
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2866
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.726 to 1.190
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5033
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.780 to 1.270
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1493
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.684 to 1.120
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4947
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.759 to 1.301
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1951
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.678 to 1.161
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0512
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.612 to 1.050
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4700
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.775 to 1.279
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6340
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.811 to 1.368
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2129
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.689 to 1.183
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6418
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.798 to 1.411
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4797
Comments
Method Ratio of Active/Placebo
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.754 to 1.315
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2659
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.703 to 1.199
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2102
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.687 to 1.159
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3623
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.740 to 1.240
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3499
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.730 to 1.225
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6494
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.787 to 1.377
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5567
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.766 to 1.358
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1095
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.615 to 1.073
Parameter Dispersion Type:
Value:
Estimation Comments
26. Secondary Outcome
Title Measure of Oxygenation Index Upto Day 7 (Part B)
Description Oxygenation index was defined as calculation used in intensive care medicine to measure the fraction of inspired oxygen (FiO2) and its usage within the body and was computed using the equation Oxygenation Index= FiO2 x Mean Airway Pressure/Pao2. Assessments were performed at 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7. Data has been presented for median along with the 95% credible interval.
Time Frame 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 24.5, 25, 26, 28, 30, 32, 36, 42, 48, 48.5, 49, 50, 52, 54, 56, 60, 66, 72 and 168 hours upto Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Oxygenation index at 0.5 hours
10.0
10.6
Oxygenation index at 1 hour
9.0
12.2
Oxygenation index at 2 hours
9.9
11.0
Oxygenation index at 4 hours
9.3
11.6
Oxygenation index at 6 hours
10.2
12.3
Oxygenation index at 8 hours
10.4
12.4
Oxygenation index at 12 hours
9.3
11.0
Oxygenation index at 18 hours
8.7
10.8
Oxygenation index at 24 hours
10.6
10.6
Oxygenation index at 24.5 hours
9.0
9.6
Oxygenation index at 25 hours
8.9
10.5
Oxygenation index at 26 hours
9.2
8.3
Oxygenation index at 28 hours
9.0
9.4
Oxygenation index at 30 hours
9.8
9.6
Oxygenation index at 32 hours
9.7
10.4
Oxygenation index at 36 hours
8.7
10.1
Oxygenation index at 42 hours
9.4
10.2
Oxygenation index at 48 hours
10.2
8.8
Oxygenation index at 48.5 hours
9.2
8.4
Oxygenation index at 49 hours
10.8
8.9
Oxygenation index at 50 hours
10.4
9.2
Oxygenation index at 52 hours
9.8
9.4
Oxygenation index at 54 hours
9.4
9.7
Oxygenation index at 56 hours
9.3
8.5
Oxygenation index at 60 hours
8.9
9.9
Oxygenation index at 66 hours
10.5
8.2
Oxygenation index at 72 hours
10.5
9.7
Oxygenation index at 168 hours
5.8
6.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6098
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.721 to 1.644
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hour
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9441
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
0.931 to 2.068
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7173
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.749 to 1.621
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8292
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.810 to 1.949
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8008
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.775 to 1.832
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7905
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.776 to 1.799
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7566
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.737 to 1.958
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8349
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.812 to 2.050
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4739
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.713 to 1.527
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6291
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.763 to 1.647
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8032
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.830 to 1.814
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3250
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.626 to 1.416
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5828
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.687 to 1.630
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4546
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.661 to 1.512
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6158
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.719 to 1.639
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7748
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.752 to 1.770
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6565
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.686 to 1.714
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2773
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.566 to 1.380
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3606
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.610 to 1.467
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2211
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.555 to 1.317
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2860
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.587 to 1.348
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4079
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.609 to 1.510
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5284
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.614 to 1.663
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3586
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.568 to 1.458
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6768
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.672 to 1.853
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1574
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.488 to 1.390
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3900
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.521 to 1.584
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5915
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.748 to 1.516
Parameter Dispersion Type:
Value:
Estimation Comments
27. Secondary Outcome
Title Number of Participants With Acute Kidney Injury as Defined by Day 1 to Day 3 Change in Risk, Injury, Failure, Loss of Kidney Function, and End-stage Kidney Disease (RIFLE) Criteria Upto Day 3 (Part B)
Description The RIFLE score is made up of the glomerular filtration rate criteria (GFRC) and urine output criteria (UOC) and is defined as Risk (Serum Creatinine x 1.5 or GFR decrease > 25%-GFRC and < 0.5 milliliter/kilograms/hour [ml/kg/hour] x 6 hours-UOC), Injury (Serum Creatinine x 2 or GFR decrease > 50%-GFRC and < 0.5 ml/kg/hour x 12 hours), Failure (Serum Creatinine x 3, or GFR decrease > 75% [F=Failure] or Serum Creatinine >=4 milligrams/deciliter [mg/dl] with an acute rise > 0.5 mg/dl [Fc=Failure acute on chronic] and < 0.3 ml/kg/hour x 24 hours, or anuria x 12 hours [Fo=Failure oligouria]). Due to the duration of this study it was not possible to be calculate the designated RIFLE class Loss and RIFLE class End-stage kidney disease. Data has been presented for rifle score total, rifle score GFR and rifle score urine. Abbreviations NAKI= No acute kidney injury, R=risk, I=injury, MISS= Unable to derive score.
Time Frame Upto Day 3

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Rifle score total, MISS
15
300%
14
70%
Rifle score total, NAKI to NAKI
3
60%
1
5%
Rifle score total, NAKI to R
1
20%
0
0%
Rifle score total, R to NAKI
1
20%
1
5%
Rifle score total, I to NAKI
0
0%
1
5%
Rifle score total, I to I
0
0%
1
5%
Rifle score total, Fo to I
0
0%
1
5%
Rifle score GFR, MISS
15
300%
14
70%
Rifle score GFR, NAKI to NAKI
5
100%
2
10%
Rifle score GFR, R to I
0
0%
1
5%
Rifle score GFR, I to NAKI
0
0%
1
5%
Rifle score GFR, I to I
0
0%
1
5%
Rifle score urine, NAKI to NAKI
10
200%
11
55%
Rifle score urine, NAKI to Fo
0
0%
1
5%
Rifle score urine, NAKI to R
2
40%
0
0%
Rifle score urine, NAKI to I
2
40%
0
0%
Rifle score urine, R to NAKI
1
20%
2
10%
Rifle score urine, I to NAKI
3
60%
2
10%
Rifle score urine, I to R
0
0%
1
5%
Rifle score urine, Fo to NAKI
1
20%
0
0%
Rifle score urine, Fo to R
0
0%
1
5%
Rifle score urine, Fo to Fo
1
20%
1
5%
28. Secondary Outcome
Title Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B)
Description The SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). The score ranges from 0-24. 0 (normal) to 4 (high degree of dysfunction) is given for each organ system, with a higher score indicating greater severity. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.
Time Frame Day 4 and Day 7

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Total SOFA Score at Day 4
7.4
8.0
Total SOFA Score at Day 7
5.4
6.8
29. Secondary Outcome
Title Biomarker Analysis for Serum Inflammatory Biomarkers, Markers of Neutrophil Activation, Markers of Lung Epithelial Cell Injury, Renin Levels and Aldosterone Levels Upto Day 5 (Part B)
Description Serum inflammatory biomarkers included CXCL-8 [IL-8], IL-6, markers of neutrophil activation included (e.g. myeloperoxidase [MPO]), markers of lung epithelial cell injury included receptor for advanced glycation end-products [RAGE], Angiopoietin 2, along with rennin, aldosterone levels. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Time Frame 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
CXCL-8 (IL-8) at 12 hours
18.7
16.6
CXCL-8 (IL-8) at 24 hours
17.5
16.8
CXCL-8 (IL-8) at 48 hours
22.3
14.6
CXCL-8 (IL-8) at 72 hours
14.5
14.1
CXCL-8 (IL-8) at 120 hours
10.0
11.8
IL-6 at 12 hours
316.2
313.9
IL-6 at 24 hours
317.9
231.6
IL-6 at 48 hours
310.5
159.8
IL-6 at 72 hours
249.9
180.7
IL-6 at 120 hours
142.2
66.2
RAGE at 12 hours
3746
3461
RAGE at 24 hours
3059
3054
RAGE at 48 hours
2531
2480
RAGE at 72 hours
1936
1755
RAGE at 120 hours
1252
1292
MPO at 12 hours
60161.0
65791.2
MPO at 24 hours
55141.5
69059.0
MPO at 48 hours
58717.0
73790.1
MPO at 72 hours
42521.0
60700.1
MPO at 120 hours
32313.1
47835.2
Angiopoietin-2 at 12 hours
10816.2
8981.1
Angiopoietin-2 at 24 hours
9127.2
8973.9
Angiopoietin-2 at 48 hours
9546.3
9043.3
Angiopoietin-2 at 72 hours
8859.1
7773.7
Angiopoietin-2 at 120 hours
7047.7
6604.4
Renin at 72 hours
19.95
13.60
Aldosterone at 72 hours
36.8
19.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.06828
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.528 to 1.501
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5674
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.570 to 1.609
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8855
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.321 to 1.316
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5358
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.531 to 1.760
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6990
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.622 to 2.155
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5130
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.549 to 1.721
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7696
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.300 to 1.731
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9254
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.203 to 1.289
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7088
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.216 to 2.419
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8787
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.112 to 1.690
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7338
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.714 to 1.197
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4955
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.703 to 1.415
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5264
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.541 to 1.788
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6183
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.454 to 1.742
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5291
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.483 to 2.118
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7400
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.828 to 1.448
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9375
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.937 to 1.683
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9118
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.896 to 1.771
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9217
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
0.866 to 2.382
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8676
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.48
Confidence Interval (2-Sided) 95%
0.730 to 3.064
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8835
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.609 to 1.135
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5446
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.723 to 1.330
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6267
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.679 to 1.333
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7668
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.612 to 1.260
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6100
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.588 to 1.509
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Renin, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.8159
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.291 to 1.623
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments Aldosterone, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7988
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.106 to 2.657
Parameter Dispersion Type:
Value:
Estimation Comments
30. Secondary Outcome
Title Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B)
Description Serum inflammatory biomarker included CRP. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Time Frame 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
CRP at 12 hours
12.99
14.58
CRP at 24 hours
11.26
14.68
CRP at 48 hours
11.19
13.71
CRP at 72 hours
9.96
8.96
CRP at 120 hours
6.81
8.78
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6536
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.626 to 2.024
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9066
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.876 to 1.955
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7859
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.723 to 2.066
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6058
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.413 to 1.963
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6921
Comments
Method Ratio of Active/Placebo
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.456 to 3.632
Parameter Dispersion Type:
Value:
Estimation Comments
31. Secondary Outcome
Title Biomarker Analysis for Markers of Lung Epithelial Cell Injury Clara Cell Protein 16 [CCP16]) and Surfactant Protein D [SP-D] Upto Day 5 (Part B)
Description Markers of lung epithelial cell injury included CCP16 and SP-D. Blood samples for biomarker analyses were collected 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5. Data has been presented for median along with the 95% credible interval.
Time Frame 12 hours, 24 hours, 48 hours, 72 hours and 120 hours upto Day 5

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
CCP-16 at 12 hours
9.24
8.45
CCP-16 at 24 hours
9.18
9.25
CCP-16 at 48 hours
9.91
11.04
CCP-16 at 72 hours
9.04
8.94
CCP-16 at 120 hours
8.94
7.22
SP-D at 12 hours
304.71
384.58
SP-D at 24 hours
348.51
442.35
SP-D at 48 hours
307.00
494.70
SP-D at 72 hours
281.79
465.15
SP-D at 120 hours
229.94
350.31
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7934
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.737 to 1.140
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5205
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.782 to 1.317
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.6682
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.673 to 1.865
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5304
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.744 to 1.315
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9078
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.582 to 1.112
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9907
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
1.042 to 1.526
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9973
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
1.005 to 1.606
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9954
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
1.130 to 2.331
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9830
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
1.045 to 2.588
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B (Placebo BID), Part B (GSK2586881 BID)
Comments SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hours
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9312
Comments
Method Bayesian repeated measures model
Comments
Method of Estimation Estimation Parameter Ratio of Active/Placebo
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
0.867 to 2.737
Parameter Dispersion Type:
Value:
Estimation Comments
32. Secondary Outcome
Title Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A)
Description Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.
Time Frame Follow-up (Day 14) and follow-up (Day 28)

Outcome Measure Data

Analysis Population Description
The All Subjects - Part A Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part A
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 milligrams per kg [mg/kg], 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days.
Measure Participants 5
Day 14, Screening positive Confirmed negative
1
20%
Day 14, Screening positive and Confirmed positive
0
0%
Day 14, Screening negative
1
20%
Day 28, Screening positive Confirmed negative
0
0%
Day 28, Screening positive and Confirmed positive
NA
NaN
Row 6, Screening negative
1
20%
33. Secondary Outcome
Title Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B)
Description Blood samples for immunogenicity analysis were collected at follow-up (Day 14) and follow-up (Day 28). Antibodies to GSK2586881 were measured using a validated electrochemiluminescence bridging assay. All pre-dose and post-dose samples were first tested for Anti-ACE2 binding antibodies by screening and confirmation assay steps. The post-dose samples tested positive for anti-ACE2 binding antibodies were further characterized for anti-ACE2 neutralizing antibodies. Testing was conducted using a tiered approach; samples were first tested in a screening assay, only samples found positive in this assay were tested in the confirmation assay.
Time Frame Follow-up (Day 14 )and follow-up (Day 28)

Outcome Measure Data

Analysis Population Description
The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
Measure Participants 20 19
Day 14, Screening positive Confirmed negative
1
20%
0
0%
Day 14, Screening positive and Confirmed positive
0
0%
NA
NaN
Day 14, Screening negative
8
160%
13
65%
Day 28, Screening positive Confirmed negative
0
0%
0
0%
Day 28, Screening positive and Confirmed positive
NA
NaN
NA
NaN
Day 28, Screening negative
10
200%
11
55%

Adverse Events

Time Frame Upto follow-up Day 7.
Adverse Event Reporting Description The All subjects population was used for analysis.
Arm/Group Title Part A Part B (Placebo BID) Part B (GSK2586881 BID)
Arm/Group Description Eligible participants received multiple single intravenous escalating doses of GSK2586881 (0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg) as a slow infusion over 3-5 minutes over 2 days. Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days.
All Cause Mortality
Part A Part B (Placebo BID) Part B (GSK2586881 BID)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/5 (60%) 2/20 (10%) 1/19 (5.3%)
Serious Adverse Events
Part A Part B (Placebo BID) Part B (GSK2586881 BID)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/5 (60%) 4/20 (20%) 3/19 (15.8%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation 1/5 (20%) 0/20 (0%) 0/19 (0%)
Cardiac disorders
Cardiac arrest 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage 1/5 (20%) 0/20 (0%) 0/19 (0%)
General disorders
Multi-organ failure 1/5 (20%) 1/20 (5%) 0/19 (0%)
Immune system disorders
Graft versus host disease 1/5 (20%) 0/20 (0%) 0/19 (0%)
Infections and infestations
Influenza 1/5 (20%) 0/20 (0%) 0/19 (0%)
Sepsis 1/5 (20%) 0/20 (0%) 0/19 (0%)
Empyema 0/5 (0%) 1/20 (5%) 0/19 (0%)
Pneumonia 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Septic shock 0/5 (0%) 1/20 (5%) 0/19 (0%)
Injury, poisoning and procedural complications
Bronchial anastomosis complication 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Investigations
Hepatic enzyme increased 0/5 (0%) 1/20 (5%) 0/19 (0%)
Nervous system disorders
Subarachnoid haemorrhage 1/5 (20%) 0/20 (0%) 0/19 (0%)
Renal and urinary disorders
Renal failure acute 1/5 (20%) 0/20 (0%) 0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome 1/5 (20%) 0/20 (0%) 0/19 (0%)
Respiratory failure 1/5 (20%) 1/20 (5%) 1/19 (5.3%)
Pleural effusion 0/5 (0%) 1/20 (5%) 0/19 (0%)
Other (Not Including Serious) Adverse Events
Part A Part B (Placebo BID) Part B (GSK2586881 BID)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/5 (100%) 14/20 (70%) 15/19 (78.9%)
Blood and lymphatic system disorders
Anaemia 2/5 (40%) 6/20 (30%) 3/19 (15.8%)
Thrombocytopenia 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Thrombocytosis 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Leukocytosis 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Cardiac disorders
Atrial fibrillation 3/5 (60%) 0/20 (0%) 1/19 (5.3%)
Cardiac failure 1/5 (20%) 0/20 (0%) 0/19 (0%)
Ventricular tachycardia 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Arrhythmia 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Bradycardia 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Cyanosis 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Pericardial effusion 0/5 (0%) 1/20 (5%) 0/19 (0%)
Tachyarrhythmia 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Ear and labyrinth disorders
Ear pain 1/5 (20%) 1/20 (5%) 0/19 (0%)
Eye disorders
Eye haemorrhage 0/5 (0%) 1/20 (5%) 0/19 (0%)
Gastrointestinal disorders
Diarrhoea 2/5 (40%) 3/20 (15%) 3/19 (15.8%)
Abdominal pain 1/5 (20%) 1/20 (5%) 0/19 (0%)
Constipation 1/5 (20%) 3/20 (15%) 2/19 (10.5%)
Nausea 1/5 (20%) 1/20 (5%) 2/19 (10.5%)
Vomiting 1/5 (20%) 0/20 (0%) 1/19 (5.3%)
Dysphagia 0/5 (0%) 1/20 (5%) 5/19 (26.3%)
Abdominal distension 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Ascites 0/5 (0%) 1/20 (5%) 0/19 (0%)
Gastrointestinal haemorrhage 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Toothache 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
General disorders
Generalised oedema 1/5 (20%) 3/20 (15%) 3/19 (15.8%)
Injection site haemorrhage 1/5 (20%) 0/20 (0%) 0/19 (0%)
Pyrexia 1/5 (20%) 0/20 (0%) 0/19 (0%)
Pain 0/5 (0%) 1/20 (5%) 3/19 (15.8%)
Asthenia 0/5 (0%) 1/20 (5%) 2/19 (10.5%)
Peripheral swelling 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Catheter site haemorrhage 0/5 (0%) 1/20 (5%) 0/19 (0%)
Drug withdrawal syndrome 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Face oedema 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Local swelling 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Oedema peripheral 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Hepatobiliary disorders
Jaundice 1/5 (20%) 0/20 (0%) 0/19 (0%)
Cholelithiasis 0/5 (0%) 1/20 (5%) 0/19 (0%)
Hyperbilirubinaemia 0/5 (0%) 1/20 (5%) 0/19 (0%)
Infections and infestations
Oral candidiasis 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Oral herpes 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Pneumonia 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Candiduria 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Clostridium difficile infection 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Fungal skin infection 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Hepatitis C 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Nasal herpes 0/5 (0%) 1/20 (5%) 0/19 (0%)
Pneumonia klebsiella 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Pneumonia pseudomonal 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Urinary tract infection 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Injury, poisoning and procedural complications
Contusion 1/5 (20%) 0/20 (0%) 0/19 (0%)
Fall 0/5 (0%) 1/20 (5%) 0/19 (0%)
Laceration 0/5 (0%) 1/20 (5%) 0/19 (0%)
Penis injury 0/5 (0%) 1/20 (5%) 0/19 (0%)
Wound 0/5 (0%) 1/20 (5%) 0/19 (0%)
Investigations
Blood calcium decreased 1/5 (20%) 0/20 (0%) 0/19 (0%)
Blood magnesium decreased 1/5 (20%) 0/20 (0%) 0/19 (0%)
Blood phosphorus decreased 1/5 (20%) 0/20 (0%) 0/19 (0%)
Blood sodium increased 1/5 (20%) 0/20 (0%) 0/19 (0%)
Body temperature increased 1/5 (20%) 0/20 (0%) 0/19 (0%)
Oxygen saturation decreased 1/5 (20%) 0/20 (0%) 0/19 (0%)
Alanine aminotransferase increased 0/5 (0%) 1/20 (5%) 2/19 (10.5%)
Aspartate aminotransferase increased 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Haemoglobin decreased 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Activated partial thromboplastin time prolonged 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Blood creatine phosphokinase increased 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Blood lactate dehydrogenase increased 0/5 (0%) 1/20 (5%) 0/19 (0%)
Blood pH increased 0/5 (0%) 1/20 (5%) 0/19 (0%)
Blood potassium decreased 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Blood pressure increased 0/5 (0%) 1/20 (5%) 0/19 (0%)
Blood sodium increased 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Electrocardiogram QT prolonged 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Gamma-glutamyltransferase increased 0/5 (0%) 1/20 (5%) 0/19 (0%)
Platelet count increased 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Respiratory rate increased 0/5 (0%) 1/20 (5%) 0/19 (0%)
Urine output decreased 0/5 (0%) 1/20 (5%) 0/19 (0%)
White blood cell count increased 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Metabolism and nutrition disorders
Acidosis 1/5 (20%) 1/20 (5%) 0/19 (0%)
Hyperglycaemia 1/5 (20%) 1/20 (5%) 0/19 (0%)
Hypokalaemia 0/5 (0%) 5/20 (25%) 6/19 (31.6%)
Hypernatraemia 0/5 (0%) 0/20 (0%) 4/19 (21.1%)
Hypoglycaemia 0/5 (0%) 3/20 (15%) 1/19 (5.3%)
Food intolerance 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Hypochloraemia 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Hypophosphataemia 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Fluid overload 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Hyperkalaemia 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Hypomagnesaemia 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Metabolic acidosis 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Metabolic alkalosis 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Back pain 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Nervous system disorders
Headache 1/5 (20%) 2/20 (10%) 2/19 (10.5%)
Encephalopathy 0/5 (0%) 0/20 (0%) 2/19 (10.5%)
Dizziness 0/5 (0%) 1/20 (5%) 0/19 (0%)
Psychiatric disorders
Agitation 1/5 (20%) 4/20 (20%) 5/19 (26.3%)
Insomnia 1/5 (20%) 2/20 (10%) 3/19 (15.8%)
Delirium 0/5 (0%) 3/20 (15%) 4/19 (21.1%)
Confusional state 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Hallucination 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Suicidal ideation 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Renal and urinary disorders
Renal failure 0/5 (0%) 1/20 (5%) 1/19 (5.3%)
Renal failure acute 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Reproductive system and breast disorders
Scrotal erythema 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Scrotal oedema 0/5 (0%) 1/20 (5%) 0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis 1/5 (20%) 0/20 (0%) 1/19 (5.3%)
Pneumothorax 1/5 (20%) 1/20 (5%) 0/19 (0%)
Respiratory failure 1/5 (20%) 0/20 (0%) 1/19 (5.3%)
Pleural effusion 0/5 (0%) 3/20 (15%) 0/19 (0%)
Acute respiratory distress syndrome 0/5 (0%) 1/20 (5%) 0/19 (0%)
Atelectasis 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Haemoptysis 0/5 (0%) 1/20 (5%) 0/19 (0%)
Hiccups 0/5 (0%) 1/20 (5%) 0/19 (0%)
Increased upper airway secretion 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Laryngeal oedema 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Pleuritic pain 0/5 (0%) 1/20 (5%) 0/19 (0%)
Skin and subcutaneous tissue disorders
Rash 0/5 (0%) 1/20 (5%) 3/19 (15.8%)
Blister 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Blood blister 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Erythema 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Rash macular 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Rash papular 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Subcutaneous emphysema 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Swelling face 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Surgical and medical procedures
Endotracheal intubation 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Vascular disorders
Hypertension 0/5 (0%) 2/20 (10%) 1/19 (5.3%)
Deep vein thrombosis 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Haematoma 0/5 (0%) 0/20 (0%) 1/19 (5.3%)
Hypotension 0/5 (0%) 1/20 (5%) 0/19 (0%)
Thrombophlebitis 0/5 (0%) 1/20 (5%) 0/19 (0%)
Thrombophlebitis superficial 0/5 (0%) 0/20 (0%) 1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01597635
Other Study ID Numbers:
  • 114622
First Posted:
May 14, 2012
Last Update Posted:
Sep 28, 2017
Last Verified:
Aug 1, 2017