Lung Injury, Acute
Conditions
Keywords
rhACE2, Acute Respiratory Distress Syndrome (ARDS), Acute Lung Injury, GSK2586881, critical care
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.
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.
Interventions
DRUGDose 1 GSK2586881
Low dose GSK2586881 administered intravenously
DRUGDose 2 GSK2586881
Medium dose GSK2586881 administered intravenously
DRUGDose 3 GSK2586881
Medium-High dose GSK2586881 administered intravenously
DRUGDose 4 GSK2586881
High dose GSK2586881 administered intravenously
DRUGPlacebo (saline)
Administered intravenously to match intervention
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part A 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. | 5 |
| Part B (Placebo BID) Eligible participants received intravenous matching placebo (saline solution) BID as a slow infusion over 3-5 minutes for 3 days. | 20 |
| Part B (GSK2586881 BID) Eligible participants received intravenous dose of 0.4 mg/kg BID of GSK2586881 as a slow infusion over 3-5 minutes for 3 days. | 19 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A | Adverse Event | 3 | 0 | 0 |
| Part B | Adverse Event | 0 | 0 | 1 |
| Part B | Protocol-defined stopping criteria | 0 | 4 | 3 |
| Part B | Protocol Violation | 0 | 1 | 0 |
| Part B | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A | Part B (Placebo BID) | Part B (GSK2586881 BID) | Total |
|---|---|---|---|---|
| Age, Customized 18-80 years | 5 Participants | 20 Participants | 19 Participants | 44 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 17 Participants | 18 Participants | 40 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 3 Participants | 13 Participants | 13 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 5 | 2 / 20 | 1 / 19 |
| other Total, other adverse events | 5 / 5 | 14 / 20 | 15 / 19 |
| serious Total, serious adverse events | 3 / 5 | 4 / 20 | 3 / 19 |
Outcome results
Primary
Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Albumin on Day 1 at Pre-dose | 25.6 grams per liter | Standard Deviation 2.19 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Albumin on Day 3 at 12 hours | 25.5 grams per liter | Standard Deviation 5.05 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Albumin on Follow-up Day 7 | 27.9 grams per liter | Standard Deviation 6.62 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Total protein on Day 1 at Pre-dose | 54.60 grams per liter | Standard Deviation 5.983 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Total protein on Day 3 at 12 hours | 55.06 grams per liter | Standard Deviation 7.122 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Total protein on Follow-up Day 7 | 60.86 grams per liter | Standard Deviation 8.646 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Total protein on Day 3 at 12 hours | 52.12 grams per liter | Standard Deviation 7.457 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Albumin on Day 1 at Pre-dose | 18.6 grams per liter | Standard Deviation 3.21 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Total protein on Day 1 at Pre-dose | 50.20 grams per liter | Standard Deviation 2.775 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Albumin on Day 3 at 12 hours | 22.3 grams per liter | Standard Deviation 4.88 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Total protein on Follow-up Day 7 | 58.18 grams per liter | Standard Deviation 10.323 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Albumin and Total Protein Assessment Upto Day 7 (Part B) | Albumin on Follow-up Day 7 | 25.5 grams per liter | Standard Deviation 6.27 |
Primary
Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alkaline phosphatase on Day 3 at 12 hours | 130.9 International units per liter | Standard Deviation 68.16 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alkaline phosphatase on Follow-up Day 7 | 101.1 International units per liter | Standard Deviation 40.15 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alanine amino transferase on Day 1 at Pre-dose | 101.8 International units per liter | Standard Deviation 105.98 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alanine amino transferase on Day 3 at 12 hours | 73.4 International units per liter | Standard Deviation 71.27 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alanine amino transferase on Follow-up Day 7 | 44.9 International units per liter | Standard Deviation 42.74 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Asparatate amino transferase on Day 1 at Pre-dose | 96.8 International units per liter | Standard Deviation 46.09 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Asparatate amino transferase on Day 3 at 12 hours | 56.2 International units per liter | Standard Deviation 34.6 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Asparatate amino transferase on Follow-up Day 7 | 35.6 International units per liter | Standard Deviation 20.25 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Gamma glutamyl transferase on Day 1 at Pre-dose | 96.0 International units per liter | Standard Deviation 22.63 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Gamma glutamyl transferase on Day 3 at 12 hours | 156.5 International units per liter | Standard Deviation 149.89 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Gamma glutamyl transferase on Follow-up Day 7 | 116.4 International units per liter | Standard Deviation 105.36 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alkaline phosphatase on Day 1 at Pre-dose | 76.6 International units per liter | Standard Deviation 18.57 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Gamma glutamyl transferase on Follow-up Day 7 | 143.0 International units per liter | Standard Deviation 138.22 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alkaline phosphatase on Day 3 at 12 hours | 109.2 International units per liter | Standard Deviation 63.02 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Asparatate amino transferase on Day 3 at 12 hours | 62.0 International units per liter | Standard Deviation 71.54 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alkaline phosphatase on Follow-up Day 7 | 117.0 International units per liter | Standard Deviation 56.07 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Gamma glutamyl transferase on Day 3 at 12 hours | 98.4 International units per liter | Standard Deviation 71.85 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alanine amino transferase on Day 1 at Pre-dose | 56.8 International units per liter | Standard Deviation 42.2 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Asparatate amino transferase on Follow-up Day 7 | 76.5 International units per liter | Standard Deviation 106.39 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alanine amino transferase on Day 3 at 12 hours | 43.6 International units per liter | Standard Deviation 50.72 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alkaline phosphatase on Day 1 at Pre-dose | 94.0 International units per liter | Standard Deviation 50.86 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Alanine amino transferase on Follow-up Day 7 | 117.9 International units per liter | Standard Deviation 224.94 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Gamma glutamyl transferase on Day 1 at Pre-dose | 40.7 International units per liter | Standard Deviation 25.89 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Alkaline Phosphatase, Asparatate Amino Transferase, Alanine Amino Transferase, Gamma Glutamyl Transferase Assessment Upto Day 7 (Part B) | Asparatate amino transferase on Day 1 at Pre-dose | 64.6 International units per liter | Standard Deviation 37.14 |
Primary
Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Calcium on Day 1 at Pre-dose | 1.927 millimoles per liter | Standard Deviation 0.0736 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Calcium on Day 3 at 12 hours | 1.983 millimoles per liter | Standard Deviation 0.122 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Calcium on Follow-up Day 7 | 2.155 millimoles per liter | Standard Deviation 0.1016 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Chloride on Day 1 at Pre-dose | 108.8 millimoles per liter | Standard Deviation 5.93 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Chloride on Day 3 at 12 hours | 107.7 millimoles per liter | Standard Deviation 5.12 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Chloride on Follow-up Day 7 | 104.4 millimoles per liter | Standard Deviation 3.76 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Carbon dioxide on Day 1 at Pre-dose | 24.40 millimoles per liter | Standard Deviation 5.273 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Carbon dioxide on Day 3 at 12 hours | 26.35 millimoles per liter | Standard Deviation 3.176 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Carbon dioxide on Follow-up Day 7 | 27.69 millimoles per liter | Standard Deviation 3.728 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Glucose on Day 1 at Pre-dose | 6.015 millimoles per liter | Standard Deviation 0.7499 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Glucose on Day 3 at 12 hours | 8.095 millimoles per liter | Standard Deviation 2.1569 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Glucose on Follow-up Day 7 | 6.701 millimoles per liter | Standard Deviation 1.6354 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Potassium on Day 1 at Pre-dose | 3.88 millimoles per liter | Standard Deviation 0.444 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Potassium on Day 3 at 12 hours | 4.20 millimoles per liter | Standard Deviation 0.511 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Potassium on Follow-up Day 7 | 3.83 millimoles per liter | Standard Deviation 0.505 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Sodium on Day 1 at Pre-dose | 141.8 millimoles per liter | Standard Deviation 3.11 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Sodium on Day 3 at 12 hours | 143.1 millimoles per liter | Standard Deviation 4.46 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Sodium on Follow-up Day 7 | 141.9 millimoles per liter | Standard Deviation 4.59 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Urea/Blood urea nitrogen on Day 1 at Pre-dose | 6.433 millimoles per liter | Standard Deviation 3.0512 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Urea/Blood urea nitrogen on Day 3 at 12 hours | 10.410 millimoles per liter | Standard Deviation 6.5542 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Urea/Blood urea nitrogen on Follow-up Day 7 | 11.787 millimoles per liter | Standard Deviation 9.3546 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Glucose on Day 3 at 12 hours | 7.411 millimoles per liter | Standard Deviation 1.6158 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Calcium on Day 1 at Pre-dose | 1.894 millimoles per liter | Standard Deviation 0.107 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Urea/Blood urea nitrogen on Day 1 at Pre-dose | 11.399 millimoles per liter | Standard Deviation 7.4163 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Calcium on Day 3 at 12 hours | 1.982 millimoles per liter | Standard Deviation 0.1296 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Glucose on Follow-up Day 7 | 7.285 millimoles per liter | Standard Deviation 1.5159 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Calcium on Follow-up Day 7 | 2.104 millimoles per liter | Standard Deviation 0.1448 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Sodium on Day 3 at 12 hours | 141.6 millimoles per liter | Standard Deviation 4.03 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Chloride on Day 1 at Pre-dose | 104.0 millimoles per liter | Standard Deviation 7.18 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Potassium on Day 1 at Pre-dose | 3.72 millimoles per liter | Standard Deviation 0.164 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Chloride on Day 3 at 12 hours | 106.0 millimoles per liter | Standard Deviation 6.05 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Urea/Blood urea nitrogen on Follow-up Day 7 | 9.207 millimoles per liter | Standard Deviation 6.5375 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Chloride on Follow-up Day 7 | 103.7 millimoles per liter | Standard Deviation 5.01 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Potassium on Day 3 at 12 hours | 3.96 millimoles per liter | Standard Deviation 0.578 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Carbon dioxide on Day 1 at Pre-dose | 23.28 millimoles per liter | Standard Deviation 6.685 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Sodium on Follow-up Day 7 | 139.7 millimoles per liter | Standard Deviation 4.58 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Carbon dioxide on Day 3 at 12 hours | 27.83 millimoles per liter | Standard Deviation 6.071 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Potassium on Follow-up Day 7 | 3.92 millimoles per liter | Standard Deviation 0.435 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Carbon dioxide on Follow-up Day 7 | 27.39 millimoles per liter | Standard Deviation 3.412 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Urea/Blood urea nitrogen on Day 3 at 12 hours | 9.485 millimoles per liter | Standard Deviation 6.5777 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Glucose on Day 1 at Pre-dose | 6.159 millimoles per liter | Standard Deviation 1.123 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen Assessment Upto Day 7 (Part B) | Sodium on Day 1 at Pre-dose | 137.6 millimoles per liter | Standard Deviation 3.71 |
Primary
Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Direct bilirubin on Day 1 at Pre-dose | 10.663 micromoles per liter | Standard Deviation 7.8146 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Direct bilirubin on Day 3 at 12 hours | 10.446 micromoles per liter | Standard Deviation 14.2406 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Direct bilirubin on Follow-up Day 7 | 4.140 micromoles per liter | Standard Deviation 3.5564 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Total bilirubin on Day 1 at Pre-dose | 16.672 micromoles per liter | Standard Deviation 11.1375 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Total bilirubin on Day 3 at 12 hours | 16.803 micromoles per liter | Standard Deviation 15.8462 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Total bilirubin on Follow-up Day 7 | 12.547 micromoles per liter | Standard Deviation 10.7837 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Creatinine on Day 1 at Pre-dose | 85.194 micromoles per liter | Standard Deviation 19.9261 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Creatinine on Day 3 at 12 hours | 108.189 micromoles per liter | Standard Deviation 102.4388 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Creatinine on Follow-up Day 7 | 91.726 micromoles per liter | Standard Deviation 45.2713 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Uric acid on Day 1 at Pre-dose | 233.432 micromoles per liter | Standard Deviation 67.9909 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Uric acid on Day 3 at 12 hours | 192.925 micromoles per liter | Standard Deviation 143.7971 |
| Part B (Placebo BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Uric acid on Follow-up Day 7 | 241.766 micromoles per liter | Standard Deviation 72.0137 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Uric acid on Day 3 at 12 hours | 228.144 micromoles per liter | Standard Deviation 134.9558 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Direct bilirubin on Day 1 at Pre-dose | 13.792 micromoles per liter | Standard Deviation 17.7932 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Creatinine on Day 1 at Pre-dose | 126.228 micromoles per liter | Standard Deviation 71.9085 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Direct bilirubin on Day 3 at 12 hours | 10.428 micromoles per liter | Standard Deviation 22.4573 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Uric acid on Day 1 at Pre-dose | 181.453 micromoles per liter | Standard Deviation 203.5924 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Direct bilirubin on Follow-up Day 7 | 2.576 micromoles per liter | Standard Deviation 1.6103 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Creatinine on Day 3 at 12 hours | 103.066 micromoles per liter | Standard Deviation 90.6252 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Total bilirubin on Day 1 at Pre-dose | 21.926 micromoles per liter | Standard Deviation 20.4768 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Uric acid on Follow-up Day 7 | 225.326 micromoles per liter | Standard Deviation 144.4626 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Total bilirubin on Day 3 at 12 hours | 14.119 micromoles per liter | Standard Deviation 24.8465 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Creatinine on Follow-up Day 7 | 90.516 micromoles per liter | Standard Deviation 71.8052 |
| Part B (GSK2586881 BID) | Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Assessment Upto Day 7 (Part B) | Total bilirubin on Follow-up Day 7 | 5.818 micromoles per liter | Standard Deviation 3.0149 |
Primary
Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at Pre-dose | 122.0 Millimeters of merucry | Standard Deviation 18.97 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 12 hours | 64.3 Millimeters of merucry | Standard Deviation 12.78 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 0.5 hours | 118.8 Millimeters of merucry | Standard Deviation 20.01 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 2 hours | 65.2 Millimeters of merucry | Standard Deviation 10.34 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 2 hours | 122.9 Millimeters of merucry | Standard Deviation 14.85 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 0.5 hours | 64.4 Millimeters of merucry | Standard Deviation 13.75 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 6 hours | 121.6 Millimeters of merucry | Standard Deviation 17.8 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 6 hours | 65.2 Millimeters of merucry | Standard Deviation 13.83 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 12 hours | 122.9 Millimeters of merucry | Standard Deviation 21.88 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 2 at 0 hours | 67.0 Millimeters of merucry | Standard Deviation 15.17 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 2 at 0 hours | 131.6 Millimeters of merucry | Standard Deviation 23.68 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 12 hours | 70.0 Millimeters of merucry | Standard Deviation 16.4 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 0 hours | 124.4 Millimeters of merucry | Standard Deviation 16.32 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 6 hours | 63.4 Millimeters of merucry | Standard Deviation 12.08 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 0.5 hours | 127.1 Millimeters of merucry | Standard Deviation 15.76 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 18 hours | 73.2 Millimeters of merucry | Standard Deviation 16.31 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 2 hours | 125.2 Millimeters of merucry | Standard Deviation 14.77 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 0 hours | 63.9 Millimeters of merucry | Standard Deviation 14.5 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 6 hours | 127.8 Millimeters of merucry | Standard Deviation 19.01 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 24 hours | 66.4 Millimeters of merucry | Standard Deviation 15.19 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 12 hours | 130.2 Millimeters of merucry | Standard Deviation 21.95 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 2 hours | 64.4 Millimeters of merucry | Standard Deviation 12.59 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 18 hours | 137.5 Millimeters of merucry | Standard Deviation 23.92 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on follow-up Day 7 | 66.4 Millimeters of merucry | Standard Deviation 11.58 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 24 hours | 128.8 Millimeters of merucry | Standard Deviation 20.43 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 0.5 hours | 65.6 Millimeters of merucry | Standard Deviation 13.21 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on follow-up Day 7 | 129.1 Millimeters of merucry | Standard Deviation 22.22 |
| Part B (Placebo BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at Pre-dose | 64.7 Millimeters of merucry | Standard Deviation 12.86 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on follow-up Day 7 | 129.9 Millimeters of merucry | Standard Deviation 17.92 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at Pre-dose | 53.9 Millimeters of merucry | Standard Deviation 10.36 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 0.5 hours | 54.3 Millimeters of merucry | Standard Deviation 11.39 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 2 hours | 54.8 Millimeters of merucry | Standard Deviation 9.6 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 6 hours | 57.1 Millimeters of merucry | Standard Deviation 9.21 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 1 at 12 hours | 57.6 Millimeters of merucry | Standard Deviation 10.05 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 2 at 0 hours | 57.0 Millimeters of merucry | Standard Deviation 10.22 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 0 hours | 62.7 Millimeters of merucry | Standard Deviation 14.03 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 0.5 hours | 61.1 Millimeters of merucry | Standard Deviation 12.83 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 2 hours | 58.1 Millimeters of merucry | Standard Deviation 11.2 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 6 hours | 62.2 Millimeters of merucry | Standard Deviation 16.59 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 12 hours | 60.6 Millimeters of merucry | Standard Deviation 13.2 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 18 hours | 61.8 Millimeters of merucry | Standard Deviation 10.5 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on Day 3 at 24 hours | 61.1 Millimeters of merucry | Standard Deviation 13.06 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Diastolic blood pressure on follow-up Day 7 | 62.7 Millimeters of merucry | Standard Deviation 8.52 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at Pre-dose | 106.1 Millimeters of merucry | Standard Deviation 12.68 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 0.5 hours | 105.7 Millimeters of merucry | Standard Deviation 12.66 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 2 hours | 107.5 Millimeters of merucry | Standard Deviation 20.49 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 6 hours | 118.7 Millimeters of merucry | Standard Deviation 16.41 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 1 at 12 hours | 116.9 Millimeters of merucry | Standard Deviation 24.33 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 2 at 0 hours | 114.8 Millimeters of merucry | Standard Deviation 18.94 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 0 hours | 125.2 Millimeters of merucry | Standard Deviation 23.7 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 0.5 hours | 121.9 Millimeters of merucry | Standard Deviation 23.6 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 2 hours | 118.5 Millimeters of merucry | Standard Deviation 20.87 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 6 hours | 118.5 Millimeters of merucry | Standard Deviation 19.6 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 12 hours | 123.2 Millimeters of merucry | Standard Deviation 24.61 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 18 hours | 129.0 Millimeters of merucry | Standard Deviation 17.45 |
| Part B (GSK2586881 BID) | Diastolic and Systolic Blood Pressure Assessments Upto Day 7 (Part B) | Systolic blood pressure on Day 3 at 24 hours | 130.3 Millimeters of merucry | Standard Deviation 24.97 |
Primary
Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Basett) on Day 3,12 hours | 438.9 millisecond | Standard Deviation 13.02 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QRS duration at follow-up Day 7 | 84.4 millisecond | Standard Deviation 9.01 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Basett) at follow-up Day 7 | 453.5 millisecond | Standard Deviation 31.57 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Fridericia), Day 1,Pre-dose | 423.4 millisecond | — |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | PR interval on Day 3,12 hours | 128.5 millisecond | Standard Deviation 42.09 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Fridericia), Day 3,12 hours | 406.3 millisecond | Standard Deviation 20.18 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Uncorrected QT interval on Day 1,Pre-dose | 350.0 millisecond | Standard Deviation 27.96 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Fridericia),follow-up Day 7 | 419.5 millisecond | Standard Deviation 12.66 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QRS duration on Day 1,Pre-dose | 98.0 millisecond | Standard Deviation 9.27 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QTCU on Day 1,Pre-dose | 458.3 millisecond | Standard Deviation 8.81 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Uncorrected QT interval on Day 3,12 hours | 357.8 millisecond | Standard Deviation 48.9 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QTCU on Day 3,12 hours | 440.3 millisecond | Standard Deviation 40.07 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | PR interval on Day 1,Pre-dose | 136.8 millisecond | Standard Deviation 24.19 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QTCU at follow-up Day 7 | 441.6 millisecond | Standard Deviation 17.72 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Uncorrected QT interval at follow-up Day 7 | 354.3 millisecond | Standard Deviation 37.12 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | RR interval on Day 1,Pre-dose | 584.6 millisecond | — |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QRS duration on Day 3,12 hours | 82.8 millisecond | Standard Deviation 8.66 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | RR interval on Day 3,12 hours | 638.8 millisecond | Standard Deviation 135.85 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Basett) on Day 1,Pre-dose | 463.0 millisecond | — |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | RR interval at follow-up Day 7 | 661.7 millisecond | Standard Deviation 203.97 |
| Part B (Placebo BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | PR interval at follow-up | 140.4 millisecond | Standard Deviation 17.81 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | RR interval at follow-up Day 7 | 582.9 millisecond | Standard Deviation 128.96 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | PR interval on Day 1,Pre-dose | 139.0 millisecond | Standard Deviation 25.09 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | PR interval on Day 3,12 hours | 149.3 millisecond | Standard Deviation 19.76 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | PR interval at follow-up | 144.8 millisecond | Standard Deviation 20.73 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QRS duration on Day 1,Pre-dose | 95.5 millisecond | Standard Deviation 16.62 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QRS duration on Day 3,12 hours | 98.8 millisecond | Standard Deviation 15.86 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QRS duration at follow-up Day 7 | 88.6 millisecond | Standard Deviation 16.86 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Uncorrected QT interval on Day 1,Pre-dose | 357.5 millisecond | Standard Deviation 44.13 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Uncorrected QT interval on Day 3,12 hours | 369.8 millisecond | Standard Deviation 33.92 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Uncorrected QT interval at follow-up Day 7 | 377.5 millisecond | Standard Deviation 49.46 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Basett) on Day 1,Pre-dose | 469.4 millisecond | Standard Deviation 66.08 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Basett) on Day 3,12 hours | 468.9 millisecond | Standard Deviation 41.59 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Fridericia), Day 1,Pre-dose | 418.1 millisecond | Standard Deviation 49.03 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Fridericia), Day 3,12 hours | 432.7 millisecond | Standard Deviation 35.92 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Fridericia),follow-up Day 7 | 439.6 millisecond | Standard Deviation 36.29 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QTCU on Day 1,Pre-dose | 447.3 millisecond | Standard Deviation 27.65 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QTCU on Day 3,12 hours | 445.4 millisecond | Standard Deviation 28.11 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | QTCU at follow-up Day 7 | 457.3 millisecond | Standard Deviation 26.12 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | RR interval on Day 1,Pre-dose | 513.6 millisecond | Standard Deviation 97.25 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | RR interval on Day 3,12 hours | 623.2 millisecond | Standard Deviation 76.02 |
| Part B (GSK2586881 BID) | Electrocardiogram (ECG) Parameters, Including PR, QRS, QT, and QTCU and RR Intervals Upto Day 7 (Part B) | Corrected QT interval(Basett) at follow-up Day 7 | 483.5 millisecond | Standard Deviation 46.51 |
Primary
Heart Rate Assessments Upto Day 7 (Part B)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 2 at 0 hours | 92.2 Beats per minute | Standard Deviation 19.02 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 6 hours | 93.2 Beats per minute | Standard Deviation 16.63 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 6 hours | 90.0 Beats per minute | Standard Deviation 18.03 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 12 hours | 93.8 Beats per minute | Standard Deviation 20.12 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 18 hours | 98.1 Beats per minute | Standard Deviation 19.34 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 24 hours | 90.8 Beats per minute | Standard Deviation 15.46 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 0 hours | 93.3 Beats per minute | Standard Deviation 19.2 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate at follow-up Day 7 | 91.6 Beats per minute | Standard Deviation 19.06 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 2 hours | 88.8 Beats per minute | Standard Deviation 18.22 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 0.5 hours | 91.7 Beats per minute | Standard Deviation 16.29 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at Pre-dose | 87.4 Beats per minute | Standard Deviation 16.32 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 12 hours | 87.6 Beats per minute | Standard Deviation 20.6 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 0.5 hours | 87.9 Beats per minute | Standard Deviation 17.08 |
| Part B (Placebo BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 2 hours | 93.2 Beats per minute | Standard Deviation 16.51 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 0.5 hours | 95.3 Beats per minute | Standard Deviation 15.1 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 2 hours | 94.7 Beats per minute | Standard Deviation 17.59 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 6 hours | 96.5 Beats per minute | Standard Deviation 18.58 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at 12 hours | 97.1 Beats per minute | Standard Deviation 18.46 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 2 at 0 hours | 93.4 Beats per minute | Standard Deviation 16.98 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 0 hours | 97.7 Beats per minute | Standard Deviation 14.11 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 0.5 hours | 97.2 Beats per minute | Standard Deviation 12.81 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 2 hours | 95.2 Beats per minute | Standard Deviation 13.31 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 6 hours | 97.5 Beats per minute | Standard Deviation 14.44 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 24 hours | 95.1 Beats per minute | Standard Deviation 13.25 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate at follow-up Day 7 | 94.2 Beats per minute | Standard Deviation 15.17 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 18 hours | 88.9 Beats per minute | Standard Deviation 15.69 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 1 at Pre-dose | 97.7 Beats per minute | Standard Deviation 16.25 |
| Part B (GSK2586881 BID) | Heart Rate Assessments Upto Day 7 (Part B) | Heart rate on Day 3 at 12 hours | 93.6 Beats per minute | Standard Deviation 16.08 |
Primary
Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) | Hematocrit on Day 1 at Pre-dose | 0.201 Fraction | Standard Deviation 0.1666 |
| Part B (Placebo BID) | Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) | Hematocrit on Day 3 at 12 hours | 0.271 Fraction | Standard Deviation 0.1071 |
| Part B (Placebo BID) | Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) | Hematocrit on Follow-up Day 7 | 0.254 Fraction | Standard Deviation 0.1298 |
| Part B (GSK2586881 BID) | Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) | Hematocrit on Day 1 at Pre-dose | 0.196 Fraction | Standard Deviation 0.1333 |
| Part B (GSK2586881 BID) | Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) | Hematocrit on Day 3 at 12 hours | 1.519 Fraction | Standard Deviation 5.3867 |
| Part B (GSK2586881 BID) | Hematology Parameter Hematocrit Assessment Upto Day 7 (Part B) | Hematocrit on Follow-up Day 7 | 2.270 Fraction | Standard Deviation 7.5504 |
Primary
Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | Hemoglobin on Day 1 at Pre-dose | 99.5 grams per liter | Standard Deviation 24.83 |
| Part B (Placebo BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | Hemoglobin on Day 3 at 12 hours | 195.8 grams per liter | Standard Deviation 286.77 |
| Part B (Placebo BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | Hemoglobin on Follow-up Day 7 | 244.7 grams per liter | Standard Deviation 401.03 |
| Part B (Placebo BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | MCHC on Day 1 at Pre-dose | 331.8 grams per liter | Standard Deviation 10.68 |
| Part B (Placebo BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | MCHC on Day 3 at 12 hours | 328.4 grams per liter | Standard Deviation 14.73 |
| Part B (Placebo BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | MCHC on Follow-up Day 7 | 327.8 grams per liter | Standard Deviation 12.35 |
| Part B (GSK2586881 BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | MCHC on Day 3 at 12 hours | 330.8 grams per liter | Standard Deviation 16.82 |
| Part B (GSK2586881 BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | Hemoglobin on Day 1 at Pre-dose | 84.0 grams per liter | Standard Deviation 13.09 |
| Part B (GSK2586881 BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | MCHC on Day 1 at Pre-dose | 339.5 grams per liter | Standard Deviation 19.12 |
| Part B (GSK2586881 BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | Hemoglobin on Day 3 at 12 hours | 180.8 grams per liter | Standard Deviation 266.16 |
| Part B (GSK2586881 BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | MCHC on Follow-up Day 7 | 325.4 grams per liter | Standard Deviation 6.82 |
| Part B (GSK2586881 BID) | Hematology Parameter Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Assessment Upto Day 7 (Part B) | Hemoglobin on Follow-up Day 7 | 213.6 grams per liter | Standard Deviation 301.5 |
Primary
Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) | MCH on Day 1 at Pre-dose | 30.30 picograms | Standard Deviation 4.493 |
| Part B (Placebo BID) | Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) | MCH on Day 3 at 12 hours | 30.02 picograms | Standard Deviation 2.695 |
| Part B (Placebo BID) | Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) | MCH on Follow-up Day 7 | 30.49 picograms | Standard Deviation 2.545 |
| Part B (GSK2586881 BID) | Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) | MCH on Day 1 at Pre-dose | 30.40 picograms | Standard Deviation 0.361 |
| Part B (GSK2586881 BID) | Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) | MCH on Day 3 at 12 hours | 30.32 picograms | Standard Deviation 1.955 |
| Part B (GSK2586881 BID) | Hematology Parameter Mean Corpuscle Hemoglobin (MCH) Assessment Upto Day 7 (Part B) | MCH on Follow-up Day 7 | 30.25 picograms | Standard Deviation 2.071 |
Primary
Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) | MCV on Day 1 at Pre-dose | 77.37 femtoliters | Standard Deviation 33.654 |
| Part B (Placebo BID) | Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) | MCV on Day 3 at 12 hours | 91.28 femtoliters | Standard Deviation 5.611 |
| Part B (Placebo BID) | Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) | MCV on Follow-up Day 7 | 92.53 femtoliters | Standard Deviation 7.234 |
| Part B (GSK2586881 BID) | Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) | MCV on Day 1 at Pre-dose | 93.87 femtoliters | Standard Deviation 0.971 |
| Part B (GSK2586881 BID) | Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) | MCV on Day 3 at 12 hours | 90.69 femtoliters | Standard Deviation 5.976 |
| Part B (GSK2586881 BID) | Hematology Parameter Mean Corpuscle Volume (MCV) Assessment Upto Day 7 (Part B) | MCV on Follow-up Day 7 | 90.46 femtoliters | Standard Deviation 7.063 |
Primary
Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Eosinophils on Follow-up Day 7 | 0.137 giga per liter | Standard Deviation 0.1074 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Basophils on Day 1 at Pre-dose | 0.020 giga per liter | — |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Lymphocytes on Day 1 at Pre-dose | 4.81 giga per liter | Standard Deviation 4.603 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Platelet count on Follow-up Day 7 | 334.1 giga per liter | Standard Deviation 169.06 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Lymphocytes on Day 3 at 12 hours | 1.08 giga per liter | Standard Deviation 0.948 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Basophils on Day 3 at 12 hours | 0.015 giga per liter | Standard Deviation 0.0296 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Lymphocytes on Follow-up Day 7 | 1.61 giga per liter | Standard Deviation 1.244 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | White blood cell count on Day 3 at 12 hours | 14.82 giga per liter | Standard Deviation 5.927 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Monocytes on Day 1 at Pre-dose | 1.760 giga per liter | Standard Deviation 1.7112 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Basophils on Follow-up Day 7 | 0.025 giga per liter | Standard Deviation 0.0431 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Monocytes on Day 3 at 12 hours | 0.503 giga per liter | Standard Deviation 0.4046 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Platelet count on Day 3 at 12 hours | 218.9 giga per liter | Standard Deviation 120.68 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Monocytes on Follow-up Day 7 | 0.669 giga per liter | Standard Deviation 0.3986 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Eosinophils on Day 1 at Pre-dose | 0.110 giga per liter | — |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Total neutrophils on Day 1 at Pre-dose | 6.990 giga per liter | Standard Deviation 4.5113 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | White blood cell count on Follow-up Day 7 | 14.09 giga per liter | Standard Deviation 5.197 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Total neutrophils on Day 3 at 12 hours | 11.563 giga per liter | Standard Deviation 6.0785 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Eosinophils on Day 3 at 12 hours | 0.096 giga per liter | Standard Deviation 0.1624 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Total neutrophils on Follow-up Day 7 | 16.775 giga per liter | Standard Deviation 21.6419 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | White blood cell count on Day 1 at Pre-dose | 15.15 giga per liter | Standard Deviation 14.289 |
| Part B (Placebo BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Platelet count on Day 1 at Pre-dose | 170.3 giga per liter | Standard Deviation 67.26 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Lymphocytes on Day 3 at 12 hours | 0.60 giga per liter | Standard Deviation 0.38 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Platelet count on Day 3 at 12 hours | 235.9 giga per liter | Standard Deviation 134.43 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Platelet count on Follow-up Day 7 | 369.8 giga per liter | Standard Deviation 169.7 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | White blood cell count on Day 1 at Pre-dose | 10.72 giga per liter | Standard Deviation 8.829 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | White blood cell count on Day 3 at 12 hours | 11.82 giga per liter | Standard Deviation 6.618 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | White blood cell count on Follow-up Day 7 | 36.56 giga per liter | Standard Deviation 84.293 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Basophils on Day 1 at Pre-dose | 0.000 giga per liter | Standard Deviation 0 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Basophils on Day 3 at 12 hours | 0.011 giga per liter | Standard Deviation 0.0277 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Basophils on Follow-up Day 7 | 0.113 giga per liter | Standard Deviation 0.1848 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Eosinophils on Day 1 at Pre-dose | 0.233 giga per liter | Standard Deviation 0.4041 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Eosinophils on Day 3 at 12 hours | 0.163 giga per liter | Standard Deviation 0.228 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Eosinophils on Follow-up Day 7 | 0.324 giga per liter | Standard Deviation 0.4957 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Lymphocytes on Day 1 at Pre-dose | 0.52 giga per liter | Standard Deviation 0.266 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Platelet count on Day 1 at Pre-dose | 236.0 giga per liter | Standard Deviation 158.73 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Lymphocytes on Follow-up Day 7 | 1.04 giga per liter | Standard Deviation 0.663 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Monocytes on Day 1 at Pre-dose | 0.377 giga per liter | Standard Deviation 0.3356 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Monocytes on Day 3 at 12 hours | 0.571 giga per liter | Standard Deviation 0.6336 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Monocytes on Follow-up Day 7 | 0.727 giga per liter | Standard Deviation 0.5812 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Total neutrophils on Day 1 at Pre-dose | 7.807 giga per liter | Standard Deviation 9.3471 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Total neutrophils on Day 3 at 12 hours | 9.931 giga per liter | Standard Deviation 6.8583 |
| Part B (GSK2586881 BID) | Hematology Parameters Basophils, Eosinophil, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count Upto Day 7 (Part B) | Total neutrophils on Follow-up Day 7 | 11.761 giga per liter | Standard Deviation 5.5496 |
Primary
Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Red blood cell count on Day 1 at Pre-dose | 3.207 trillion cells per liter | Standard Deviation 0.7733 |
| Part B (Placebo BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Red blood cell count on Day 3 at 12 hours | 3.271 trillion cells per liter | Standard Deviation 0.5725 |
| Part B (Placebo BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Red blood cell count on Follow-up Day 7 | 3.352 trillion cells per liter | Standard Deviation 0.6374 |
| Part B (Placebo BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Reticulocyte count on Day 1 at Pre-dose | 0.025 trillion cells per liter | Standard Deviation 0.0195 |
| Part B (Placebo BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Reticulocyte count on Day 3 at 12 hours | 0.832 trillion cells per liter | Standard Deviation 2.5186 |
| Part B (Placebo BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Reticulocyte count on Follow-up Day 7 | 1.607 trillion cells per liter | Standard Deviation 5.1055 |
| Part B (GSK2586881 BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Reticulocyte count on Day 3 at 12 hours | 3.697 trillion cells per liter | Standard Deviation 12.692 |
| Part B (GSK2586881 BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Red blood cell count on Day 1 at Pre-dose | 2.678 trillion cells per liter | Standard Deviation 0.5117 |
| Part B (GSK2586881 BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Reticulocyte count on Day 1 at Pre-dose | 0.044 trillion cells per liter | — |
| Part B (GSK2586881 BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Red blood cell count on Day 3 at 12 hours | 3.076 trillion cells per liter | Standard Deviation 0.5001 |
| Part B (GSK2586881 BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Reticulocyte count on Follow-up Day 7 | 8.629 trillion cells per liter | Standard Deviation 25.6392 |
| Part B (GSK2586881 BID) | Hematology Parameters Red Blood Cell Count and Reticulocyte Count Assessment Upto Day 7 (Part B) | Red blood cell count on Follow-up Day 7 | 3.314 trillion cells per liter | Standard Deviation 0.77 |
Primary
Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A)
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
Population: The All Subjects - Part A Population was defined as all participants in Part A who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B (Placebo BID) | Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A) | Any AE | 5 Participants |
| Part B (Placebo BID) | Number of Participant With Adverse Event (AE) and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part A) | Anys SAE | 3 Participants |
Primary
Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B)
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
Population: All Subjects - Part B Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B (Placebo BID) | Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) | Any AE | 14 Participant |
| Part B (Placebo BID) | Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) | Any SAE | 4 Participant |
| Part B (GSK2586881 BID) | Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) | Any AE | 15 Participant |
| Part B (GSK2586881 BID) | Number of Par With AE and Serious Adverse Event (SAE) Assessment Upto Day 7 (Part B) | Any SAE | 3 Participant |
Secondary
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A)
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at Pre-dose on Day 1 | NA nano grams per milliliter | — |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 5 minutes on Day 1 | 2854.0 nano grams per milliliter | Standard Deviation 595.47 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 10 minutes on Day 1 | 2692.8 nano grams per milliliter | Standard Deviation 629.78 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 2 hours on Day 1 | 2047.4 nano grams per milliliter | Standard Deviation 497.19 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 6 hours on Day 1 | 5460.0 nano grams per milliliter | Standard Deviation 3213.96 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 10 hours on Day 1 | 10276.6 nano grams per milliliter | Standard Deviation 2641.49 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 12 hours on Day 1 | 8265.4 nano grams per milliliter | Standard Deviation 1905.29 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 0 hours on Day 2 | 3621.6 nano grams per milliliter | Standard Deviation 2654.21 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 1 hour on Day 2 | 17558.6 nano grams per milliliter | Standard Deviation 4359.04 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 12 hours on Day 2 | 7237.8 nano grams per milliliter | Standard Deviation 4281.27 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part A) | GSK2586881 concentration at 24 hours on Day 2 | 3517.8 nano grams per milliliter | Standard Deviation 2433.49 |
Secondary
Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B)
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at Pre-dose on Day 1 | NA nanograms per milliliter | — |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 0.5 hours on Day 1 | 5489.3 nanograms per milliliter | Standard Deviation 1727.81 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 2 hours on Day 1 | 4334.0 nanograms per milliliter | Standard Deviation 1880.42 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 6 hours on Day 1 | 5065.4 nanograms per milliliter | Standard Deviation 8679.92 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 12 hours on Day 1 | 1815.9 nanograms per milliliter | Standard Deviation 809.52 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 0 hours on Day 2 | 2115.3 nanograms per milliliter | Standard Deviation 1164.12 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 0 hours on Day 3 | 2306.6 nanograms per milliliter | Standard Deviation 1356.75 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 0.5 hours on Day 3 | 6810.4 nanograms per milliliter | Standard Deviation 3135.66 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 2 hours on Day 3 | 6060.7 nanograms per milliliter | Standard Deviation 2956.33 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 6 hours on Day 3 | 3808.9 nanograms per milliliter | Standard Deviation 1953.82 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 12 hours on Day 3 | 2416.6 nanograms per milliliter | Standard Deviation 1601.08 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 18 hours on Day 3 | 2701.6 nanograms per milliliter | Standard Deviation 1874.28 |
| Part B (Placebo BID) | Analysis of GSK2586881 Plasma Pharmacokinetic Concentration (Part B) | GSK2586881 concentration at 24 hours on Day 3 | 2254.7 nanograms per milliliter | Standard Deviation 1233.58 |
Secondary
Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A)
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
Population: Pharmacokinetic - Part A Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part B (Placebo BID) | Analysis of Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part A) | 0.384 liters per hour | Standard Error 0.0886 |
Secondary
Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B)
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
Population: Pharmacokinetic - Part B Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part B (Placebo BID) | Analysis Pharmacokinetic Parameter Clearance (CL) for GSK2586881 (Part B) | 0.698 liters per hour | Standard Error 0.0608 |
Secondary
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)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | 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) | CCP-16 at 12 hours | 9.24 nanograms per milliliter |
| Part B (Placebo BID) | 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) | CCP-16 at 24 hours | 9.18 nanograms per milliliter |
| Part B (Placebo BID) | 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) | CCP-16 at 48 hours | 9.91 nanograms per milliliter |
| Part B (Placebo BID) | 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) | CCP-16 at 72 hours | 9.04 nanograms per milliliter |
| Part B (Placebo BID) | 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) | CCP-16 at 120 hours | 8.94 nanograms per milliliter |
| Part B (Placebo BID) | 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) | SP-D at 12 hours | 304.71 nanograms per milliliter |
| Part B (Placebo BID) | 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) | SP-D at 24 hours | 348.51 nanograms per milliliter |
| Part B (Placebo BID) | 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) | SP-D at 48 hours | 307.00 nanograms per milliliter |
| Part B (Placebo BID) | 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) | SP-D at 72 hours | 281.79 nanograms per milliliter |
| Part B (Placebo BID) | 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) | SP-D at 120 hours | 229.94 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | SP-D at 48 hours | 494.70 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CCP-16 at 12 hours | 8.45 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | SP-D at 12 hours | 384.58 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CCP-16 at 24 hours | 9.25 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | SP-D at 120 hours | 350.31 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CCP-16 at 48 hours | 11.04 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | SP-D at 24 hours | 442.35 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CCP-16 at 72 hours | 8.94 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | SP-D at 72 hours | 465.15 nanograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CCP-16 at 120 hours | 7.22 nanograms per milliliter |
Comparison: CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.793495% CI: [0.737, 1.14]Bayesian repeated measures model
Comparison: CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.520595% CI: [0.782, 1.317]Bayesian repeated measures model
Comparison: CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.668295% CI: [0.673, 1.865]Bayesian repeated measures model
Comparison: CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.530495% CI: [0.744, 1.315]Bayesian repeated measures model
Comparison: CCP-16, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.907895% CI: [0.582, 1.112]Bayesian repeated measures model
Comparison: SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.990795% CI: [1.042, 1.526]Bayesian repeated measures model
Comparison: SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.997395% CI: [1.005, 1.606]Bayesian repeated measures model
Comparison: SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.995495% CI: [1.13, 2.331]Bayesian repeated measures model
Comparison: SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.98395% CI: [1.045, 2.588]Bayesian repeated measures model
Comparison: SP-D, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.931295% CI: [0.867, 2.737]Bayesian repeated measures model
Secondary
Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 24 hours | 11.26 milligrams per deciliter |
| Part B (Placebo BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 72 hours | 9.96 milligrams per deciliter |
| Part B (Placebo BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 48 hours | 11.19 milligrams per deciliter |
| Part B (Placebo BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 120 hours | 6.81 milligrams per deciliter |
| Part B (Placebo BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 12 hours | 12.99 milligrams per deciliter |
| Part B (GSK2586881 BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 120 hours | 8.78 milligrams per deciliter |
| Part B (GSK2586881 BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 12 hours | 14.58 milligrams per deciliter |
| Part B (GSK2586881 BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 24 hours | 14.68 milligrams per deciliter |
| Part B (GSK2586881 BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 48 hours | 13.71 milligrams per deciliter |
| Part B (GSK2586881 BID) | Biomarker Analysis for Serum Inflammatory Biomarker C-reactive Protein (CRP) Upto Day 5 (Part B) | CRP at 72 hours | 8.96 milligrams per deciliter |
Comparison: CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.653695% CI: [0.626, 2.024]Bayesian repeated measures model
Comparison: CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.906695% CI: [0.876, 1.955]Bayesian repeated measures model
Comparison: CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.785995% CI: [0.723, 2.066]Bayesian repeated measures model
Comparison: CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.605895% CI: [0.413, 1.963]Bayesian repeated measures model
Comparison: CRP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.692195% CI: [0.456, 3.632]Ratio of Active/Placebo
Secondary
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)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | 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) | CXCL-8 (IL-8) at 24 hours | 17.5 picograms per milliliter |
| Part B (Placebo BID) | 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) | Angiopoietin-2 at 24 hours | 9127.2 picograms per milliliter |
| Part B (Placebo BID) | 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) | Angiopoietin-2 at 48 hours | 9546.3 picograms per milliliter |
| Part B (Placebo BID) | 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) | Angiopoietin-2 at 72 hours | 8859.1 picograms per milliliter |
| Part B (Placebo BID) | 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) | Angiopoietin-2 at 120 hours | 7047.7 picograms per milliliter |
| Part B (Placebo BID) | 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) | Renin at 72 hours | 19.95 picograms per milliliter |
| Part B (Placebo BID) | 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) | Aldosterone at 72 hours | 36.8 picograms per milliliter |
| Part B (Placebo BID) | 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) | CXCL-8 (IL-8) at 48 hours | 22.3 picograms per milliliter |
| Part B (Placebo BID) | 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) | CXCL-8 (IL-8) at 72 hours | 14.5 picograms per milliliter |
| Part B (Placebo BID) | 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) | CXCL-8 (IL-8) at 120 hours | 10.0 picograms per milliliter |
| Part B (Placebo BID) | 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) | IL-6 at 12 hours | 316.2 picograms per milliliter |
| Part B (Placebo BID) | 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) | IL-6 at 24 hours | 317.9 picograms per milliliter |
| Part B (Placebo BID) | 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) | IL-6 at 48 hours | 310.5 picograms per milliliter |
| Part B (Placebo BID) | 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) | IL-6 at 72 hours | 249.9 picograms per milliliter |
| Part B (Placebo BID) | 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) | IL-6 at 120 hours | 142.2 picograms per milliliter |
| Part B (Placebo BID) | 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) | RAGE at 12 hours | 3746 picograms per milliliter |
| Part B (Placebo BID) | 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) | RAGE at 24 hours | 3059 picograms per milliliter |
| Part B (Placebo BID) | 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) | RAGE at 48 hours | 2531 picograms per milliliter |
| Part B (Placebo BID) | 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) | RAGE at 72 hours | 1936 picograms per milliliter |
| Part B (Placebo BID) | 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) | RAGE at 120 hours | 1252 picograms per milliliter |
| Part B (Placebo BID) | 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) | MPO at 12 hours | 60161.0 picograms per milliliter |
| Part B (Placebo BID) | 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) | MPO at 24 hours | 55141.5 picograms per milliliter |
| Part B (Placebo BID) | 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) | MPO at 48 hours | 58717.0 picograms per milliliter |
| Part B (Placebo BID) | 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) | MPO at 72 hours | 42521.0 picograms per milliliter |
| Part B (Placebo BID) | 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) | MPO at 120 hours | 32313.1 picograms per milliliter |
| Part B (Placebo BID) | 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) | CXCL-8 (IL-8) at 12 hours | 18.7 picograms per milliliter |
| Part B (Placebo BID) | 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) | Angiopoietin-2 at 12 hours | 10816.2 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | RAGE at 120 hours | 1292 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Angiopoietin-2 at 12 hours | 8981.1 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CXCL-8 (IL-8) at 24 hours | 16.8 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | IL-6 at 72 hours | 180.7 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Angiopoietin-2 at 24 hours | 8973.9 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | MPO at 120 hours | 47835.2 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Angiopoietin-2 at 48 hours | 9043.3 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | IL-6 at 120 hours | 66.2 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Angiopoietin-2 at 72 hours | 7773.7 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | MPO at 12 hours | 65791.2 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Angiopoietin-2 at 120 hours | 6604.4 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | RAGE at 12 hours | 3461 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Renin at 72 hours | 13.60 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | MPO at 72 hours | 60700.1 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | Aldosterone at 72 hours | 19.5 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | RAGE at 24 hours | 3054 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CXCL-8 (IL-8) at 48 hours | 14.6 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | MPO at 24 hours | 69059.0 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CXCL-8 (IL-8) at 72 hours | 14.1 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | RAGE at 48 hours | 2480 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CXCL-8 (IL-8) at 120 hours | 11.8 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | CXCL-8 (IL-8) at 12 hours | 16.6 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | IL-6 at 12 hours | 313.9 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | RAGE at 72 hours | 1755 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | IL-6 at 24 hours | 231.6 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | MPO at 48 hours | 73790.1 picograms per milliliter |
| Part B (GSK2586881 BID) | 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) | IL-6 at 48 hours | 159.8 picograms per milliliter |
Comparison: CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.0682895% CI: [0.528, 1.501]Bayesian repeated measures model
Comparison: CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.567495% CI: [0.57, 1.609]Bayesian repeated measures model
Comparison: CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.885595% CI: [0.321, 1.316]Bayesian repeated measures model
Comparison: CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.535895% CI: [0.531, 1.76]Bayesian repeated measures model
Comparison: CXCL-8 (IL-8), Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.69995% CI: [0.622, 2.155]Bayesian repeated measures model
Comparison: IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.51395% CI: [0.549, 1.721]Bayesian repeated measures model
Comparison: IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.769695% CI: [0.3, 1.731]Bayesian repeated measures model
Comparison: IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.925495% CI: [0.203, 1.289]Bayesian repeated measures model
Comparison: IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.708895% CI: [0.216, 2.419]Bayesian repeated measures model
Comparison: IL-6, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.878795% CI: [0.112, 1.69]Bayesian repeated measures model
Comparison: RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.733895% CI: [0.714, 1.197]Bayesian repeated measures model
Comparison: RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.495595% CI: [0.703, 1.415]Bayesian repeated measures model
Comparison: RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.526495% CI: [0.541, 1.788]Bayesian repeated measures model
Comparison: RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.618395% CI: [0.454, 1.742]Bayesian repeated measures model
Comparison: RAGE, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.529195% CI: [0.483, 2.118]Bayesian repeated measures model
Comparison: MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.7495% CI: [0.828, 1.448]Bayesian repeated measures model
Comparison: MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.937595% CI: [0.937, 1.683]Bayesian repeated measures model
Comparison: MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.911895% CI: [0.896, 1.771]Bayesian repeated measures model
Comparison: MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.921795% CI: [0.866, 2.382]Bayesian repeated measures model
Comparison: MPO, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.867695% CI: [0.73, 3.064]Bayesian repeated measures model
Comparison: Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.883595% CI: [0.609, 1.135]Bayesian repeated measures model
Comparison: Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.544695% CI: [0.723, 1.33]Bayesian repeated measures model
Comparison: Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.626795% CI: [0.679, 1.333]Bayesian repeated measures model
Comparison: Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.766895% CI: [0.612, 1.26]Bayesian repeated measures model
Comparison: Angiopoietin-2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.6195% CI: [0.588, 1.509]Bayesian repeated measures model
Comparison: Renin, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.815995% CI: [0.291, 1.623]Bayesian repeated measures model
Comparison: Aldosterone, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.798895% CI: [0.106, 2.657]Bayesian repeated measures model
Secondary
Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part B (Placebo BID) | Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) | Total SOFA Score at Day 4 | 7.4 Score on scale |
| Part B (Placebo BID) | Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) | Total SOFA Score at Day 7 | 5.4 Score on scale |
| Part B (GSK2586881 BID) | Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) | Total SOFA Score at Day 4 | 8.0 Score on scale |
| Part B (GSK2586881 BID) | Evaluation of Sequential Organ Failure Assessment (SOFA) Score on Day 4 and Day 7 (Part B) | Total SOFA Score at Day 7 | 6.8 Score on scale |
Secondary
Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B)
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)
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 14, Screening positive Confirmed negative | 1 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 14, Screening positive and Confirmed positive | 0 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 14, Screening negative | 8 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 28, Screening positive Confirmed negative | 0 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 28, Screening positive and Confirmed positive | NA Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 28, Screening negative | 10 Participants |
| Part B (GSK2586881 BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 28, Screening positive and Confirmed positive | NA Participants |
| Part B (GSK2586881 BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 14, Screening positive Confirmed negative | 0 Participants |
| Part B (GSK2586881 BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 28, Screening positive Confirmed negative | 0 Participants |
| Part B (GSK2586881 BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 14, Screening positive and Confirmed positive | NA Participants |
| Part B (GSK2586881 BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 28, Screening negative | 11 Participants |
| Part B (GSK2586881 BID) | Immunogenicity Assessment With Respect to Anti-ACE2 Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part B) | Day 14, Screening negative | 13 Participants |
Secondary
Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A)
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)
Population: The All Subjects - Part A Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) | Row 6, Screening negative | 1 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) | Day 14, Screening positive Confirmed negative | 1 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) | Day 14, Screening positive and Confirmed positive | 0 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) | Day 14, Screening negative | 1 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) | Day 28, Screening positive Confirmed negative | 0 Participants |
| Part B (Placebo BID) | Immunogenicity Assessment With Respect to Anti-Acetychollinesterase2 (ACE2) Binding Antibodies at Follow-up Day 14 and Follow-up Day 28 (Part A) | Day 28, Screening positive and Confirmed positive | NA Participants |
Secondary
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)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 26 hours | 182.9 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 52 hours | 183.9 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 0.5 hours | 166.2 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 32 hours | 174.2 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 30 hours | 169.5 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 1 hour | 178.1 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 24.5 hours | 189.3 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 2 hours | 181.5 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 36 hours | 200.5 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 4 hours | 182.8 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 28 hours | 191.1 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 6 hours | 173.2 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 42 hours | 172.7 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 8 hours | 160.9 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 66 hours | 154.6 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 24 hours | 183.5 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 72 hours | 150.4 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 48 hours | 169.9 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 168 hours | 198.9 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 25 hours | 179.6 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 48.5 hours | 195.8 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 12 hours | 173.7 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 54 hours | 191.6 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 18 hours | 180.5 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 56 hours | 181.6 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 49 hours | 166.5 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 60 hours | 170.8 Ratio |
| Part B (Placebo BID) | 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) | PaO2/FiO2 at 50 hours | 168.3 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 60 hours | 162.4 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 18 hours | 176.8 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 24 hours | 167.3 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 24.5 hours | 175.8 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 25 hours | 167.1 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 26 hours | 183.2 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 28 hours | 167.9 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 52 hours | 168.4 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 49 hours | 175.1 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 30 hours | 169.3 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 32 hours | 155.3 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 36 hours | 159.5 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 42 hours | 171.0 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 48 hours | 178.2 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 48.5 hours | 175.5 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 50 hours | 167.5 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 0.5 hours | 173.7 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 1 hour | 160.2 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 2 hours | 162.3 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 4 hours | 155.1 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 6 hours | 156.7 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 66 hours | 162.6 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 72 hours | 153.3 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 168 hours | 168.9 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 8 hours | 170.6 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 54 hours | 172.1 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 56 hours | 173.9 Ratio |
| Part B (GSK2586881 BID) | 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) | PaO2/FiO2 at 12 hours | 179.6 Ratio |
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 0.646895% CI: [0.765, 1.321]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hourp-value: 0.196595% CI: [0.658, 1.136]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 0.168195% CI: [0.694, 1.129]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hoursp-value: 0.087795% CI: [0.669, 1.075]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 0.201195% CI: [0.715, 1.159]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hoursp-value: 0.685595% CI: [0.842, 1.345]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.609395% CI: [0.8, 1.325]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hoursp-value: 0.43595% CI: [0.765, 1.253]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.223295% CI: [0.722, 1.195]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hoursp-value: 0.271695% CI: [0.733, 1.2]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hoursp-value: 0.286695% CI: [0.726, 1.19]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hoursp-value: 0.503395% CI: [0.78, 1.27]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hoursp-value: 0.149395% CI: [0.684, 1.12]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hoursp-value: 0.494795% CI: [0.759, 1.301]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hoursp-value: 0.195195% CI: [0.678, 1.161]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hoursp-value: 0.051295% CI: [0.612, 1.05]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hoursp-value: 0.4795% CI: [0.775, 1.279]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.63495% CI: [0.811, 1.368]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.212995% CI: [0.689, 1.183]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hoursp-value: 0.641895% CI: [0.798, 1.411]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.479795% CI: [0.754, 1.315]Ratio of Active/Placebo
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hoursp-value: 0.265995% CI: [0.703, 1.199]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.210295% CI: [0.687, 1.159]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hoursp-value: 0.362395% CI: [0.74, 1.24]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.349995% CI: [0.73, 1.225]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.649495% CI: [0.787, 1.377]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.556795% CI: [0.766, 1.358]Bayesian repeated measures model
Comparison: PaO2/FiO2, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hoursp-value: 0.109595% CI: [0.615, 1.073]Bayesian repeated measures model
Secondary
Measure of Oxygenation Index Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 32 hours | 9.7 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 6 hours | 10.2 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 36 hours | 8.7 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 24 hours | 10.6 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 42 hours | 9.4 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 1 hour | 9.0 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 48 hours | 10.2 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 24.5 hours | 9.0 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 48.5 hours | 9.2 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 8 hours | 10.4 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 49 hours | 10.8 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 25 hours | 8.9 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 50 hours | 10.4 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 4 hours | 9.3 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 52 hours | 9.8 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 26 hours | 9.2 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 54 hours | 9.4 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 12 hours | 9.3 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 56 hours | 9.3 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 28 hours | 9.0 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 60 hours | 8.9 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 2 hours | 9.9 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 66 hours | 10.5 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 30 hours | 9.8 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 72 hours | 10.5 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 18 hours | 8.7 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 168 hours | 5.8 Percentage |
| Part B (Placebo BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 0.5 hours | 10.0 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 168 hours | 6.4 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 0.5 hours | 10.6 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 1 hour | 12.2 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 2 hours | 11.0 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 4 hours | 11.6 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 6 hours | 12.3 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 8 hours | 12.4 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 12 hours | 11.0 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 18 hours | 10.8 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 24 hours | 10.6 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 24.5 hours | 9.6 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 25 hours | 10.5 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 26 hours | 8.3 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 28 hours | 9.4 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 30 hours | 9.6 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 32 hours | 10.4 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 36 hours | 10.1 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 42 hours | 10.2 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 48 hours | 8.8 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 48.5 hours | 8.4 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 49 hours | 8.9 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 50 hours | 9.2 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 52 hours | 9.4 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 54 hours | 9.7 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 56 hours | 8.5 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 60 hours | 9.9 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 66 hours | 8.2 Percentage |
| Part B (GSK2586881 BID) | Measure of Oxygenation Index Upto Day 7 (Part B) | Oxygenation index at 72 hours | 9.7 Percentage |
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 0.609895% CI: [0.721, 1.644]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hourp-value: 0.944195% CI: [0.931, 2.068]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 0.717395% CI: [0.749, 1.621]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hoursp-value: 0.829295% CI: [0.81, 1.949]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 0.800895% CI: [0.775, 1.832]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hoursp-value: 0.790595% CI: [0.776, 1.799]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.756695% CI: [0.737, 1.958]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hoursp-value: 0.834995% CI: [0.812, 2.05]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.473995% CI: [0.713, 1.527]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hoursp-value: 0.629195% CI: [0.763, 1.647]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hoursp-value: 0.803295% CI: [0.83, 1.814]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hoursp-value: 0.32595% CI: [0.626, 1.416]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hoursp-value: 0.582895% CI: [0.687, 1.63]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hoursp-value: 0.454695% CI: [0.661, 1.512]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hoursp-value: 0.615895% CI: [0.719, 1.639]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hoursp-value: 0.774895% CI: [0.752, 1.77]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hoursp-value: 0.656595% CI: [0.686, 1.714]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.277395% CI: [0.566, 1.38]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.360695% CI: [0.61, 1.467]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hoursp-value: 0.221195% CI: [0.555, 1.317]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.28695% CI: [0.587, 1.348]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hoursp-value: 0.407995% CI: [0.609, 1.51]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.528495% CI: [0.614, 1.663]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hoursp-value: 0.358695% CI: [0.568, 1.458]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.676895% CI: [0.672, 1.853]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.157495% CI: [0.488, 1.39]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.3995% CI: [0.521, 1.584]Bayesian repeated measures model
Comparison: Oxygenation index, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hoursp-value: 0.591595% CI: [0.748, 1.516]Bayesian repeated measures model
Secondary
Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B)
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
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 56 hours | 25.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 66 hours | 24.5 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 72 hours | 21.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 168 hours | 15.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 49 hours | 26.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 50 hours | 24.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 52 hours | 26.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 52 hours | 23.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 54 hours | 23.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 26 hours | 23.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 28 hours | 23.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 30 hours | 23.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 32 hours | 23.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 36 hours | 23.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 50 hours | 22.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 0.5 hours | 24.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 1 hour | 24.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 2 hours | 23.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 4 hours | 24.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 6 hours | 24.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 54 hours | 25.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 60 hours | 22.5 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 60 hours | 24.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 66 hours | 24.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 72 hours | 22.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 168 hours | 19.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 1 hour | 9.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 2 hours | 9.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 28 hours | 9.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 30 hours | 9.5 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 8 hours | 9.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 12 hours | 9.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 18 hours | 10.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 24 hours | 9.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 24.5 hours | 9.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 25 hours | 9.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 26 hours | 9.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 4 hours | 9.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 6 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 32 hours | 9.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 36 hours | 9.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 42 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 52 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 54 hours | 9.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 56 hours | 9.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 60 hours | 8.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 66 hours | 9.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 72 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 168 hours | 6.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 0.5 hours | 29.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 4 hours | 28.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 6 hours | 28.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 8 hours | 28.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 12 hours | 28.5 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 18 hours | 29.5 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 24 hours | 28.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 24.5 hours | 29.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 25 hours | 29.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 1 hour | 28.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 2 hours | 27.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 26 hours | 27.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 28 hours | 29.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 30 hours | 29.5 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 32 hours | 30.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 36 hours | 30.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 42 hours | 28.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 48 hours | 25.7 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 48.5 hours | 26.0 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 8 hours | 25.9 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 42 hours | 24.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 48 hours | 23.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 48.5 hours | 23.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 49 hours | 22.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 56 hours | 23.2 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 12 hours | 24.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 18 hours | 25.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 24 hours | 24.1 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 24.5 hours | 23.8 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 25 hours | 24.4 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 0.5 hours | 10.3 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 50 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 48 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 48.5 hours | 9.6 centimeters of water pressure |
| Part B (Placebo BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 49 hours | 9.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 50 hours | 8.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 60 hours | 23.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 30 hours | 28.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 66 hours | 23.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 52 hours | 8.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 72 hours | 25.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 48 hours | 8.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 48.5 hours | 28.1 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 54 hours | 8.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 49 hours | 28.1 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 32 hours | 28.1 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 50 hours | 27.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 56 hours | 8.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 52 hours | 26.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 50 hours | 25.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 8 hours | 21.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 52 hours | 25.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 60 hours | 8.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 54 hours | 23.1 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 36 hours | 27.0 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 26 hours | 23.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 66 hours | 9.1 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 28 hours | 23.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 25 hours | 22.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 30 hours | 23.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 72 hours | 8.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 32 hours | 23.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 42 hours | 27.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 168 hours | 7.5 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 56 hours | 22.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 12 hours | 24.0 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 0.5 hours | 25.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 0.5 hours | 29.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 1 hour | 24.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 2 hours | 29.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 2 hours | 24.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 48 hours | 26.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 4 hours | 24.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 4 hours | 28.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 168 hours | 17.0 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 48.5 hours | 8.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 54 hours | 27.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 6 hours | 29.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 56 hours | 27.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 6 hours | 25.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 60 hours | 26.8 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 8 hours | 29.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 66 hours | 25.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 18 hours | 21.5 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 72 hours | 29.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 12 hours | 29.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 168 hours | 25.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 0.5 hours | 9.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 36 hours | 23.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 1 hour | 9.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 18 hours | 28.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 42 hours | 8.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 28 hours | 9.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 24 hours | 28.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 30 hours | 9.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 42 hours | 23.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 8 hours | 9.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 24.5 hours | 28.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 12 hours | 9.5 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 24 hours | 24.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 18 hours | 9.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 48 hours | 23.1 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 24 hours | 9.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 1 hour | 30.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 24.5 hours | 9.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 49 hours | 8.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 25 hours | 8.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 48.5 hours | 25.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 26 hours | 9.3 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 2 hours | 9.7 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 25 hours | 27.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 4 hours | 9.6 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 24.5 hours | 23.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 6 hours | 9.5 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 32 hours | 9.2 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 26 hours | 27.4 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Peak ventilatory pressure at 28 hours | 26.9 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | PEEP at 36 hours | 9.0 centimeters of water pressure |
| Part B (GSK2586881 BID) | Measures of Oxygenation Including Level of Positive End Expiratory Pressure (PEEP), Peak Ventilatory Pressures and Plateau Ventilatory Pressures Upto Day 7 (Part B) | Plateau ventilatory pressure at 49 hours | 24.6 centimeters of water pressure |
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 0.259895% CI: [0.752, 1.215]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hourp-value: 0.394995% CI: [0.783, 1.273]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 0.417595% CI: [0.791, 1.294]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hoursp-value: 0.44295% CI: [0.806, 1.292]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 0.443295% CI: [0.811, 1.262]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hoursp-value: 0.457895% CI: [0.818, 1.229]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.336595% CI: [0.79, 1.167]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hoursp-value: 0.333995% CI: [0.77, 1.163]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.360895% CI: [0.786, 1.166]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hoursp-value: 0.358495% CI: [0.788, 1.168]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hoursp-value: 0.121995% CI: [0.725, 1.073]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hoursp-value: 0.466295% CI: [0.814, 1.21]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hoursp-value: 0.574895% CI: [0.828, 1.247]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hoursp-value: 0.410495% CI: [0.786, 1.204]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hoursp-value: 0.511495% CI: [0.817, 1.246]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hoursp-value: 0.421395% CI: [0.783, 1.2]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hoursp-value: 0.266395% CI: [0.731, 1.132]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.237395% CI: [0.72, 1.142]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.257595% CI: [0.721, 1.149]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hoursp-value: 0.217395% CI: [0.708, 1.127]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.240695% CI: [0.717, 1.143]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hoursp-value: 0.247195% CI: [0.721, 1.151]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.258595% CI: [0.727, 1.157]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hoursp-value: 0.310195% CI: [0.737, 1.17]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.247695% CI: [0.727, 1.16]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.388795% CI: [0.767, 1.222]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.229495% CI: [0.749, 1.146]Bayesian repeated measures model
Comparison: PEEP, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hoursp-value: 0.852295% CI: [0.916, 1.234]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 0.588595% CI: [0.89, 1.164]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hourp-value: 0.855895% CI: [0.94, 1.23]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hourp-value: 0.837495% CI: [0.932, 1.224]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hoursp-value: 0.588695% CI: [0.887, 1.152]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 0.753295% CI: [0.918, 1.18]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hoursp-value: 0.710895% CI: [0.906, 1.179]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.744595% CI: [0.918, 1.19]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hoursp-value: 0.375995% CI: [0.863, 1.115]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.39895% CI: [0.859, 1.118]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hoursp-value: 0.323195% CI: [0.849, 1.103]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hoursp-value: 0.124595% CI: [0.812, 1.056]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hoursp-value: 0.463195% CI: [0.87, 1.134]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hoursp-value: 0.102695% CI: [0.801, 1.047]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hoursp-value: 0.315295% CI: [0.85, 1.101]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hoursp-value: 0.076295% CI: [0.803, 1.035]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hoursp-value: 0.027495% CI: [0.763, 1.003]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hoursp-value: 0.359495% CI: [0.853, 1.112]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.702795% CI: [0.906, 1.197]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.866195% CI: [0.941, 1.246]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hoursp-value: 0.808495% CI: [0.924, 1.228]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.950495% CI: [0.976, 1.3]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hoursp-value: 0.5395% CI: [0.871, 1.164]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.859595% CI: [0.942, 1.243]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hoursp-value: 0.880295% CI: [0.943, 1.261]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.923295% CI: [0.958, 1.278]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.791195% CI: [0.902, 1.256]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.994695% CI: [1.059, 1.514]Bayesian repeated measures model
Comparison: Peak ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hoursp-value: 0.98395% CI: [1.019, 1.444]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 0.802495% CI: [0.91, 1.261]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 1 hourp-value: 0.480695% CI: [0.843, 1.166]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 0.665895% CI: [0.869, 1.223]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 4 hoursp-value: 0.613195% CI: [0.856, 1.212]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 0.579595% CI: [0.856, 1.197]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 8 hoursp-value: 0.020995% CI: [0.716, 0.993]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.482395% CI: [0.83, 1.187]Mixed Models Analysis
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 18 hoursp-value: 0.040695% CI: [0.703, 1.021]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.518695% CI: [0.844, 1.169]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24.5 hoursp-value: 0.38795% CI: [0.824, 1.132]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 25 hoursp-value: 0.128195% CI: [0.77, 1.065]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 26 hoursp-value: 0.475495% CI: [0.837, 1.181]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 28 hoursp-value: 0.562795% CI: [0.856, 1.217]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 30 hoursp-value: 0.555295% CI: [0.848, 1.22]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 32 hoursp-value: 0.50395% CI: [0.843, 1.201]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 36 hoursp-value: 0.555895% CI: [0.84, 1.218]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 42 hoursp-value: 0.270995% CI: [0.769, 1.135]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.414395% CI: [0.795, 1.208]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.788695% CI: [0.891, 1.348]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 49 hoursp-value: 0.760795% CI: [0.885, 1.353]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.867795% CI: [0.922, 1.4]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 52 hoursp-value: 0.701295% CI: [0.847, 1.302]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.515695% CI: [0.805, 1.23]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 56 hoursp-value: 0.352495% CI: [0.783, 1.178]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.63895% CI: [0.845, 1.292]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.400395% CI: [0.743, 1.241]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.881795% CI: [0.907, 1.502]Bayesian repeated measures model
Comparison: Plateau ventilatory pressure, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 168 hoursp-value: 0.814595% CI: [0.804, 1.505]Bayesian repeated measures model
Secondary
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)
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
Population: The All Subjects - Part B Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B (Placebo BID) | 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) | Rifle score GFR, I to I | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, Fo to I | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, NAKI to NAKI | 10 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, NAKI to R | 1 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, NAKI to Fo | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score GFR, MISS | 15 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, NAKI to R | 2 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, I to NAKI | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, NAKI to I | 2 Participants |
| Part B (Placebo BID) | 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) | Rifle score GFR, NAKI to NAKI | 5 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, R to NAKI | 1 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, NAKI to NAKI | 3 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, I to NAKI | 3 Participants |
| Part B (Placebo BID) | 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) | Rifle score GFR, R to I | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, I to R | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, I to I | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, Fo to NAKI | 1 Participants |
| Part B (Placebo BID) | 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) | Rifle score GFR, I to NAKI | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, Fo to R | 0 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, R to NAKI | 1 Participants |
| Part B (Placebo BID) | 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) | Rifle score urine, Fo to Fo | 1 Participants |
| Part B (Placebo BID) | 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) | Rifle score total, MISS | 15 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, Fo to Fo | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, MISS | 14 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, NAKI to NAKI | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, NAKI to R | 0 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, R to NAKI | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, I to NAKI | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, I to I | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score total, Fo to I | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score GFR, MISS | 14 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score GFR, NAKI to NAKI | 2 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score GFR, R to I | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score GFR, I to NAKI | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score GFR, I to I | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, NAKI to NAKI | 11 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, NAKI to Fo | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, NAKI to R | 0 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, NAKI to I | 0 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, R to NAKI | 2 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, I to NAKI | 2 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, I to R | 1 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, Fo to NAKI | 0 Participants |
| Part B (GSK2586881 BID) | 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) | Rifle score urine, Fo to R | 1 Participants |
Secondary
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)
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.
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 48.5 hours | 2.90 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 0.5 hours | 3.10 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 2 hours | 2.52 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 6 hours | 2.63 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 12 hours | 2.50 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 24 hours | 2.11 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 48 hours | 1.61 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 48.5 hours | 2.18 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 50 hours | 1.51 Ratio |
| Part B (Placebo BID) | 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) | Row 23Ang II/Ang1-7 at 54 hours | 1.64 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 60 hours | 1.55 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 66 hours | 1.81 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 72 hours | 1.75 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 96 hours | 2.02 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-7 at 120 hours | 1.66 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 0.5 hours | 4.35 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 2 hours | 3.82 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 6 hours | 3.20 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 12 hours | 2.90 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 24 hours | 2.35 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 48 hours | 2.68 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 50 hours | 2.11 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 54 hours | 2.21 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 60 hours | 2.52 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 66 hours | 2.90 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 72 hours | 2.91 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 96 hours | 1.72 Ratio |
| Part B (Placebo BID) | 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) | Ang II/Ang1-5 at 120 hours | 1.93 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 120 hours | 0.64 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 72 hours | 0.76 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 0.5 hours | 0.19 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 0.5 hours | 0.29 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 2 hours | 0.24 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 50 hours | 0.53 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 6 hours | 0.20 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 2 hours | 0.38 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 12 hours | 0.49 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 66 hours | 0.64 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 24 hours | 0.37 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 6 hours | 0.36 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 48 hours | 0.65 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 54 hours | 0.68 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 48.5 hours | 0.51 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 12 hours | 0.72 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 50 hours | 0.42 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 96 hours | 1.41 Ratio |
| Part B (GSK2586881 BID) | 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) | Row 23Ang II/Ang1-7 at 54 hours | 0.40 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 24 hours | 0.68 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 60 hours | 0.48 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 60 hours | 0.86 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 66 hours | 0.45 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 48 hours | 0.85 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 72 hours | 0.42 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 120 hours | 1.53 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-7 at 96 hours | 0.69 Ratio |
| Part B (GSK2586881 BID) | 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) | Ang II/Ang1-5 at 48.5 hours | 0.56 Ratio |
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 195% CI: [0.032, 0.14]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 195% CI: [0.048, 0.209]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 195% CI: [0.054, 0.243]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.999695% CI: [0.113, 0.547]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.999195% CI: [0.13, 0.634]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.997995% CI: [0.149, 0.682]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 195% CI: [0.091, 0.417]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.999895% CI: [0.119, 0.539]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.998595% CI: [0.141, 0.666]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.997795% CI: [0.162, 0.73]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.999995% CI: [0.105, 0.468]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.999695% CI: [0.119, 0.57]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hoursp-value: 0.662195% CI: [0.319, 2.136]Bayesian repeated measures model
Comparison: Ang II/Ang1-5, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.708595% CI: [0.324, 1.847]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 195% CI: [0.028, 0.14]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 195% CI: [0.043, 0.216]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 195% CI: [0.034, 0.177]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.999895% CI: [0.086, 0.453]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.999995% CI: [0.075, 0.4]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.986395% CI: [0.173, 0.901]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.999895% CI: [0.103, 0.529]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.999295% CI: [0.119, 0.626]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.999595% CI: [0.102, 0.561]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.996495% CI: [0.131, 0.729]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.999595% CI: [0.107, 0.584]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.999395% CI: [0.098, 0.578]Ratio of Active/Placebo
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hoursp-value: 0.978195% CI: [0.119, 0.969]Bayesian repeated measures model
Comparison: Ang II/Ang1-7, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.937595% CI: [0.154, 1.341]Bayesian repeated measures model
Secondary
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B)
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.
Population: The All Subjects - Part B Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 66 hours | 7.33 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 2 hours | 12.05 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 6 hours | 11.00 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 12 hours | 10.90 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 24 hours | 8.35 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 48 hours | 8.10 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 48.5 hours | 8.63 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 50 hours | 6.82 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 54 hours | 7.03 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 60 hours | 7.02 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 0.5 hours | 14.14 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 72 hours | 6.62 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 96 hours | 4.72 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 120 hours | 5.21 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 0.5 hours | 2.17 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 2 hours | 2.18 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 6 hours | 2.34 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 12 hours | 2.78 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 24 hours | 2.38 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 48 hours | 2.39 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 48.5 hours | 2.30 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 50 hours | 2.53 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 54 hours | 2.52 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 60 hours | 2.26 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 66 hours | 2.19 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 72 hours | 1.72 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 96 hours | 2.23 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 120 hours | 2.19 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 0.5 hours | 3.12 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 2 hours | 3.29 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 6 hours | 2.92 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 12 hours | 3.03 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 24 hours | 2.87 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 48 hours | 3.58 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 48.5 hours | 2.77 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 50 hours | 3.20 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 54 hours | 3.16 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 60 hours | 3.57 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 66 hours | 3.40 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 72 hours | 2.66 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 96 hours | 1.77 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 120 hours | 2.38 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 12 hours | 6.82 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 0.5 hours | 2.44 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 50 hours | 4.91 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 2 hours | 2.80 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 72 hours | 4.70 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 6 hours | 2.89 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 54 hours | 3.21 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 12 hours | 3.33 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 24 hours | 6.25 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 24 hours | 2.41 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 60 hours | 2.78 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 48 hours | 3.74 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 60 hours | 4.74 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 48.5 hours | 2.89 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 66 hours | 2.71 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 50 hours | 2.58 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 48 hours | 5.71 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 54 hours | 2.32 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 72 hours | 2.50 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 60 hours | 2.38 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 120 hours | 3.21 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 66 hours | 1.84 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 96 hours | 1.28 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 72 hours | 1.93 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 48.5 hours | 5.54 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 96 hours | 1.70 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 120 hours | 1.38 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | AngII at 120 hours | 2.64 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 66 hours | 3.97 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 0.5 hours | 8.58 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 0.5 hours | 13.15 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 2 hours | 7.50 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 50 hours | 6.13 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 6 hours | 8.38 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 2 hours | 12.05 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 12 hours | 5.07 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 96 hours | 2.43 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 24 hours | 3.57 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 6 hours | 15.33 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 48 hours | 4.59 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-7 at 54 hours | 5.78 picograms per milliliter |
| Part B (GSK2586881 BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II, Ang (1-7) and Ang (1-5) Upto Day 5(Part B) | Ang1-5 at 48.5 hours | 5.26 picograms per milliliter |
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.999995% CI: [0.114, 0.532]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 195% CI: [0.083, 0.359]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 0.999995% CI: [0.111, 0.492]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 0.999795% CI: [0.121, 0.568]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.999795% CI: [0.136, 0.66]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.999195% CI: [0.133, 0.632]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.963195% CI: [0.213, 1.081]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.994195% CI: [0.157, 0.789]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.987595% CI: [0.179, 0.891]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.995695% CI: [0.151, 0.759]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.996495% CI: [0.157, 0.747]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.999195% CI: [0.13, 0.647]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hoursp-value: 0.98520.9852% CI: [0.137, 0.906]Bayesian repeated measures model
Comparison: AngII, Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.971995% CI: [0.23, 1.014]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 195% CI: [2.263, 6.919]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 195% CI: [1.976, 6.052]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 195% CI: [2.06, 6.345]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.980695% CI: [1.031, 3.17]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.912995% CI: [0.828, 2.636]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.989195% CI: [1.098, 3.349]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.998395% CI: [1.316, 3.974]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.9995% CI: [1.112, 3.359]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.799695% CI: [0.729, 2.163]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.777895% CI: [0.718, 2.087]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.77395% CI: [0.705, 2.113]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.895195% CI: [0.814, 2.604]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hoursp-value: 0.932495% CI: [0.276, 1.183]Bayesian repeated measures model
Comparison: Ang1-5 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.898295% CI: [0.351, 1.257]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 0.5 hoursp-value: 0.999895% CI: [1.91, 8.905]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 2 hoursp-value: 0.999395% CI: [1.689, 7.97]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 6 hoursp-value: 195% CI: [2.392, 11.754]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 12 hoursp-value: 0.971395% CI: [0.972, 5.136]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 24 hoursp-value: 0.964995% CI: [0.94, 4.975]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48 hoursp-value: 0.874995% CI: [0.711, 3.473]Mixed Models Analysis
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 48.5 hoursp-value: 0.956695% CI: [0.899, 4.342]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 50 hoursp-value: 0.954995% CI: [0.862, 4.173]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 54 hoursp-value: 0.927595% CI: [0.816, 4.005]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 60 hoursp-value: 0.748395% CI: [0.584, 3.007]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 66 hoursp-value: 0.64895% CI: [0.516, 2.675]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 72 hoursp-value: 0.903895% CI: [0.741, 4.17]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 96 hoursp-value: 0.733995% CI: [0.49, 3.915]Bayesian repeated measures model
Comparison: Ang1-7 , Part B (Placebo BID) Vs Part B (GSK2586881 BID) at 120 hoursp-value: 0.771495% CI: [0.651, 3.321]Bayesian repeated measures model
Secondary
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A)
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).
Population: All Subjects - Part A Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 24 hours on Day 2 | 0.290 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at Pre-dose on Day 1 | 6.167 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 5 minutes on Day 1 | 0.268 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 10 minutes on Day 1 | 0.241 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 2 hours on Day 1 | 0.210 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 6 hours on Day 1 | 0.190 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 10 hours on Day 1 | 0.118 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 12 hours on Day 1 | 0.221 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 0 hours on Day 2 | 0.182 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 1 hour on Day 2 | 0.206 Ratio |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Ang II/ Ang (1-7) Upto Day 2 (Part A) | AngII/ Ang1-7 at 12 hours on Day 2 | 0.094 Ratio |
Secondary
Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A)
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).
Population: All Subjects - Part A Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 6 hours on Day 1 | 4.3 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 10 hours on Day 1 | 2.0 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 12 hours on Day 1 | 3.3 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 0 hours on Day 2 | 1.7 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 1 hour on Day 2 | 4.3 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 12 hours on Day 2 | 1.8 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 24 hours on Day 2 | 1.5 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at Pre-dose on Day 1 | 4.3 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 5 minutes on Day 1 | 28.7 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 10 minutes on Day 1 | 25.7 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 2 hours on Day 1 | 18.7 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 6 hours on Day 1 | 22.8 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 10 hours on Day 1 | 16.8 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 12 hours on Day 1 | 15.1 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 0 hours on Day 2 | 9.1 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 1 hour on Day 2 | 20.9 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 12 hours on Day 2 | 18.8 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | Ang1-7 at 24 hours on Day 2 | 5.2 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at Pre-dose on Day 1 | 26.5 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 5 minutes on Day 1 | 7.7 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 10 minutes on Day 1 | 6.2 picograms per milliliter |
| Part B (Placebo BID) | Pharmacodynamic/Biomarker Analysis (Renin-angiotensin System Cascade Biomarkers) to Include Angiotensin (Ang) II and Ang (1-7) Upto Day 2 (Part A) | AngII at 2 hours on Day 1 | 3.9 picograms per milliliter |