SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDS

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00996840

Collaborator

(none)

Enrollment

Locations

Arms

39.8

Actual Duration (Months)

12.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an early phase (Phase IIa), randomized, double-blind, parallel group, multi-centre study for subjects with trauma (physical injury) who are at risk for developing Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). The primary purpose of the study is to evaluate the safety and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha (MAPK) (prevents inflammation of tissue), in comparison to a placebo.

Condition or Disease	Intervention/Treatment	Phase
Lung Injury, Acute	Drug: SB-681323 Intravenous 3mg Drug: SB-681323 Intravenous 7.5 mg Drug: SB-681323 Intravenous 7.5mg Drug: SB-681323 Intravenous 10mg Other: Placebo	Phase 2

Detailed Description

The acute respiratory distress syndrome (ARDS) is a form of severe 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 and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha mitogen-activated protein kinase.

The rationale behind the development of this drug is that there are elevated levels of circulating pro-inflammatory agents, such as cytokines which are biological agents that increase levels of inflammation in the lungs. These agents are part of an 'inflammatory loop' and it may be beneficial to the condition to dampen this loop.

p38 mitogen activated protein kinase (MAPK) plays a major role in the regulation and activation of intracellular proteins which are subsequently involved in the regulation of the cytokines. The pathway is activated by 'stress', such as injury, causing the inflammation. Therefore, 'dampening' this system should reduce the level of inflammation.

This study will investigate the anti-inflammatory activity, efficacy (effectiveness at achieving the desired effect) and safety of SB-681323.

To measure the efficacy of the drug, biomarkers will be measured. Biomarkers are biological agents in the body that are effected by the presence of specific injury or inflammation and are directly or indirectly linked to a regulatory system of event in the body. They are used to measure for the presence and severity of the condition in question. This study will investigate biomarkers linked directly or indirectly to the p38 alpha regulatory mechanism/system. We will be measuring biomarkers such as serum inflammatory biomarkers, coagulation (blood clotting) system biomarkers, biomarkers of endothelial cell / neutrophil interaction and biomarkers of lung epithelial cell injury.

Study Design

Study Type:

Interventional

Actual Enrollment :

77 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Assessment of the Anti-Inflammatory Activity, Efficacy and Safety of Intravenous SB-681323 in Subjects at Risk for Development of Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS).

Actual Study Start Date :

Oct 16, 2009

Actual Primary Completion Date :

Feb 9, 2013

Actual Study Completion Date :

Feb 9, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 - SB-681323 Intravenous 3mg 3mg SB-681323 Intravenous administration, infused over 4 hours	Drug: SB-681323 Intravenous 3mg 3 mg SB-681323 Intravenous administration infused over 4 hours
Experimental: Cohort 2 - SB-681323 Intravenous 7.5 mg 7.5 mg SB-681323 Intravenous administration infused over 24 hours	Drug: SB-681323 Intravenous 7.5 mg 7.5 mg SB-681323 Intravenous administration infused over 24 hours
Experimental: Cohort 3 - SB-681323 Intravenous 7.5mg 7.5 mg SB-681323 Intravenous administration infused over 4 hours	Drug: SB-681323 Intravenous 7.5mg 7.5 mg SB-681323 Intravenous administration infused over 4 hours
Experimental: Cohort 4 - SB-681323 Intravenous 10mg 10 mg SB-681323 Intravenous administration infused over 24 hours	Drug: SB-681323 Intravenous 10mg 10 mg SB-681323 Intravenous administration infused over 24 hours
Experimental: Combined Placebo Placebo to match intervention	Other: Placebo Placebo to match intervention

Outcome Measures

Primary Outcome Measures

Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Mean hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, white blood cell count were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Hematology Parameters- Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Mean hematology parameters including hemoglobin, MCHC were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Hematology Parameters- Mean Corpuscle Hemoglobin ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Hematology parameter mean corpuscle hemoglobin was reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Hematology Parameters-Mean Corpuscle Volume ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Absolute values of mean corpuscle volume were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Hematology Parameters-reticulocytes, Red Blood Cell Count ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Absolute values of reticulocytes and red blood cell count were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Clinical Chemistry Parameters- Albumin and Total Protein ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Absolute values of albumin and total protein were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Clinical Chemistry Parameters-alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Absolute values of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and gamma glutamyl transferase were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Clinical Chemistry Parameters- Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Absolute values of direct bilirubin, total bilirubin, creatinine and uric acid were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Clinical Chemistry Parameters- Calcium, Chloride, Glucose, Bicarbonate, Potassium, Sodium and Ratio of Urea to Blood Urea Nitrogen (Urea/BUN) ["Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"]
Absolute values of calcium, chloride, glucose, bicarbonate, potassium, sodium and Urea/BUN were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Clinical Chemistry Parameters-estradiol [Day 1 (pre-dose) and Day 3 (24 h)]
Absolute values of Estradiol were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Mean Clinical Chemistry Parameters-Blood pH at Screening [Screening]
Absolute values of Blood pH at screening were reported as clinical chemistry parameter.
Vital Parameter- Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"]
Absolute values of SBP and DBP were reported.
Vital Parameter: Mean Heart Rate [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"]
Absolute values of mean heart rate were reported.
Vital Sign: Mean Percent Oxygen (O2) in Blood [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"]
Absolute values of mean percent O2 in blood were reported.
Vital Signs: Mean Oxygen Saturation (SaO2) Via Pulse Oximetry [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"]
Assessment of SaO2 via pulse oximetry was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Vital Signs: Mean Level of Positive End Expiratory Pressure [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"]
Assessment of level of positive end expiratory pressure was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Vital Signs: Mean Level of Peak and Plateau Ventilator Pressures [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"]
Assessment of mean level of peak and plateau ventilator pressures was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Vital Signs: Mean Oxygen Requirement (FiO2) Via Pulse Oximetry [For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"]
Assessment of mean FiO2 via pulse oximetry was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Mean Electrocardiogram (ECG) Parameters Including PR, QRS, QT, and QTcB, QTcF, RR Intervals [Day 2, pre-dose, Day 3, pre-dose, Day 3, 24 h and Follow-up (Day 7)]
12-lead ECGs were obtained at each timepoint during the study using an ECG machine that automatically calculated the heart rate and measures RR, PR, QRS, QT, and QTc intervals. Absolute mean values of PR, QRS, QT, and QTcB, QTcF, RR intervals were reported.
Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) [Up to Follow-up (Day 7)]
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Secondary Outcome Measures

Mean Serum Interleukin-6 Levels [6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1]
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of Serum interleukin-6 levels at these specified time oints were reported.
Mean Serum CXCL8 (Interleuin-8) Levels [6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1]
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of Serum CXCL8 (Interleuin-8) levels at these specified time points were reported.
Mean Serum C-Reactive Protein (CRP) Levels [6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1]
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of serum CRP levels at these specified time points were reported.
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I [6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1]
Samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of soluble tumor necrosis factor receptors-I levels at these specified time points were reported.
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels [6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1]
Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of MPO levels at these specified time points were reported.
Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) [For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose)]
Absolute values of the mean AUC 0-24 of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h10minutes [min], 24h45min, 27, 34, 40, 80 h since doing on Day 3).
Mean Average Concentration (Cavg) of SB-681323 [For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10minutes [min], 24h 45min, 27, 34, 40, 80 h since doing on Day 3)]
Absolute values of mean Cavg of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3).
Maximum Observed Concentration (Cmax) of SB-681323 [For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3)]
Absolute values of the Cmax of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

Male or female, 18 - 80 years of age (inclusive) with major trauma admitted to the Intensive Care Unit (ICU).
Injury Severity score (ISS) >16 to <70 (exclusive)
A female subject is eligible to participate if she is of non-child-bearing potential or of:
Child-bearing potential and agrees to use one of the approved contraception methods (oral contraceptive, either combined or progesterone alone, injectable progesterone, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device (IUD) or intrauterine system (IUS) with less than 1% non-effectiveness, documented male partner sterilization, double barrier method, i.e. condom and occlusive cap plus spermicidal agent) for an appropriate period of time (as determined by the product label or investigator, if applicable. Female subjects must agree to use contraception until one week post-last dose, if applicable.
Male subjects must agree to use one of the approved contraception methods (abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject, condom during non-vaginal intercourse with any partner (male or female), condom and occlusive cap plus spermicidal agent during sexual intercourse with a female) if applicable. This criterion must be followed from the time of the first dose of study medication until one week post-last dose, if applicable.
BMI within the range 19.0 - 35.0 kg/m2 inclusive (clinical estimate of height and weight is acceptable).
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 < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
The subject must be randomized into the study within 24-26 hours from the time of trauma.

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

Known positive Hepatitis B surface antigen or Hepatitis C antibody.
Known positive test for HIV antibody.
A known history of substance abuse, alcohol abuse, or regular alcohol consumption within 6 months of the study defined as:
an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
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).
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.
Haemoglobin < 7g/dL.
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.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Diagnosis of ALI at admission.
Head trauma (Abbreviated Injury Score [AIS]>3), liver trauma (AIS>2), or trauma that in the opinion of the Principle Investigator or GSK medical monitor is deemed unsurvivable.
Known history of neuromuscular disease or cord injury at C5 or above.
Elevated ALT or AST > 1.5 ULN.
History of bone marrow or solid organ transplant.
Known history of auto-immune disorder in which immunosuppressive agents, other than prednisone, were required within the last 6 weeks.
Known to be receiving oral or intravenous corticosteroids within 7 days of admission.
Subject with active tuberculosis or being treated for active tuberculosis.
Known history of malignancy within the past 5 years with the exception of successfully treated squamous cell or basal cell cancer of the skin.
Arterial blood pH less than 7.1 or serum HCO3 - <15 before infusion is started.
Persistent cardiovascular instability requiring therapy with more than one vasopressor.
A patient will be excluded if in the judgement of the Principle Investigator or GSK medical monitor their participation could jeopardize the health of the subject or the integrity of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Lexington	Kentucky	United States	40536-0293
2	GSK Investigational Site	Durham	North Carolina	United States	27710
3	GSK Investigational Site	Winston-Salem	North Carolina	United States	27157
4	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
5	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213
6	GSK Investigational Site	Nashville	Tennessee	United States	37232-7110

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00996840

Other Study ID Numbers:

111592

First Posted:

Oct 16, 2009

Last Update Posted:

Oct 18, 2017

Last Verified:

Sep 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by GlaxoSmithKline

dilmapimod

p38

SB-681323

Acute Lung Injury (ALI)

Acute Respiratory Distress Syndrome (ARDS)

Additional relevant MeSH terms:

Respiratory Distress Syndrome

Acute Lung Injury

Lung Injury

Wounds and Injuries

Study Results

Participant Flow

Recruitment Details	This study was conducted across 6 centers in the United States, with 5 centers actually enrolling participants. The first participant was enrolled on 16-October-2009 and the last participant completed the study on 09-February-2013.
Pre-assignment Detail	Seventy seven participants were randomized in the study and were included in All subject population.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo intravenous (IV) infusion over 4 hours (h) or 24 h for 3 days	Eligible participants received SB-681323, 3 milligrams (mg), IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Period Title: Overall Study
STARTED	20	9	12	18	18
COMPLETED	19	7	11	17	16
NOT COMPLETED	1	2	1	1	2

Baseline Characteristics

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h	Total
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days	Total of all reporting groups
Overall Participants	20	9	12	18	18	77
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.2 (17.70)	47.4 (19.31)	34.5 (15.61)	44.1 (15.89)	46.1 (21.80)	42.7 (18.24)
Sex: Female, Male (Count of Participants)
Female	3 15%	3 33.3%	1 8.3%	4 22.2%	5 27.8%	16 20.8%
Male	17 85%	6 66.7%	11 91.7%	14 77.8%	13 72.2%	61 79.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 5.6%	0 0%	1 1.3%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	8 40%	0 0%	3 25%	3 16.7%	4 22.2%	18 23.4%
White	11 55%	9 100%	8 66.7%	12 66.7%	13 72.2%	53 68.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5%	0 0%	1 8.3%	2 11.1%	1 5.6%	5 6.5%

Outcome Measures

1. Primary Outcome

Title	Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count
Description	Mean hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, white blood cell count were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject Population comprised of as all participant who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Basophils: Day 2, pre-dose	0.0305 (0.04196)	0.0163 (0.01188)	0.0208 (0.02843)	0.0153 (0.01125)	0.0258 (0.02134)
Basophils: Day 3, pre-dose	0.0291 (0.03036)	0.0129 (0.00756)	0.0209 (0.02737)	0.0176 (0.01562)	0.0279 (0.03191)
Basophils: Day 3, 24 h	0.0239 (0.02062)	0.0294 (0.02809)	0.0300 (0.02374)	0.0284 (0.02762)	0.0315 (0.04240)
Basophils: Follow up (Day 7)	0.0389 (0.03660)	0.0314 (0.02340)	0.0300 (0.02625)	0.0345 (0.03965)	0.0240 (0.02501)
Eosinophils: Day 2, pre-dose	0.0968 (0.18817)	0.0676 (0.07149)	0.0633 (0.07451)	0.0331 (0.04319)	0.0724 (0.07411)
Eosinophils: Day 3, pre-dose	0.1588 (0.18027)	0.0894 (0.06882)	0.0964 (0.10112)	0.0746 (0.06376)	0.0664 (0.04955)
Eosinophils: Day 3, 24 h	0.2544 (0.18852)	0.1538 (0.07558)	0.1400 (0.14365)	0.1345 (0.12560)	0.1142 (0.07005)
Eosinophils: Follow up (Day 7)	0.3713 (0.29748)	0.2866 (0.25120)	0.1900 (0.16445)	0.2390 (0.08483)	0.1998 (0.14855)
Lymphocytes: Day 2, pre-dose	1.2943 (0.68932)	0.9725 (0.43980)	1.0575 (0.49116)	1.3276 (0.57791)	1.5365 (0.83119)
Lymphocytes: Day 3, pre-dose	1.2594 (0.59834)	1.0103 (0.39949)	1.0582 (0.42171)	1.1462 (0.52784)	1.1593 (0.55383)
Lymphocytes: Day 3, 24 h	1.1146 (0.44206)	1.0406 (0.36407)	1.0067 (0.60161)	1.1936 (0.50190)	1.4288 (0.62231)
Lymphocytes: Follow up (Day 7)	1.4967 (0.53371)	1.0611 (0.31455)	1.0370 (0.50228)	1.3915 (0.72178)	1.2835 (0.41700)
Monocytes: Day 2, pre-dose	0.8503 (0.36457)	0.6670 (0.16724)	0.7900 (0.20432)	0.9588 (0.53966)	0.7246 (0.24992)
Monocytes: Day 3, pre-dose	0.7726 (0.35421)	0.6564 (0.20882)	0.5936 (0.24072)	0.8479 (0.54882)	0.6957 (0.22589)
Monocytes: Day 3, 24 h	0.8554 (0.32384)	0.6238 (0.16501)	0.7308 (0.23372)	0.8852 (0.33731)	0.6712 (0.29185)
Monocytes: Follow up (Day 7)	1.1119 (0.50819)	0.9531 (0.45374)	0.9030 (0.45314)	1.1811 (0.42979)	0.7591 (0.23030)
Total Neutrophils: Day 2, pre-dose	9.1607 (2.78517)	7.0729 (2.28843)	9.0225 (3.17595)	9.4199 (2.80762)	8.2319 (2.78227)
Total Neutrophils: Day 3, pre-dose	8.3494 (2.81972)	6.8724 (2.39872)	8.6555 (4.16819)	8.3912 (3.64530)	8.1779 (2.36852)
Total Neutrophils: Day 3, 24 h	8.0317 (2.21593)	5.4550 (2.01330)	7.7675 (2.93749)	8.4700 (3.48850)	6.9604 (3.51501)
Total Neutrophils: Follow up (Day 7)	9.7596 (3.53180)	7.8463 (3.49800)	9.4750 (3.26687)	9.7576 (4.00884)	8.4943 (4.71139)
Platelet count: Day 2, pre-dose	139.5 (46.84)	109.6 (36.21)	152.0 (60.65)	145.2 (52.96)	149.5 (45.73)
Platelet count: Day 3, pre-dose	143.1 (54.62)	124.5 (39.16)	152.4 (66.02)	144.6 (44.73)	144.1 (39.33)
Platelet count: Day 3, 24 h	172.0 (58.25)	138.9 (28.15)	177.3 (68.96)	183.1 (53.62)	176.1 (44.35)
Platelet count: Follow up (Day 7)	310.1 (87.28)	262.4 (76.44)	253.6 (84.79)	284.0 (84.37)	300.6 (105.65)
White blood cell count: Day 2, pre-dose	11.17 (3.394)	8.80 (2.480)	10.95 (3.028)	11.67 (3.377)	10.88 (3.068)
White blood cell count: Day 3, pre-dose	10.43 (3.482)	8.55 (2.206)	10.38 (4.105)	10.47 (4.112)	10.36 (2.370)
White blood cell count: Day 3, 24 h	10.26 (2.544)	7.26 (1.859)	9.68 (2.954)	10.72 (3.694)	9.78 (3.316)
White blood cell count: Follow up (Day 7)	12.84 (3.894)	10.73 (3.973)	11.34 (3.312)	13.60 (5.614)	11.18 (5.237)

2. Primary Outcome

Title	Mean Hematology Parameters- Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
Description	Mean hematology parameters including hemoglobin, MCHC were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Hemoglobin : Day 2, pre-dose	100.8 (17.05)	97.0 (16.27)	97.8 (22.04)	88.4 (12.46)	97.2 (20.40)
Hemoglobin : Day 3, pre-dose	90.6 (15.27)	96.0 (17.48)	93.7 (19.40)	82.9 (9.29)	95.2 (20.85)
Hemoglobin : Day 3, 24 h	91.9 (12.94)	96.5 (16.50)	93.0 (15.36)	84.7 (9.73)	95.1 (19.37)
Hemoglobin: follow up (Day 7)	94.1 (14.97)	103.5 (16.42)	99.6 (15.49)	88.8 (8.93)	99.2 (16.36)
MCHC :Day 2, pre-dose	341.2 (10.96)	343.8 (4.17)	339.3 (6.96)	339.1 (9.43)	343.6 (10.63)
MCHC : Day 3, pre-dose	337.4 (9.30)	343.1 (8.15)	338.7 (7.64)	339.1 (7.43)	341.2 (8.73)
MCHC : Day 3, 24 h	338.2 (9.33)	342.9 (6.90)	338.1 (9.34)	336.4 (10.03)	342.8 (9.60)
MCHC : Follow up (Day 7)	333.4 (12.09)	339.5 (10.74)	337.8 (9.72)	331.1 (11.89)	342.5 (9.28)

3. Primary Outcome

Title	Mean Hematology Parameters- Mean Corpuscle Hemoglobin
Description	Hematology parameter mean corpuscle hemoglobin was reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Mean Corpuscle Hemoglobin: Day 2, pre-dose	30.46 (1.340)	30.74 (1.241)	30.11 (1.262)	30.18 (1.997)	31.10 (1.160)
Mean Corpuscle Hemoglobin: Day 3, pre-dose	30.21 (1.319)	30.78 (1.290)	30.22 (1.135)	30.19 (1.771)	30.77 (1.332)
Mean Corpuscle Hemoglobin: Day 3, 24 h	30.25 (1.359)	30.80 (1.153)	30.33 (1.378)	30.06 (1.808)	30.92 (1.274)
Mean Corpuscle Hemoglobin:Follow up (Day 7)	30.02 (1.141)	30.64 (1.308)	30.13 (1.234)	29.82 (1.768)	31.08 (1.415)

4. Primary Outcome

Title	Hematology Parameters-Mean Corpuscle Volume
Description	Absolute values of mean corpuscle volume were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Mean Corpuscle Volume:Day 2, pre-dose	89.30 (4.024)	89.59 (3.379)	88.33 (3.367)	89.15 (4.828)	90.63 (2.809)
Mean Corpuscle Volume: Day 3, pre-dose	89.85 (3.833)	89.70 (2.804)	89.00 (3.742)	89.18 (4.375)	90.48 (3.075)
Mean Corpuscle Volume: Day 3, 24 h	89.41 (3.920)	89.96 (2.295)	89.50 (3.920)	89.45 (4.285)	90.08 (2.510)
Mean Corpuscle Volume: Follow up (Day 7)	90.12 (3.430)	89.86 (2.738)	89.67 (3.869)	90.43 (4.079)	90.75 (3.115)

5. Primary Outcome

Title	Mean Hematology Parameters-reticulocytes, Red Blood Cell Count
Description	Absolute values of reticulocytes and red blood cell count were reported. If sample for hematology test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Reticulocytes : Day 2, pre-dose	0.0488 (0.01974)	0.0411 (0.01902)	0.0406 (0.00863)	0.0398 (0.01218)	0.0513 (0.02192)
Reticulocytes : Day 3, pre-dose	0.0554 (0.01871)	0.0448 (0.01903)	0.0464 (0.01284)	0.0474 (0.01382)	0.0576 (0.02543)
Reticulocytes : Day 3, 24 h	0.0662 (0.02171)	0.0592 (0.02654)	0.0538 (0.01876)	0.0581 (0.01748)	0.0699 (0.02818)
Reticulocytes : Follow up (Day 7)	0.0934 (0.04509)	0.0979 (0.04134)	0.0829 (0.05170)	0.0897 (0.03964)	0.1213 (0.06734)
Red Blood Cell count : Day 2, pre-dose	3.320 (0.6164)	3.151 (0.4434)	3.253 (0.6883)	2.943 (0.4695)	3.121 (0.6197)
Red Blood Cell count : Day 3, pre-dose	3.007 (0.5787)	3.110 (0.5001)	3.103 (0.6117)	2.758 (0.3615)	3.083 (0.6114)
Red Blood Cell count : Day 3, 24 h	3.054 (0.5220)	3.128 (0.4706)	3.071 (0.5146)	2.822 (0.3372)	3.062 (0.5799)
Red Blood Cell count : Follow up (Day 7)	3.144 (0.5268)	3.379 (0.4695)	3.313 (0.5365)	2.983 (0.3445)	3.183 (0.4403)

6. Primary Outcome

Title	Mean Clinical Chemistry Parameters- Albumin and Total Protein
Description	Absolute values of albumin and total protein were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Albumin : Day 2, pre-dose	25.2 (4.27)	25.1 (5.72)	23.7 (3.69)	26.2 (3.45)	24.7 (5.33)
Albumin : Day 3, pre-dose	22.8 (4.29)	25.6 (4.96)	22.6 (5.45)	23.1 (3.51)	25.1 (6.06)
Albumin : Day 3, 24 h	22.4 (3.99)	24.1 (4.56)	22.7 (4.85)	22.6 (3.90)	24.3 (6.69)
Albumin : Follow up (Day 7)	22.4 (6.34)	25.5 (4.87)	21.6 (4.74)	22.0 (3.86)	26.8 (5.03)
Total Protein : Day 2, pre-dose	49.4 (7.39)	47.1 (9.44)	46.8 (7.64)	48.9 (5.76)	51.1 (9.21)
Total Protein : Day 3, pre-dose	47.8 (8.01)	50.0 (7.02)	46.3 (9.24)	47.1 (3.82)	52.7 (11.24)
Total Protein : Day 3, 24 h	51.4 (7.09)	49.6 (3.82)	49.2 (7.78)	49.0 (5.00)	53.2 (10.99)
Total Protein : Follow up (Day 7)	55.8 (9.54)	55.6 (4.27)	50.3 (8.66)	52.3 (7.41)	58.5 (8.55)

7. Primary Outcome

Title	Mean Clinical Chemistry Parameters-alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
Description	Absolute values of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and gamma glutamyl transferase were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Alkaline phosphatase : Day 2, pre-dose	52.0 (19.99)	53.8 (12.53)	43.5 (8.19)	49.4 (21.15)	52.2 (17.98)
Alkaline phosphatase : Day 3, pre-dose	52.6 (20.35)	73.1 (45.57)	48.6 (11.07)	50.8 (26.85)	55.6 (18.92)
Alkaline phosphatase : Day 3, 24 h	66.6 (37.08)	76.0 (44.67)	53.5 (13.19)	60.6 (34.38)	59.5 (25.61)
Alkaline phosphatase : Follow up (Day 7)	89.3 (57.58)	118.1 (58.77)	69.8 (39.40)	94.5 (59.93)	90.0 (60.86)
Alanine Amino Transferase : Day 2, pre-dose	51.1 (26.48)	37.8 (26.63)	60.5 (37.89)	45.4 (22.67)	53.8 (49.17)
Alanine Amino Transferase : Day 3, pre-dose	43.1 (18.64)	43.4 (48.84)	50.8 (26.93)	37.5 (15.91)	41.4 (32.89)
Alanine Amino Transferase : Day 3, 24 h	44.7 (21.93)	53.3 (62.19)	49.1 (21.82)	34.3 (15.14)	42.3 (29.56)
Alanine Amino Transferase : Follow up (Day 7)	52.5 (50.95)	77.4 (58.39)	117.8 (158.33)	42.2 (21.73)	59.1 (52.41)
Aspartate Amino Transferase : Day 2, pre-dose	74.6 (42.35)	57.1 (28.41)	125.2 (65.22)	83.2 (40.61)	81.4 (53.72)
Aspartate Amino Transferase : Day 3, pre-dose	73.3 (62.80)	64.9 (58.77)	90.5 (44.66)	65.8 (31.23)	62.3 (29.70)
Aspartate Amino Transferase : Day 3, 24 h	77.5 (93.43)	81.3 (79.91)	84.9 (37.84)	53.1 (29.14)	71.9 (66.70)
Aspartate Amino Transferase : Follow up (Day 7)	57.9 (46.83)	64.9 (31.73)	137.1 (192.21)	48.3 (21.76)	65.6 (59.80)
Creatine Kinase : Day 2, pre-dose	3287.8 (3333.83)	1174.0 (996.71)	4663.1 (4797.79)	2797.2 (2022.44)	2527.8 (2507.94)
Creatine Kinase : Day 3, pre-dose	2668.0 (4149.97)	1183.8 (944.80)	4418.9 (5201.64)	2307.0 (1670.81)	2418.9 (3267.70)
Creatine Kinase : Day 3, 24 h	2527.4 (5594.82)	1638.3 (2178.26)	3342.3 (2222.65)	1410.2 (1417.50)	1227.8 (1038.81)
Creatine Kinase : Follow up (Day 7)	954.3 (2023.51)	503.8 (725.49)	1349.9 (1296.97)	602.1 (476.66)	366.4 (329.52)
Gamma Glutamyl Transferase : Day 2, pre-dose	25.2 (20.05)	20.8 (8.80)	34.0 (46.54)	26.3 (23.01)	17.3 (11.67)
Gamma Glutamyl Transferase : Day 3, pre-dose	27.3 (23.02)	23.0 (9.81)	25.4 (15.36)	23.7 (18.42)	26.9 (31.60)
Gamma Glutamyl Transferase : Day 3, 24 h	39.4 (47.61)	31.3 (22.68)	38.4 (33.91)	43.4 (46.70)	39.3 (54.64)
Gamma Glutamyl Transferase : Follow up (Day 7)	75.9 (61.62)	70.6 (49.58)	48.3 (41.93)	86.7 (90.58)	45.6 (46.01)

8. Primary Outcome

Title	Mean Clinical Chemistry Parameters- Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid
Description	Absolute values of direct bilirubin, total bilirubin, creatinine and uric acid were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Direct Bilirubin : Day 2, pre-dose	4.500 (1.6333)	4.275 (2.0438)	8.705 (11.6846)	5.985 (6.9250)	3.306 (1.6436)
Direct Bilirubin : Day 3, pre-dose	4.590 (1.9789)	4.275 (1.5832)	6.995 (7.2329)	6.840 (9.5974)	3.420 (2.2076)
Direct Bilirubin : Day 3, 24 h	5.890 (4.0305)	4.703 (2.5446)	7.773 (10.6340)	6.639 (9.7463)	4.998 (4.1572)
Direct Bilirubin : Follow up (Day 7)	7.110 (5.7923)	7.695 (8.7671)	26.030 (58.4146)	10.964 (22.2140)	9.120 (16.4864)
Total Bilirubin : Day 2, pre-dose	19.238 (9.9071)	17.314 (8.7403)	24.717 (16.4971)	15.675 (8.8223)	18.145 (14.8048)
Total Bilirubin : Day 3, pre-dose	18.126 (6.1128)	16.245 (5.9937)	20.520 (14.7497)	18.408 (11.8245)	15.604 (6.7214)
Total Bilirubin : Day 3, 24 h	20.430 (7.6574)	19.238 (8.1112)	21.608 (15.0494)	19.615 (12.2882)	18.596 (9.6505)
Total Bilirubin : Follow up (Day 7)	20.880 (8.4271)	24.581 (15.2383)	53.390 (98.8728)	26.656 (30.4820)	22.978 (22.7112)
Creatinine : Day 2, pre-dose	76.6428 (23.25282)	83.4275 (49.48807)	87.9982 (34.95181)	90.9538 (66.75768)	80.1984 (32.87944)
Creatinine : Day 3, pre-dose	71.1620 (22.69678)	80.2230 (51.77845)	87.9178 (53.40174)	87.4640 (65.10727)	72.9560 (31.73042)
Creatinine : Day 3, 24 h	69.9756 (22.20243)	73.0405 (45.07022)	89.7260 (84.44314)	90.8960 (91.11701)	78.1788 (28.17353)
Creatinine : Follow up (Day 7)	70.7200 (25.41831)	71.8250 (31.43842)	85.9690 (61.38913)	98.7480 (110.4008)	76.9080 (35.07431)
Uric acid : Day 2, pre-dose	200.7450 (79.77454)	207.4365 (76.26689)	194.1211 (99.68084)	246.5116 (96.00019)	231.9720 (76.04761)
Uric acid : Day 3, pre-dose	185.2802 (76.68988)	202.9755 (83.29855)	202.7727 (83.20631)	233.3715 (101.8900)	226.4205 (79.05205)
Uric acid : Day 3, 24 h	190.6491 (75.69201)	194.0535 (90.48210)	192.4989 (95.58615)	222.8751 (115.7210)	247.0403 (87.73096)
Uric acid : Follow up (Day 7)	174.4747 (74.95979)	171.0050 (62.36289)	188.8490 (106.1990)	221.4755 (129.6427)	253.7813 (118.3352)

9. Primary Outcome

Title	Mean Clinical Chemistry Parameters- Calcium, Chloride, Glucose, Bicarbonate, Potassium, Sodium and Ratio of Urea to Blood Urea Nitrogen (Urea/BUN)
Description	Absolute values of calcium, chloride, glucose, bicarbonate, potassium, sodium and Urea/BUN were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Calcium : Day 2, pre-dose	1.9523 (0.11501)	1.9274 (0.12913)	1.9098 (0.11828)	1.9489 (0.08889)	1.9655 (0.13867)
Calcium : Day 3, pre-dose	1.9523 (0.10857)	1.9835 (0.11158)	1.9007 (0.08411)	1.9314 (0.12383)	1.9887 (0.15273)
Calcium : Day 3, 24 h	1.9881 (0.09701)	2.0272 (0.09312)	1.9565 (0.15138)	1.9432 (0.09120)	2.0116 (0.15132)
Calcium : Follow up (Day 7)	2.0617 (0.14021)	2.0989 (0.12612)	2.0005 (0.15773)	2.0386 (0.11794)	2.0958 (0.14441)
Chloride : Day 2, pre-dose	106.5 (5.04)	105.5 (4.69)	107.5 (3.62)	106.3 (4.17)	105.3 (4.75)
Chloride : Day 3, pre-dose	106.3 (5.66)	105.5 (4.93)	107.7 (4.67)	105.9 (5.89)	105.7 (4.25)
Chloride : Day 3, 24 h	104.6 (5.12)	104.4 (4.98)	106.0 (5.54)	106.4 (5.84)	105.3 (4.41)
Chloride : Follow up (Day 7)	105.2 (7.84)	101.8 (4.59)	106.2 (5.13)	104.5 (6.07)	102.2 (3.15)
Glucose : Day 2, pre-dose	6.8028 (2.22918)	8.0628 (1.92721)	6.9690 (1.03682)	7.8763 (2.30585)	7.3797 (4.08342)
Glucose : Day 3, pre-dose	6.7889 (1.93504)	7.2094 (1.67306)	6.2878 (1.22124)	7.8530 (2.96473)	6.2530 (0.98343)
Glucose : Day 3, 24 h	7.6575 (4.44567)	6.2865 (1.01307)	6.1662 (0.84863)	7.7192 (3.27506)	6.0321 (1.32273)
Glucose : Follow up (Day 7)	6.6115 (1.95391)	6.3698 (0.55172)	6.4139 (1.50295)	6.9110 (2.14454)	6.2563 (1.41547)
Bicarbonate : Day 2, pre-dose	26.0 (2.73)	25.9 (2.36)	25.6 (2.11)	25.9 (2.55)	25.6 (2.20)
Bicarbonate : Day 3, pre-dose	27.2 (1.96)	27.8 (2.92)	26.5 (2.91)	26.5 (3.47)	25.7 (2.69)
Bicarbonate : Day 3, 24 h	27.7 (2.70)	28.5 (2.62)	27.3 (3.86)	26.6 (2.18)	25.3 (2.59)
Bicarbonate : Follow up (Day 7)	27.3 (2.75)	27.3 (2.49)	28.3 (1.91)	27.1 (2.67)	26.7 (3.14)
Potassium : Day 2, pre-dose	4.22 (0.558)	3.89 (0.348)	4.17 (0.374)	4.10 (0.468)	4.12 (0.342)
Potassium : Day 3, pre-dose	3.88 (0.318)	3.96 (0.267)	4.15 (0.491)	4.00 (0.550)	3.99 (0.376)
Potassium : Day 3, 24 h	3.85 (0.347)	3.91 (0.280)	3.93 (0.442)	3.91 (0.496)	3.95 (0.449)
Potassium : Follow up (Day 7)	4.01 (0.435)	4.01 (0.473)	3.70 (0.357)	3.99 (0.405)	3.98 (0.256)
Sodium : Day 2, pre-dose	137.1 (3.61)	136.3 (3.45)	136.7 (3.44)	136.7 (2.97)	137.2 (4.02)
Sodium : Day 3, pre-dose	138.0 (3.91)	138.4 (3.29)	138.5 (3.80)	137.6 (3.69)	138.1 (3.66)
Sodium : Day 3, 24 h	138.2 (4.15)	137.9 (3.48)	138.5 (3.09)	138.4 (3.86)	137.9 (3.24)
Sodium : Follow up (Day 7)	139.6 (5.96)	137.1 (4.97)	140.2 (5.22)	139.0 (5.05)	136.6 (3.06)
Urea/BUN : Day 2, pre-dose	3.7664 (2.13093)	3.4361 (3.16986)	4.3392 (3.00056)	4.9385 (3.44877)	4.6013 (2.85045)
Urea/BUN : Day 3, pre-dose	3.4808 (1.57061)	3.7485 (3.85447)	4.9655 (4.52265)	4.8510 (3.92306)	4.6200 (2.93162)
Urea/BUN : Day 3, 24 h	4.1525 (2.34164)	4.3286 (4.26883)	4.9683 (6.06128)	5.4390 (5.13095)	4.8418 (2.59399)
Urea/BUN : Follow up (Day 7)	5.9938 (5.08449)	6.0244 (4.20870)	6.2313 (7.18868)	7.1610 (8.27331)	5.3340 (2.80100)

10. Primary Outcome

Title	Mean Clinical Chemistry Parameters-estradiol
Description	Absolute values of Estradiol were reported. If sample for clinical chemistry test had been obtained for standard of care within ± 4 h of the planned assessment then it was not collected at the planned assessment time point.
Time Frame	Day 1 (pre-dose) and Day 3 (24 h)

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed. Data were not collected from participants in Cohort 2-SB-681323, 7.5 mg, 24 h, Cohort 3-SB-681323, 7.5 mg, 4 h, and Cohort 4-SB-681323, 10 mg, 24 h.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	1	4	0	0	0
Mean (Standard Deviation) [Picomole per liter]	165.150 (NA)	210.108 (100.8360)

11. Primary Outcome

Title	Mean Clinical Chemistry Parameters-Blood pH at Screening
Description	Absolute values of Blood pH at screening were reported as clinical chemistry parameter.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	16	6	8	11	9
Mean (Standard Deviation) [pH Units]	7.358 (0.0738)	7.363 (0.0824)	7.358 (0.0354)	7.353 (0.0297)	7.373 (0.0527)

12. Primary Outcome

Title	Vital Parameter- Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description	Absolute values of SBP and DBP were reported.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
SBP : Day 1, 4 h	127.9 (20.93)	116.6 (17.33)	130.4 (16.25)
SBP : Day 2, Pre-dose	126.4 (19.91)	114.8 (13.72)	130.3 (23.72)	130.9 (24.15)	127.1 (21.47)
SBP : Day 3, Pre-dose	130.5 (22.65)	119.8 (16.65)	140.4 (35.28)	127.9 (21.43)	136.0 (23.57)
SBP : Day 3, Pre-dose 24 H	138.7 (22.18)	136.0 (23.66)	130.3 (22.80)	129.5 (20.23)	128.6 (15.29)
SBP : Follow up (Day 7)	132.4 (19.50)	125.5 (14.06)	134.3 (14.10)	132.6 (27.34)	137.9 (18.57)
DBP : Day 1, 4 h	64.6 (11.57)	61.8 (19.44)	67.6 (11.01)
DBP : Day 2, Pre-dose	63.9 (10.38)	63.8 (11.57)	58.9 (8.68)	65.0 (12.28)	61.7 (14.59)
DBP : Day 3, Pre-dose	65.4 (12.04)	63.4 (11.26)	65.3 (13.45)	64.6 (13.70)	71.2 (15.42)
DBP : Day 3, Pre-dose 24 H	69.2 (11.10)	68.9 (10.99)	68.9 (12.48)	66.2 (11.09)	74.5 (10.92)
DBP : Follow up (Day 7)	66.0 (12.42)	67.9 (12.23)	71.0 (9.82)	69.3 (13.31)	74.0 (12.69)

13. Primary Outcome

Title	Vital Parameter: Mean Heart Rate
Description	Absolute values of mean heart rate were reported.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Heart rate: Day 1, 4 h	92.7 (12.18)	89.7 (17.63)	97.8 (15.37)
Heart rate: Day 2, pre-dose	99.8 (16.92)	93.8 (13.35)	98.1 (27.01)	97.1 (19.36)	82.7 (13.52)
Heart rate: Day 3, pre-dose	97.0 (15.13)	99.3 (19.90)	88.7 (24.73)	93.8 (12.20)	88.3 (17.83)
Heart rate: Day 3, 24 h	100.4 (15.20)	99.3 (12.69)	93.7 (16.37)	96.4 (15.74)	90.5 (18.49)
Heart rate: Follow up (Day 7)	97.6 (13.42)	93.3 (19.91)	100.3 (18.79)	96.8 (16.40)	87.7 (14.09)

14. Primary Outcome

Title	Vital Sign: Mean Percent Oxygen (O2) in Blood
Description	Absolute values of mean percent O2 in blood were reported.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h" and "Follow up (Day 7)"; for Cohort 2 and 4: "Day 2, pre-dose", "Day 3, pre-dose and 24 h", and "Follow up (Day 7)"

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Percent O2 in blood: Day 1, 4 h	98.6 (2.30)	97.1 (2.98)	97.6 (1.65)
Percent O2 in blood: Day 2, pre-dose	97.5 (2.44)	97.3 (2.05)	97.3 (2.87)	96.8 (3.32)	97.1 (3.08)
Percent O2 in blood: Day 3, pre-dose	97.1 (2.40)	96.0 (4.00)	96.9 (2.88)	97.7 (2.49)	96.5 (2.90)
Percent O2 in blood: Day 3, 24 h	97.3 (2.27)	97.9 (2.03)	96.7 (2.41)	97.5 (2.60)	97.3 (2.47)
Percent O2 in blood: Follow up (Day 7)	96.5 (2.06)	97.3 (2.12)	96.3 (3.11)	97.2 (1.99)	97.1 (1.81)

15. Primary Outcome

Title	Vital Signs: Mean Oxygen Saturation (SaO2) Via Pulse Oximetry
Description	Assessment of SaO2 via pulse oximetry was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Outcome Measure Data

Analysis Population Description
All subject population. Data was not collected for this parameter.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	0	0	0	0	0

16. Primary Outcome

Title	Vital Signs: Mean Level of Positive End Expiratory Pressure
Description	Assessment of level of positive end expiratory pressure was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Outcome Measure Data

Analysis Population Description
All subject population. Data was not collected for this parameter.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	0	0	0	0	0

17. Primary Outcome

Title	Vital Signs: Mean Level of Peak and Plateau Ventilator Pressures
Description	Assessment of mean level of peak and plateau ventilator pressures was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Outcome Measure Data

Analysis Population Description
All subject population. Data was not collected for this parameter.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	0	0	0	0	0

18. Primary Outcome

Title	Vital Signs: Mean Oxygen Requirement (FiO2) Via Pulse Oximetry
Description	Assessment of mean FiO2 via pulse oximetry was planned for cohort 1 and 3 at Day 1 (4 h), Day 2 (pre-dose) and Day 3 (pre-dose and 24 h) and for cohort 2 and 4: Day 2 (pre-dose) and Day 3 (pre-dose and 24 h). However, the analyzable data was not collected for this parameter.
Time Frame	For Cohort 1 and 3: "Day 1, 4 h", "Day 2, pre-dose", "Day 3, pre-dose and 24 h"; for Cohort 2 and 4: "Day 2, pre-dose", and "Day 3, pre-dose and 24 h"

Outcome Measure Data

Analysis Population Description
All subject population. Data was not collected for this parameter.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	0	0	0	0	0

19. Primary Outcome

Title	Mean Electrocardiogram (ECG) Parameters Including PR, QRS, QT, and QTcB, QTcF, RR Intervals
Description	12-lead ECGs were obtained at each timepoint during the study using an ECG machine that automatically calculated the heart rate and measures RR, PR, QRS, QT, and QTc intervals. Absolute mean values of PR, QRS, QT, and QTcB, QTcF, RR intervals were reported.
Time Frame	Day 2, pre-dose, Day 3, pre-dose, Day 3, 24 h and Follow-up (Day 7)

Outcome Measure Data

Analysis Population Description
All subject population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
PR Interval: Day 2, pre-dose	141.4 (14.35)	145.5 (21.21)	141.5 (17.80)	143.9 (30.54)	152.9 (20.98)
PR Interval: Day 3, pre-dose	145.7 (20.73)	142.0 (22.33)	141.6 (27.43)	148.6 (23.00)	152.0 (25.88)
PR Interval: Day 3, 24 h	137.0 (18.90)	146.9 (34.15)	142.2 (24.93)	145.9 (21.21)	160.7 (23.58)
PR Interval: Follow up (Day 7)	133.9 (13.85)	142.8 (24.33)	142.0 (16.54)	138.1 (26.91)	155.1 (22.63)
QRS Duration: Day 2, pre-dose	89.8 (9.26)	86.5 (10.78)	86.8 (12.49)	87.2 (13.34)	88.0 (12.63)
QRS Duration: Day 3, pre-dose	90.5 (9.62)	87.1 (8.86)	89.5 (10.66)	87.6 (14.56)	86.5 (12.11)
QRS Duration: Day 3, 24 h	91.6 (10.48)	85.7 (7.70)	90.6 (8.85)	88.3 (14.36)	88.4 (12.29)
QRS Duration: Follow up (Day 7)	90.8 (9.39)	86.0 (8.42)	88.5 (11.35)	85.4 (14.01)	85.9 (10.16)
QT Interval: Day 2, pre-dose	338.7 (30.74)	349.5 (29.89)	342.0 (61.77)	332.1 (34.00)	365.1 (39.95)
QT Interval: Day 3, pre-dose	338.6 (34.99)	352.9 (36.20)	351.3 (56.64)	342.5 (24.15)	351.4 (48.51)
QT Interval: Day 3, 24 h	328.8 (35.13)	347.4 (28.93)	340.2 (31.64)	336.5 (31.22)	358.0 (47.32)
QT Interval: Follow up (Day 7)	346.7 (33.16)	352.5 (16.89)	335.0 (47.41)	342.1 (37.14)	369.1 (45.58)
QTcB Interval: Day 2, pre-dose	432.5 (28.82)	427.5 (27.91)	422.0 (28.72)	418.6 (21.72)	416.2 (24.28)
QTcB Interval: Day 3, pre-dose	424.4 (27.55)	443.4 (28.77)	414.4 (22.33)	420.9 (26.99)	427.4 (31.17)
QTcB Interval: Day 3, 24 h	425.8 (21.83)	425.6 (18.45)	418.5 (22.60)	422.5 (22.33)	429.6 (22.05)
QTcB Interval: Follow up (Day 7)	435.5 (32.08)	439.4 (15.30)	430.1 (43.76)	434.7 (19.27)	440.3 (48.93)
QTcF Interval: Day 2, pre-dose	398.3 (24.07)	399.4 (22.88)	392.6 (36.62)	387.1 (22.19)	397.9 (24.09)
QTcF Interval: Day 3, pre-dose	393.3 (27.85)	410.5 (26.01)	391.5 (30.90)	392.7 (21.41)	400.0 (35.34)
QTcF Interval: Day 3, 24 h	390.4 (24.77)	397.4 (14.85)	390.3 (22.25)	391.4 (22.27)	403.7 (26.80)
QTcF Interval: Follow up (Day 7)	403.4 (29.35)	408.1 (11.78)	395.5 (43.63)	401.0 (23.91)	414.9 (45.44)
RR Interval: Day 2, pre-dose	622.0 (117.16)	677.5 (133.48)	667.7 (219.26)	635.5 (119.09)	780.8 (178.59)
RR Interval: Day 3, pre-dose	640.1 (103.46)	641.4 (137.62)	727.9 (210.54)	670.2 (115.37)	679.5 (140.86)
RR Interval: Day 3, 24 h	598.7 (99.54)	675.1 (137.03)	665.8 (114.27)	639.0 (106.37)	703.1 (171.59)
RR Interval: Follow up (Day 7)	639.0 (103.45)	646.8 (74.52)	608.3 (98.05)	622.3 (105.38)	709.0 (112.18)

20. Primary Outcome

Title	Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
Description	AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time Frame	Up to Follow-up (Day 7)

Outcome Measure Data

Analysis Population Description
All subject population.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	9	12	18	18
Any AEs	18 90%	7 77.8%	10 83.3%	16 88.9%	14 77.8%
Any SAEs	1 5%	1 11.1%	1 8.3%	4 22.2%	0 0%

21. Secondary Outcome

Title	Mean Serum Interleukin-6 Levels
Description	Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of Serum interleukin-6 levels at these specified time oints were reported.
Time Frame	6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacodynamic (PD) Population was defined as patients in the 'All Subjects' population for whom a pharmacodynamic sample was obtained and analysed (Flow Cytometry data were excluded from the definition of pharmacodynamic sample). Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	8	10	16	18
Time Since 1st Dose, 6 h	509.44	286.17	391.09	309.57	395.09
Time Since 1st Dose, 12 h	516.49	315.89	362.03	348.23	310.98
Time Since 1st Dose, 18 h	476.94	247.22	275.7	292.24	238.7
Time Since 1st Dose, 24 h	556.06	231.1	228.1	310.47	162.82
Time Since 1st Dose, 48 h	324.35	167.69	290.59	235.13	119.98
Time Since 1st Dose, 72 h	250.21	165.46	184.93	182.54	106.32
Time Since 1st Dose, 96 h	183.79	166.87	286.79	210.87	106.32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.562
	Confidence Interval	(2-Sided) 95% 0.357 to 0.885
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.228
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.612
	Confidence Interval	(2-Sided) 95% 0.349 to 1.072
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.281
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.518
	Confidence Interval	(2-Sided) 95% 0.274 to 0.981
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.319
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.416
	Confidence Interval	(2-Sided) 95% 0.217 to 0.796
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.326
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.517
	Confidence Interval	(2-Sided) 95% 0.262 to 1.021
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.340
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.661
	Confidence Interval	(2-Sided) 95% 0.291 to 1.503
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.410
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.908
	Confidence Interval	(2-Sided) 95% 0.366 to 2.254
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.454
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.768
	Confidence Interval	(2-Sided) 95% 0.520 to 1.134
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.195
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.701
	Confidence Interval	(2-Sided) 95% 0.427 to 1.150
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.248
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.578
	Confidence Interval	(2-Sided) 95% 0.329 to 1.015
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.282
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.410
	Confidence Interval	(2-Sided) 95% 0.231 to 0.728
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.287
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.896
	Confidence Interval	(2-Sided) 95% 0.484 to 1.657
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.308
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.739
	Confidence Interval	(2-Sided) 95% 0.350 to 1.563
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.374
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.560
	Confidence Interval	(2-Sided) 95% 0.659 to 3.697
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.431
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.608
	Confidence Interval	(2-Sided) 95% 0.433 to 0.853
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.170
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.674
	Confidence Interval	(2-Sided) 95% 0.437 to 1.039
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.217
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.613
	Confidence Interval	(2-Sided) 95% 0.374 to 1.004
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.247
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.558
	Confidence Interval	(2-Sided) 95% 0.338 to 0.921
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.251
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.725
	Confidence Interval	(2-Sided) 95% 0.427 to 1.230
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.264
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.730
	Confidence Interval	(2-Sided) 95% 0.384 to 1.386
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.321
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.147
	Confidence Interval	(2-Sided) 95% 0.559 to 2.353
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.359
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.776
	Confidence Interval	(2-Sided) 95% 0.556 to 1.082
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.167
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.602
	Confidence Interval	(2-Sided) 95% 0.394 to 0.919
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.212
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.623
	Confidence Interval	(2-Sided) 95% 0.386 to 1.007
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.240
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.429
	Confidence Interval	(2-Sided) 95% 0.263 to 0.700
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.245
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.502
	Confidence Interval	(2-Sided) 95% 0.299 to 0.842
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.259
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.479
	Confidence Interval	(2-Sided) 95% 0.255 to 0.903
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.317
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.579
	Confidence Interval	(2-Sided) 95% 0.281 to 1.192
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.361
	Estimation Comments

22. Secondary Outcome

Title	Mean Serum CXCL8 (Interleuin-8) Levels
Description	Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of Serum CXCL8 (Interleuin-8) levels at these specified time points were reported.
Time Frame	6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

Outcome Measure Data

Analysis Population Description
PD Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	8	10	16	18
Time Since 1st Dose, 6 h	37.66	18.22	27.34	21.06	21.85
Time Since 1st Dose, 12 h	26.53	18.58	21.00	22.01	17.42
Time Since 1st Dose, 18 h	21.37	14.55	15.49	21.10	15.96
Time Since 1st Dose, 24 h	24.05	16.19	15.75	22.23	15.79
Time Since 1st Dose, 48 h	17.65	16.24	19.62	21.70	13.40
Time Since 1st Dose, 72 h	15.99	15.09	17.19	20.61	15.47
Time Since 1st Dose, 96 h	19.14	17.33	26.32	33.54	14.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.484
	Confidence Interval	(2-Sided) 95% 0.312 to 0.750
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.219
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.700
	Confidence Interval	(2-Sided) 95.000% 0.399 to 1.229
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.282
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.681
	Confidence Interval	(2-Sided) 95.000% 0.370 to 1.254
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.305
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.673
	Confidence Interval	(2-Sided) 95.000% 0.368 to 1.231
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.302
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.920
	Confidence Interval	(2-Sided) 95.000% 0.456 to 1.857
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.351
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.944
	Confidence Interval	(2-Sided) 95.000% 0.445 to 2.002
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.376
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.905
	Confidence Interval	(2-Sided) 95.000% 0.476 to 1.723
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.321
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.726
	Confidence Interval	(2-Sided) 95.000% 0.488 to 1.080
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.199
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.791
	Confidence Interval	(2-Sided) 95.000% 0.476 to 1.317
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.255
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.725
	Confidence Interval	(2-Sided) 95.000% 0.417 to 1.260
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.277
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.655
	Confidence Interval	(2-Sided) 95.000% 0.379 to 1.130
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.273
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.111
	Confidence Interval	(2-Sided) 95.000% 0.583 to 2.120
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.323
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.075
	Confidence Interval	(2-Sided) 95.000% 0.539 to 2.146
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.346
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.375
	Confidence Interval	(2-Sided) 95.000% 0.735 to 2.574
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.313
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.559
	Confidence Interval	(2-Sided) 95.000% 0.400 to 0.783
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.168
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.830
	Confidence Interval	(2-Sided) 95.000% 0.539 to 1.277
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.216
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.987
	Confidence Interval	(2-Sided) 95.00% 0.613 to 1.589
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.238
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.924
	Confidence Interval	(2-Sided) 95.00% 0.582 to 1.467
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.231
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.230
	Confidence Interval	(2-Sided) 95.00% 0.716 to 2.110
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.270
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.289
	Confidence Interval	(2-Sided) 95.00% 0.719 to 2.312
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.292
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.752
	Confidence Interval	(2-Sided) 95.00% 1.053 to 2.916
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.254
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.580
	Confidence Interval	(2-Sided) 95.00% 0.419 to 0.803
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.163
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.657
	Confidence Interval	(2-Sided) 95.00% 0.433 to 0.996
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.209
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.747
	Confidence Interval	(2-Sided) 95.00% 0.477 to 1.171
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.225
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.657
	Confidence Interval	(2-Sided) 95.00% 0.421 to 1.024
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.222
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.759
	Confidence Interval	(2-Sided) 95.00% 0.451 to 1.279
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.261
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.968
	Confidence Interval	(2-Sided) 95.00% 0.550 to 1.701
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.282
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.744
	Confidence Interval	(2-Sided) 95.00% 0.450 to 1.229
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.251
	Estimation Comments

23. Secondary Outcome

Title	Mean Serum C-Reactive Protein (CRP) Levels
Description	Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of serum CRP levels at these specified time points were reported.
Time Frame	6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

Outcome Measure Data

Analysis Population Description
PD Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	8	10	16	18
Time Since 1st Dose, 6 h	123.62	95.60	117.68	117.42	110.88
Time Since 1st Dose, 12 h	138.02	109.74	133.17	136.01	122.42
Time Since 1st Dose, 18 h	144.10	112.06	142.96	153.76	121.97
Time Since 1st Dose, 24 h	153.88	97.42	140.47	141.84	125.02
Time Since 1st Dose, 48 h	159.36	105.45	105.17	138.05	92.50
Time Since 1st Dose, 72 h	179.03	83.21	123.58	116.27	78.55
Time Since 1st Dose, 96 h	171.67	90.20	124.33	123.97	77.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.773
	Confidence Interval	(2-Sided) 95.00% 0.607 to 0.985
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.121
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.795
	Confidence Interval	(2-Sided) 95.00% 0.583 to 1.084
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.155
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.778
	Confidence Interval	(2-Sided) 95.00% 0.533 to 1.135
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.189
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.633
	Confidence Interval	(2-Sided) 95.00% 0.430 to 0.931
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.193
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.662
	Confidence Interval	(2-Sided) 95.00% 0.397 to 1.103
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.255
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.465
	Confidence Interval	(2-Sided) 95.00% 0.286 to 0.756
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.243
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.525
	Confidence Interval	(2-Sided) 95.00% 0.295 to 0.935
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.287
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.952
	Confidence Interval	(2-Sided) 95.00% 0.768 to 1.180
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.107
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.965
	Confidence Interval	(2-Sided) 95.00% 0.733 to 1.269
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.137
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.992
	Confidence Interval	(2-Sided) 95.00% 0.710 to 1.387
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.168
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.913
	Confidence Interval	(2-Sided) 95.00% 0.649 to 1.285
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.171
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.660
	Confidence Interval	(2-Sided) 95.00% 0.415 to 1.051
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.233
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.690
	Confidence Interval	(2-Sided) 95.00% 0.445 to 1.072
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.220
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.724
	Confidence Interval	(2-Sided) 95.00% 0.423 to 1.239
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.268
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.950
	Confidence Interval	(2-Sided) 95.00% 0.789 to 1.144
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.093
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.985
	Confidence Interval	(2-Sided) 95.00% 0.777 to 1.249
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.119
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.067
	Confidence Interval	(2-Sided) 95.00% 0.797 to 1.428
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.146
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.922
	Confidence Interval	(2-Sided) 95.00% 0.686 to 1.239
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.148
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.866
	Confidence Interval	(2-Sided) 95.00% 0.583 to 1.287
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.198
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.649
	Confidence Interval	(2-Sided) 95.00% 0.444 to 0.950
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.190
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.722
	Confidence Interval	(2-Sided) 95.00% 0.457 to 1.140
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.228
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.897
	Confidence Interval	(2-Sided) 95.00% 0.748 to 1.075
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.091
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.887
	Confidence Interval	(2-Sided) 95.00% 0.703 to 1.119
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.116
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.846
	Confidence Interval	(2-Sided) 95.00% 0.638 to 1.123
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.142
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.812
	Confidence Interval	(2-Sided) 95.00% 0.609 to 1.084
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.145
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.580
	Confidence Interval	(2-Sided) 95.00% 0.394 to 0.855
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.194
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.439
	Confidence Interval	(2-Sided) 95.00% 0.301 to 0.639
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.188
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.451
	Confidence Interval	(2-Sided) 95.00% 0.285 to 0.714
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.230
	Estimation Comments

24. Secondary Outcome

Title	Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I
Description	Samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of soluble tumor necrosis factor receptors-I levels at these specified time points were reported.
Time Frame	6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

Outcome Measure Data

Analysis Population Description
PD Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	8	10	16	18
Time Since 1st Dose, 6 h	2457.23	2089.11	2240.84	2046.04	2267.35
Time Since 1st Dose, 12 h	2448.86	2624.12	2358.84	2151.51	1880.20
Time Since 1st Dose, 18 h	2371.29	2561.58	2175.30	2424.70	1958.95
Time Since 1st Dose, 24 h	2548.08	2423.76	2215.77	2420.75	1939.82
Time Since 1st Dose, 48 h	2466.18	2263.01	2814.63	2388.33	1925.54
Time Since 1st Dose, 72 h	2578.17	2609.42	2893.81	2386.32	1721.54
Time Since 1st Dose, 96 h	2436.04	2844.48	3591.89	2992.91	2094.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.850
	Confidence Interval	(2-Sided) 95.00% 0.646 to 1.119
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.137
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.072
	Confidence Interval	(2-Sided) 95.00% 0.814 to 1.411
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.138
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.080
	Confidence Interval	(2-Sided) 95.00% 0.790 to 1.478
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.157
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.951
	Confidence Interval	(2-Sided) 95.00% 0.715 to 1.266
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.143
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.918
	Confidence Interval	(2-Sided) 95.00% 0.655 to 1.285
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.168
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.012
	Confidence Interval	(2-Sided) 95.00% 0.735 to 1.395
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.160
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 1-SB-681323, 3 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.168
	Confidence Interval	(2-Sided) 95.00% 0.831 to 1.640
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.169
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.912
	Confidence Interval	(2-Sided) 95.00% 0.713 to 1.167
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.124
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.963
	Confidence Interval	(2-Sided) 95.00% 0.753 to 1.233
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.123
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.917
	Confidence Interval	(2-Sided) 95.00% 0.693 to 1.214
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.140
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.870
	Confidence Interval	(2-Sided) 95.00% 0.673 to 1.123
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.128
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.141
	Confidence Interval	(2-Sided) 95.00% 0.840 to 1.550
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.153
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.122
	Confidence Interval	(2-Sided) 95.00% 0.837 to 1.505
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.146
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 2-SB-681323, 7.5 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.474
	Confidence Interval	(2-Sided) 95.00% 1.063 to 2.045
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.164
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.833
	Confidence Interval	(2-Sided) 95.00% 0.672 to 1.031
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.107
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.879
	Confidence Interval	(2-Sided) 95.00% 0.707 to 1.092
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.109
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.023
	Confidence Interval	(2-Sided) 95.00% 0.800 to 1.307
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.123
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.950
	Confidence Interval	(2-Sided) 95.00% 0.761 to 1.187
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.111
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.968
	Confidence Interval	(2-Sided) 95.00% 0.743 to 1.262
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.132
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.926
	Confidence Interval	(2-Sided) 95.00% 0.718 to 1.193
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.127
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 3-SB-681323, 7.5 mg, 4 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	1.229
	Confidence Interval	(2-Sided) 95.00% 0.936 to 1.613
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.136
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 6 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.923
	Confidence Interval	(2-Sided) 95.00% 0.753 to 1.131
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.102
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 12 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.768
	Confidence Interval	(2-Sided) 95.00% 0.625 to 0.943
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.103
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 18 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95.00% 0.655 to 1.042
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.116
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 24 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.761
	Confidence Interval	(2-Sided) 95.00% 0.615 to 0.942
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.106
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 48 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.781
	Confidence Interval	(2-Sided) 95% 0.608 to 1.003
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.125
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 72 h post first dose
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.668
	Confidence Interval	(2-Sided) 95.00% 0.524 to 0.851
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.121
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Combined Placebo, Cohort 4-SB-681323, 10 mg, 24 h
	Comments	Comparison at 96 h post first dose
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Ratio (Treatment/Placebo)
	Estimated Value	0.860
	Confidence Interval	(2-Sided) 95.00% 0.659 to 1.122
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.133
	Estimation Comments

25. Secondary Outcome

Title	Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels
Description	Serum samples were collected at 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1. Mean absolute values of MPO levels at these specified time points were reported.
Time Frame	6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

Outcome Measure Data

Analysis Population Description
PD Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Combined Placebo	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	20	8	10	16	18
Time Since 1st Dose, 6 h	66792.4	56739.7	63552.3	44668.1	62108.1
Time Since 1st Dose, 12 h	94963.6	49535.7	85693.0	39467.3	61020.7
Time Since 1st Dose, 18 h	84143.5	70714.1	84578.5	64655.1	67290.8
Time Since 1st Dose, 24 h	104225.0	70943.1	112745.0	59336.2	71506.9
Time Since 1st Dose, 48 h	89181.9	47338.7	92324.6	53458.3	78699.2
Time Since 1st Dose, 72 h	79821.0	88493.3	148310.0	61893.0	73578.6
Time Since 1st Dose, 96 h	70263.5	108777.0	78570.3	84008.1	69268.3

26. Secondary Outcome

Title	Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24)
Description	Absolute values of the mean AUC 0-24 of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h10minutes [min], 24h45min, 27, 34, 40, 80 h since doing on Day 3).
Time Frame	For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) population was defined as patients in the 'All Subjects' population for whom a pharmacokinetic sample was obtained and analyzed. Note: Due to some placebo patients PK samples being assayed in error, the above PK population definition was adjusted to also exclude any patient receiving Placebo.

Arm/Group Title	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	9	12	18	18
Day 1	103.222	186.326	178.807	217.862
Day 2	112.199	207.050	182.590	237.549
Day 3	106.037	211.282	188.895	230.891

27. Secondary Outcome

Title	Mean Average Concentration (Cavg) of SB-681323
Description	Absolute values of mean Cavg of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3).
Time Frame	For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10minutes [min], 24h 45min, 27, 34, 40, 80 h since doing on Day 3)

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	9	12	18	18
Day 1	4.301	7.764	7.450	9.078
Day 2	4.675	8.627	7.608	9.898
Day 3	4.418	8.803	7.871	9.620

28. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of SB-681323
Description	Absolute values of the Cmax of SB-681323 were reported. PK samples were collected for cohort 1 and 3 at Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h) and for cohort 2 and 4 at Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3).
Time Frame	For cohort 1 and 3: Day 1 (pre-dose, 4, 4.25, 5, 6, 8, 12, 18h), Day 2 (pre-dose and 4h), Day 3 (0, 4, 24, 48h). For cohort 2 and 4: Day 1 (pre-dose), Day (pre-dose), Day 3 (pre-dose, 24h 10 min, 24h 45min, 27, 34, 40, 80 h since doing on Day 3)

Outcome Measure Data

Analysis Population Description
PK population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Cohort 1-SB-681323, 3 mg, 4 h	Cohort 2-SB-681323, 7.5 mg, 24 h	Cohort 3-SB-681323, 7.5 mg, 4 h	Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Measure Participants	9	11	18	17
Day 1	21.238	8.519	38.032	10.044
Day 2	22.830	8.842	38.697	10.382
Day 3	21.888	8.990	39.180	10.131

Adverse Events

	Combined Placebo		Cohort 1-SB-681323, 3 mg, 4 h		Cohort 2-SB-681323, 7.5 mg, 24 h		Cohort 3-SB-681323, 7.5 mg, 4 h		Cohort 4-SB-681323, 10 mg, 24 h
Time Frame	Up to follow up period (Day 7).
Adverse Event Reporting Description	All subjects population was used for collection of AEs.

Arm/Group Title	Combined Placebo		Cohort 1-SB-681323, 3 mg, 4 h		Cohort 2-SB-681323, 7.5 mg, 24 h		Cohort 3-SB-681323, 7.5 mg, 4 h		Cohort 4-SB-681323, 10 mg, 24 h
Arm/Group Description	Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days		Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days		Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days		Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days		Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Serious Adverse Events
	Combined Placebo		Cohort 1-SB-681323, 3 mg, 4 h		Cohort 2-SB-681323, 7.5 mg, 24 h		Cohort 3-SB-681323, 7.5 mg, 4 h		Cohort 4-SB-681323, 10 mg, 24 h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		1/9 (11.1%)		1/12 (8.3%)		4/18 (22.2%)		0/18 (0%)
Injury, poisoning and procedural complications
Gastrointestinal anastomotic leak	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Wound dehiscence	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Nervous system disorders
Mental impairment	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Quadriplegia	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Psychiatric disorders
Mental status changes	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Aspiration	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Combined Placebo		Cohort 1-SB-681323, 3 mg, 4 h		Cohort 2-SB-681323, 7.5 mg, 24 h		Cohort 3-SB-681323, 7.5 mg, 4 h		Cohort 4-SB-681323, 10 mg, 24 h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/20 (90%)		7/9 (77.8%)		10/12 (83.3%)		16/18 (88.9%)		14/18 (77.8%)
Blood and lymphatic system disorders
Anaemia	1/20 (5%)		1/9 (11.1%)		1/12 (8.3%)		1/18 (5.6%)		1/18 (5.6%)
Coagulopathy	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Leukopenia	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Cardiac disorders
Atrial fibrillation	0/20 (0%)		1/9 (11.1%)		1/12 (8.3%)		0/18 (0%)		1/18 (5.6%)
Tachycardia	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		1/18 (5.6%)
Bradycardia	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Cardiac failure	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Pericardial effusion	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Sinus tachycardia	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Supraventricular tachycardia	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Ventricular extrasystoles	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Gastrointestinal disorders
Nausea	6/20 (30%)		4/9 (44.4%)		4/12 (33.3%)		1/18 (5.6%)		3/18 (16.7%)
Constipation	4/20 (20%)		4/9 (44.4%)		0/12 (0%)		2/18 (11.1%)		1/18 (5.6%)
Vomiting	4/20 (20%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		1/18 (5.6%)
Ileus	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Dyspepsia	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
General disorders
Pyrexia	8/20 (40%)		1/9 (11.1%)		6/12 (50%)		4/18 (22.2%)		1/18 (5.6%)
Oedema peripheral	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Asthenia	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Infusion site bruising	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Infusion site extravasation	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Infections and infestations
Urinary tract infection	2/20 (10%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		1/18 (5.6%)
Pneumonia	0/20 (0%)		0/9 (0%)		0/12 (0%)		2/18 (11.1%)		0/18 (0%)
Bacteraemia	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Pneumococcal sepsis	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Pneumonia staphylococcal	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Injury, poisoning and procedural complications
Postoperative respiratory distress	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Investigations
Bacterial test positive	1/20 (5%)		1/9 (11.1%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Blood potassium decreased	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		2/18 (11.1%)
Hepatic enzyme increased	1/20 (5%)		1/9 (11.1%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Blood creatine phosphokinase increased	1/20 (5%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Blood pressure increased	0/20 (0%)		0/9 (0%)		0/12 (0%)		2/18 (11.1%)		0/18 (0%)
Haemoglobin decreased	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		1/18 (5.6%)
Blood alkaline phosphatase increased	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Blood glucose increased	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Blood phosphorus decreased	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Blood potassium increased	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Electrocardiogram QT prolonged	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Electrocardiogram ST segment depression	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Oxygen saturation decreased	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Prothrombin time prolonged	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Sputum culture positive	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Urine output decreased	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
White blood cell count increased	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Metabolism and nutrition disorders
Feeding disorder	4/20 (20%)		1/9 (11.1%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Hyperglycaemia	1/20 (5%)		0/9 (0%)		1/12 (8.3%)		4/18 (22.2%)		0/18 (0%)
Hypokalaemia	1/20 (5%)		2/9 (22.2%)		0/12 (0%)		1/18 (5.6%)		1/18 (5.6%)
Hypophosphataemia	0/20 (0%)		0/9 (0%)		2/12 (16.7%)		2/18 (11.1%)		0/18 (0%)
Hypovolaemia	2/20 (10%)		0/9 (0%)		2/12 (16.7%)		0/18 (0%)		0/18 (0%)
Hypomagnesaemia	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		1/18 (5.6%)		1/18 (5.6%)
Hypocalcaemia	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		2/18 (11.1%)
Hypoglycaemia	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		1/18 (5.6%)		0/18 (0%)
Hyponatraemia	1/20 (5%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Hypernatraemia	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Metabolic alkalosis	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Vitamin B complex deficiency	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Nervous system disorders
Hypoaesthesia	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		2/18 (11.1%)
Convulsion	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Headache	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Lethargy	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Paraesthesia	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Psychiatric disorders
Agitation	4/20 (20%)		0/9 (0%)		2/12 (16.7%)		2/18 (11.1%)		2/18 (11.1%)
Anxiety	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		0/18 (0%)		0/18 (0%)
Delirium	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Renal and urinary disorders
Oliguria	2/20 (10%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Renal failure acute	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		1/18 (5.6%)		0/18 (0%)
Urinary retention	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Myoglobinuria	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Urinary incontinence	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	2/20 (10%)		1/9 (11.1%)		0/12 (0%)		1/18 (5.6%)		1/18 (5.6%)
Hypoxia	0/20 (0%)		0/9 (0%)		1/12 (8.3%)		1/18 (5.6%)		1/18 (5.6%)
Respiratory failure	1/20 (5%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Acute respiratory distress syndrome	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Bronchial secretion retention	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Dyspnoea	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Haemoptysis	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Pleural effusion	0/20 (0%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Respiratory arrest	0/20 (0%)		1/9 (11.1%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Sinus congestion	1/20 (5%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)
Wheezing	0/20 (0%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		1/18 (5.6%)
Skin and subcutaneous tissue disorders
Pruritus	1/20 (5%)		1/9 (11.1%)		0/12 (0%)		1/18 (5.6%)		1/18 (5.6%)
Rash	1/20 (5%)		0/9 (0%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Vascular disorders
Hypertension	7/20 (35%)		2/9 (22.2%)		3/12 (25%)		3/18 (16.7%)		3/18 (16.7%)
Hypotension	3/20 (15%)		1/9 (11.1%)		0/12 (0%)		1/18 (5.6%)		0/18 (0%)
Deep vein thrombosis	2/20 (10%)		0/9 (0%)		0/12 (0%)		0/18 (0%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00996840

Other Study ID Numbers:

111592

First Posted:

Oct 16, 2009

Last Update Posted:

Oct 18, 2017

Last Verified:

Sep 1, 2017