Trial Outcomes & Findings for SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDS (NCT NCT00996840)

Last Updated: 2017-10-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

"Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Results posted on

2017-10-18

Participant Flow

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.

Seventy seven participants were randomized in the study and were included in All subject population.

Participant milestones

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

Reasons for withdrawal

Reasons for withdrawal
Measure	Combined Placebo Eligible participants received matching placebo intravenous (IV) infusion over 4 hours (h) or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h Eligible participants received SB-681323, 3 milligrams (mg), IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Overall Study Adverse Event	0	1	0	0	0
Overall Study Physician Decision	0	0	1	1	2
Overall Study Withdrawal by Subject	1	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=9 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=12 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days	Total n=77 Participants Total of all reporting groups
Age, Continuous	41.2 Years STANDARD_DEVIATION 17.70 • n=93 Participants	47.4 Years STANDARD_DEVIATION 19.31 • n=4 Participants	34.5 Years STANDARD_DEVIATION 15.61 • n=27 Participants	44.1 Years STANDARD_DEVIATION 15.89 • n=483 Participants	46.1 Years STANDARD_DEVIATION 21.80 • n=36 Participants	42.7 Years STANDARD_DEVIATION 18.24 • n=10 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	4 Participants n=483 Participants	5 Participants n=36 Participants	16 Participants n=10 Participants
Sex: Female, Male Male	17 Participants n=93 Participants	6 Participants n=4 Participants	11 Participants n=27 Participants	14 Participants n=483 Participants	13 Participants n=36 Participants	61 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	8 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	3 Participants n=483 Participants	4 Participants n=36 Participants	18 Participants n=10 Participants
Race (NIH/OMB) White	11 Participants n=93 Participants	9 Participants n=4 Participants	8 Participants n=27 Participants	12 Participants n=483 Participants	13 Participants n=36 Participants	53 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	1 Participants n=36 Participants	5 Participants n=10 Participants

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

Population: 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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: "Day 2, pre-dose", "Day 3, pre-dose", "Day 3, 24 h" and "Follow up (Day 7)"

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: Day 1 (pre-dose) and Day 3 (24 h)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=1 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=4 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Clinical Chemistry Parameters-estradiol	165.150 Picomole per liter Standard Deviation NA Only one participant was available at the time of analysis, dispersion could not be calculated.	210.108 Picomole per liter Standard Deviation 100.8360	—	—	—

PRIMARY outcome

Timeframe: Screening

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

Absolute values of Blood pH at screening were reported as clinical chemistry parameter.

Outcome measures

Outcome measures
Measure	Combined Placebo n=16 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=6 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=8 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=11 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=9 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Clinical Chemistry Parameters-Blood pH at Screening	7.358 pH Units Standard Deviation 0.0738	7.363 pH Units Standard Deviation 0.0824	7.358 pH Units Standard Deviation 0.0354	7.353 pH Units Standard Deviation 0.0297	7.373 pH Units Standard Deviation 0.0527

PRIMARY outcome

Timeframe: 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)"

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

Absolute values of SBP and DBP were reported.

Outcome measures

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

PRIMARY outcome

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

Absolute values of mean heart rate were reported.

Outcome measures

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

PRIMARY outcome

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

Absolute values of mean percent O2 in blood were reported.

Outcome measures

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

PRIMARY outcome

Timeframe: 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"

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

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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"

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

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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"

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

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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"

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

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 2, pre-dose, Day 3, pre-dose, Day 3, 24 h and Follow-up (Day 7)

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

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.

Outcome measures

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

PRIMARY outcome

Timeframe: Up to Follow-up (Day 7)

Population: All subject population.

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=9 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=12 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) Any AEs	18 Participants	7 Participants	10 Participants	16 Participants	14 Participants
Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) Any SAEs	1 Participants	1 Participants	1 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=8 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=10 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=16 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 6 h	509.44 Picogram per milliliter (pg/mL) Interval 404.31 to 641.92	286.17 Picogram per milliliter (pg/mL) Interval 193.56 to 423.09	391.09 Picogram per milliliter (pg/mL) Interval 285.5 to 535.73	309.57 Picogram per milliliter (pg/mL) Interval 241.39 to 397.0	395.09 Picogram per milliliter (pg/mL) Interval 311.51 to 501.11
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 12 h	516.49 Picogram per milliliter (pg/mL) Interval 386.08 to 690.93	315.89 Picogram per milliliter (pg/mL) Interval 195.6 to 510.16	362.03 Picogram per milliliter (pg/mL) Interval 242.29 to 540.95	348.23 Picogram per milliliter (pg/mL) Interval 252.52 to 480.21	310.98 Picogram per milliliter (pg/mL) Interval 229.12 to 422.08
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 18 h	476.94 Picogram per milliliter (pg/mL) Interval 342.58 to 663.98	247.22 Picogram per milliliter (pg/mL) Interval 143.35 to 426.37	275.7 Picogram per milliliter (pg/mL) Interval 174.63 to 435.27	292.24 Picogram per milliliter (pg/mL) Interval 202.25 to 422.28	238.7 Picogram per milliliter (pg/mL) Interval 167.94 to 339.28
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 24 h	556.06 Picogram per milliliter (pg/mL) Interval 396.84 to 779.16	231.1 Picogram per milliliter (pg/mL) Interval 132.58 to 402.84	228.1 Picogram per milliliter (pg/mL) Interval 143.19 to 363.33	310.47 Picogram per milliliter (pg/mL) Interval 214.22 to 449.97	162.82 Picogram per milliliter (pg/mL) Interval 111.89 to 236.94
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 48 h	324.35 Picogram per milliliter (pg/mL) Interval 227.93 to 461.57	167.69 Picogram per milliliter (pg/mL) Interval 93.79 to 299.85	290.59 Picogram per milliliter (pg/mL) Interval 175.53 to 481.08	235.13 Picogram per milliliter (pg/mL) Interval 158.44 to 348.94	119.98 Picogram per milliliter (pg/mL) Interval 75.81 to 189.87
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 72 h	250.21 Picogram per milliliter (pg/mL) Interval 162.45 to 385.39	165.46 Picogram per milliliter (pg/mL) Interval 82.36 to 332.41	184.93 Picogram per milliliter (pg/mL) Interval 100.25 to 341.14	182.54 Picogram per milliliter (pg/mL) Interval 113.18 to 294.4	106.32 Picogram per milliliter (pg/mL) Interval 62.32 to 181.39
Mean Serum Interleukin-6 Levels Time Since 1st Dose, 96 h	183.79 Picogram per milliliter (pg/mL) Interval 113.5 to 297.61	166.87 Picogram per milliliter (pg/mL) Interval 77.25 to 360.46	286.79 Picogram per milliliter (pg/mL) Interval 139.88 to 587.97	210.87 Picogram per milliliter (pg/mL) Interval 123.37 to 360.41	106.32 Picogram per milliliter (pg/mL) Interval 62.32 to 181.39

SECONDARY outcome

Timeframe: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

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

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=8 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=10 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=16 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 6 h	37.66 pg/ml Interval 29.86 to 47.5	18.22 pg/ml Interval 12.53 to 26.5	27.34 pg/ml Interval 19.88 to 37.6	21.06 pg/ml Interval 16.53 to 26.84	21.85 pg/ml Interval 17.38 to 27.46
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 12 h	26.53 pg/ml Interval 19.86 to 35.44	18.58 pg/ml Interval 11.42 to 30.21	21.00 pg/ml Interval 13.88 to 31.77	22.01 pg/ml Interval 16.0 to 30.29	17.42 pg/ml Interval 12.89 to 23.53
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 18 h	21.37 pg/ml Interval 15.61 to 29.26	14.55 pg/ml Interval 8.59 to 24.67	15.49 pg/ml Interval 9.88 to 24.28	21.10 pg/ml Interval 14.76 to 30.16	15.96 pg/ml Interval 11.57 to 22.04
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 24 h	24.05 pg/ml Interval 17.63 to 32.81	16.19 pg/ml Interval 9.61 to 27.28	15.75 pg/ml Interval 10.1 to 24.54	22.23 pg/ml Interval 15.79 to 31.29	15.79 pg/ml Interval 11.48 to 21.72
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 48 h	17.65 pg/ml Interval 12.3 to 25.33	16.24 pg/ml Interval 8.85 to 29.8	19.62 pg/ml Interval 11.55 to 33.32	21.70 pg/ml Interval 14.54 to 32.41	13.40 pg/ml Interval 9.19 to 19.53
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 72 h	15.99 pg/ml Interval 10.8 to 23.66	15.09 pg/ml Interval 7.91 to 28.75	17.19 pg/ml Interval 9.76 to 30.26	20.61 pg/ml Interval 13.36 to 31.77	15.47 pg/ml Interval 10.3 to 23.23
Mean Serum CXCL8 (Interleuin-8) Levels Time Since 1st Dose, 96 h	19.14 pg/ml Interval 13.65 to 26.84	17.33 pg/ml Interval 9.99 to 30.06	26.32 pg/ml Interval 15.58 to 44.47	33.54 pg/ml Interval 22.92 to 49.08	14.24 pg/ml Interval 9.81 to 20.65

SECONDARY outcome

Timeframe: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

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

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=8 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=10 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=16 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 96 h	171.67 mg/L Interval 126.16 to 233.62	90.20 mg/L Interval 55.5 to 146.58	124.33 mg/L Interval 80.24 to 192.64	123.97 mg/L Interval 88.87 to 172.95	77.40 mg/L Interval 55.46 to 108.01
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 48 h	159.36 mg/L Interval 122.11 to 207.97	105.45 mg/L Interval 68.22 to 162.98	105.17 mg/L Interval 71.94 to 153.77	138.05 mg/L Interval 103.11 to 184.84	92.50 mg/L Interval 70.13 to 122.02
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 72 h	179.03 mg/L Interval 138.38 to 231.62	83.21 mg/L Interval 55.09 to 125.67	123.58 mg/L Interval 86.64 to 176.27	116.27 mg/L Interval 88.06 to 153.52	78.55 mg/L Interval 60.09 to 102.69
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 6 h	123.62 mg/L Interval 108.9 to 140.33	95.60 mg/L Interval 77.82 to 117.45	117.68 mg/L Interval 99.05 to 139.82	117.42 mg/L Interval 102.48 to 134.55	110.88 mg/L Interval 97.49 to 126.1
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 12 h	138.02 mg/L Interval 117.47 to 162.17	109.74 mg/L Interval 84.28 to 142.88	133.17 mg/L Interval 106.76 to 166.11	136.01 mg/L Interval 114.22 to 161.96	122.42 mg/L Interval 103.71 to 144.52
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 18 h	144.10 mg/L Interval 118.34 to 175.45	112.06 mg/L Interval 81.18 to 154.69	142.96 mg/L Interval 109.14 to 187.25	153.76 mg/L Interval 123.93 to 190.78	121.97 mg/L Interval 99.71 to 149.2
Mean Serum C-Reactive Protein (CRP) Levels Time Since 1st Dose, 24 h	153.88 mg/L Interval 125.86 to 188.14	97.42 mg/L Interval 70.1 to 135.38	140.47 mg/L Interval 106.64 to 185.04	141.84 mg/L Interval 114.09 to 176.33	125.02 mg/L Interval 101.78 to 153.57

SECONDARY outcome

Timeframe: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

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

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=8 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=10 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=16 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 6 h	2457.23 pg/mL Interval 2129.05 to 2835.99	2089.11 pg/mL Interval 1653.81 to 2639.0	2240.84 pg/mL Interval 1829.96 to 2743.98	2046.04 pg/mL Interval 1748.13 to 2394.72	2267.35 pg/mL Interval 1961.1 to 2621.42
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 72 h	2578.17 pg/mL Interval 2180.51 to 3048.35	2609.42 pg/mL Interval 1987.3 to 3426.29	2893.81 pg/mL Interval 2268.96 to 3690.73	2386.32 pg/mL Interval 1977.8 to 2879.21	1721.54 pg/mL Interval 1445.26 to 2050.62
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 96 h	2436.04 pg/mL Interval 2035.38 to 2915.58	2844.48 pg/mL Interval 2133.36 to 3792.64	3591.89 pg/mL Interval 2729.54 to 4726.69	2992.91 pg/mL Interval 2441.71 to 3668.54	2094.76 pg/mL Interval 1720.42 to 2550.55
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 12 h	2448.86 pg/mL Interval 2124.1 to 2823.28	2624.12 pg/mL Interval 2074.37 to 3319.57	2358.84 pg/mL Interval 1923.3 to 2893.02	2151.51 pg/mL Interval 1829.23 to 2530.58	1880.20 pg/mL Interval 1620.96 to 2180.89
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 18 h	2371.29 pg/mL Interval 2016.83 to 2788.05	2561.58 pg/mL Interval 1960.37 to 3347.18	2175.30 pg/mL Interval 1725.14 to 2742.92	2424.70 pg/mL Interval 2020.77 to 2909.36	1958.95 pg/mL Interval 1659.12 to 2312.96
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 24 h	2548.08 pg/mL Interval 2198.02 to 2953.89	2423.76 pg/mL Interval 1898.68 to 3094.06	2215.77 pg/mL Interval 1793.02 to 2738.19	2420.75 pg/mL Interval 2053.68 to 2853.44	1939.82 pg/mL Interval 1664.47 to 2260.71
Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I Time Since 1st Dose, 48 h	2466.18 pg/mL Interval 2072.55 to 2934.58	2263.01 pg/mL Interval 1697.9 to 3016.21	2814.63 pg/mL Interval 2181.24 to 3631.93	2388.33 pg/mL Interval 1961.17 to 2908.52	1925.54 pg/mL Interval 1607.47 to 2306.54

SECONDARY outcome

Timeframe: 6, 12, 18, 24, 48, 72 and 96 h since first dose on Day 1

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

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.

Outcome measures

Outcome measures
Measure	Combined Placebo n=20 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=8 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=10 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=16 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 Participants Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 6 h	66792.4 pg/mL Interval 50163.43 to 88933.88	56739.7 pg/mL Interval 35517.01 to 90643.64	63552.3 pg/mL Interval 43761.86 to 92292.66	44668.1 pg/mL Interval 32839.83 to 60756.75	62108.1 pg/mL Interval 46378.91 to 83171.68
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 12 h	94963.6 pg/mL Interval 67732.71 to 133142.2	49535.7 pg/mL Interval 27600.02 to 88905.17	85693.0 pg/mL Interval 52298.94 to 140409.9	39467.3 pg/mL Interval 26518.49 to 58739.05	61020.7 pg/mL Interval 41912.35 to 88840.8
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 18 h	84143.5 pg/mL Interval 61847.22 to 114477.7	70714.1 pg/mL Interval 42068.42 to 118865.6	84578.5 pg/mL Interval 55836.68 to 128115.1	64655.1 pg/mL Interval 44897.15 to 93107.95	67290.8 pg/mL Interval 48679.72 to 93017.32
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 24 h	104225.0 pg/mL Interval 78979.78 to 137539.6	70943.1 pg/mL Interval 44906.34 to 112075.9	112745.0 pg/mL Interval 78188.58 to 162572.7	59336.2 pg/mL Interval 43636.15 to 80684.97	71506.9 pg/mL Interval 53769.8 to 95094.96
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 48 h	89181.9 pg/mL Interval 65657.74 to 121134.4	47338.7 pg/mL Interval 27813.57 to 80570.53	92324.6 pg/mL Interval 59313.52 to 143708.0	53458.3 pg/mL Interval 37505.36 to 76196.8	78699.2 pg/mL Interval 55978.77 to 110641.2
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 72 h	79821.0 pg/mL Interval 57835.74 to 110163.6	88493.3 pg/mL Interval 53136.78 to 147375.7	148310.0 pg/mL Interval 97377.15 to 225884.0	61893.0 pg/mL Interval 43541.25 to 87979.61	73578.6 pg/mL Interval 52720.51 to 102688.8
Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels Time Since 1st Dose, 96 h	70263.5 pg/mL Interval 50596.69 to 97574.74	108777.0 pg/mL Interval 62959.1 to 187936.9	78570.3 pg/mL Interval 47261.98 to 130618.7	84008.1 pg/mL Interval 55950.12 to 126136.8	69268.3 pg/mL Interval 46791.47 to 102542.1

SECONDARY outcome

Timeframe: 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)

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Combined Placebo n=9 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=12 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) Day 1	103.222 h*ng/mL Interval 85.306 to 124.902	186.326 h*ng/mL Interval 156.472 to 221.876	178.807 h*ng/mL Interval 153.644 to 208.09	217.862 h*ng/mL Interval 182.558 to 259.993	—
Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) Day 2	112.199 h*ng/mL Interval 92.339 to 136.331	207.050 h*ng/mL Interval 172.749 to 248.163	182.590 h*ng/mL Interval 156.946 to 212.425	237.549 h*ng/mL Interval 197.345 to 285.943	—
Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) Day 3	106.037 h*ng/mL Interval 81.444 to 138.057	211.282 h*ng/mL Interval 177.858 to 250.988	188.895 h*ng/mL Interval 160.977 to 221.654	230.891 h*ng/mL Interval 189.316 to 281.598	—

SECONDARY outcome

Timeframe: 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)

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

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).

Outcome measures

Outcome measures
Measure	Combined Placebo n=9 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=12 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Mean Average Concentration (Cavg) of SB-681323 Day 1	4.301 ng/mL Interval 3.554 to 5.204	7.764 ng/mL Interval 6.52 to 9.245	7.450 ng/mL Interval 6.402 to 8.67	9.078 ng/mL Interval 7.607 to 10.833	—
Mean Average Concentration (Cavg) of SB-681323 Day 2	4.675 ng/mL Interval 3.847 to 5.68	8.627 ng/mL Interval 7.198 to 10.34	7.608 ng/mL Interval 6.539 to 8.851	9.898 ng/mL Interval 8.223 to 11.914	—
Mean Average Concentration (Cavg) of SB-681323 Day 3	4.418 ng/mL Interval 3.393 to 5.752	8.803 ng/mL Interval 7.411 to 10.458	7.871 ng/mL Interval 6.707 to 9.236	9.620 ng/mL Interval 7.888 to 11.733	—

SECONDARY outcome

Timeframe: 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)

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

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).

Outcome measures

Outcome measures
Measure	Combined Placebo n=9 Participants Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=11 Participants Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=18 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=17 Participants Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Maximum Observed Concentration (Cmax) of SB-681323 Day 1	21.238 ng/mL Interval 18.235 to 24.736	8.519 ng/mL Interval 7.098 to 10.225	38.032 ng/mL Interval 33.317 to 43.415	10.044 ng/mL Interval 8.375 to 12.046	—
Maximum Observed Concentration (Cmax) of SB-681323 Day 2	22.830 ng/mL Interval 19.533 to 26.683	8.842 ng/mL Interval 7.377 to 10.599	38.697 ng/mL Interval 33.996 to 44.048	10.382 ng/mL Interval 8.647 to 12.466	—
Maximum Observed Concentration (Cmax) of SB-681323 Day 3	21.888 ng/mL Interval 18.67 to 25.661	8.990 ng/mL Interval 7.515 to 10.755	39.180 ng/mL Interval 34.157 to 44.943	10.131 ng/mL Interval 8.273 to 12.407	—

Adverse Events

Combined Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Cohort 1-SB-681323, 3 mg, 4 h

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort 2-SB-681323, 7.5 mg, 24 h

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Cohort 3-SB-681323, 7.5 mg, 4 h

Serious events: 4 serious events

Other events: 16 other events

Deaths: 0 deaths

Cohort 4-SB-681323, 10 mg, 24 h

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Combined Placebo n=20 participants at risk Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=9 participants at risk Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=12 participants at risk Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=18 participants at risk Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 participants at risk Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Injury, poisoning and procedural complications Gastrointestinal anastomotic leak	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Nervous system disorders Mental impairment	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Nervous system disorders Quadriplegia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Psychiatric disorders Mental status changes	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.

Other adverse events

Other adverse events
Measure	Combined Placebo n=20 participants at risk Eligible participants received matching placebo IV infusion over 4 h or 24 h for 3 days	Cohort 1-SB-681323, 3 mg, 4 h n=9 participants at risk Eligible participants received SB-681323, 3 mg, IV infusion over 4h for 3 days	Cohort 2-SB-681323, 7.5 mg, 24 h n=12 participants at risk Eligible participants received SB-681323, 7.5 mg, IV infusion over 24h for 3 days	Cohort 3-SB-681323, 7.5 mg, 4 h n=18 participants at risk Eligible participants received SB-681323, 7.5 mg, IV infusion over 4h for 3 days	Cohort 4-SB-681323, 10 mg, 24 h n=18 participants at risk Eligible participants received SB-681323, 10 mg, IV infusion over 24h for 3 days
Nervous system disorders Convulsion	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Nervous system disorders Headache	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Feeding disorder	20.0% 4/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hyperglycaemia	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	22.2% 4/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypokalaemia	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	22.2% 2/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	16.7% 2/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypovolaemia	10.0% 2/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	16.7% 2/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hyponatraemia	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Gastrointestinal disorders Nausea	30.0% 6/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	44.4% 4/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	33.3% 4/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	16.7% 3/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Gastrointestinal disorders Constipation	20.0% 4/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	44.4% 4/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Gastrointestinal disorders Vomiting	20.0% 4/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Gastrointestinal disorders Ileus	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Gastrointestinal disorders Dyspepsia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Infections and infestations Pneumococcal sepsis	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
General disorders Pyrexia	40.0% 8/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	50.0% 6/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	22.2% 4/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
General disorders Oedema peripheral	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
General disorders Asthenia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Infections and infestations Pneumonia staphylococcal	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
General disorders Infusion site bruising	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
General disorders Infusion site extravasation	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Vascular disorders Hypertension	35.0% 7/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	22.2% 2/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	25.0% 3/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	16.7% 3/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	16.7% 3/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Vascular disorders Hypotension	15.0% 3/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Vascular disorders Deep vein thrombosis	10.0% 2/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Bacterial test positive	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood potassium decreased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Hepatic enzyme increased	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood creatine phosphokinase increased	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood pressure increased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Skin and subcutaneous tissue disorders Pruritus	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Haemoglobin decreased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood alkaline phosphatase increased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood glucose increased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood phosphorus decreased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Skin and subcutaneous tissue disorders Rash	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Blood potassium increased	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Electrocardiogram QT prolonged	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Electrocardiogram ST segment depression	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Oxygen saturation decreased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Prothrombin time prolonged	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Sputum culture positive	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations Urine output decreased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Investigations White blood cell count increased	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	10.0% 2/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Bronchial secretion retention	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Psychiatric disorders Agitation	20.0% 4/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	16.7% 2/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Psychiatric disorders Anxiety	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Psychiatric disorders Delirium	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Atrial fibrillation	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Tachycardia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Nervous system disorders Hypoaesthesia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Bradycardia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Cardiac failure	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Pericardial effusion	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Sinus tachycardia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Supraventricular tachycardia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Cardiac disorders Ventricular extrasystoles	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Renal and urinary disorders Oliguria	10.0% 2/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Renal and urinary disorders Renal failure acute	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Renal and urinary disorders Urinary retention	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Renal and urinary disorders Myoglobinuria	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Renal and urinary disorders Urinary incontinence	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Blood and lymphatic system disorders Anaemia	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Blood and lymphatic system disorders Leukopenia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Infections and infestations Urinary tract infection	10.0% 2/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Infections and infestations Pneumonia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 2/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Infections and infestations Bacteraemia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Nervous system disorders Lethargy	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	11.1% 1/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Nervous system disorders Paraesthesia	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Injury, poisoning and procedural complications Postoperative respiratory distress	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Hypernatraemia	5.0% 1/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Metabolic alkalosis	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	5.6% 1/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.
Metabolism and nutrition disorders Vitamin B complex deficiency	0.00% 0/20 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/9 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	8.3% 1/12 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.	0.00% 0/18 • Up to follow up period (Day 7). All subjects population was used for collection of AEs.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER