Trial Outcomes & Findings for GSK2251052 in Complicated Urinary Tract Infection (NCT NCT01381549)

Last Updated: 2017-09-08

Results Overview

Clinical laboratory parameters included albumin and total protein. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in albumin and total protein are presented.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Results posted on

2017-09-08

Participant Flow

This study was conducted at eight centers in three countries (United States, Spain and Greece) from 28-June-2011 to 06-March-2012. A total of 20 participants were randomized in the study.

It was planned to enroll approximately 210 male and female participants with lower complicated urinary tract infection (cUTI) or pyelonephritis (complicated and uncomplicated); however, due to some unexpected microbiological findings, this study was terminated early with only 20 participants enrolled.

Participant milestones

Participant milestones
Measure	GSK2251052 750 mg Eligible participants received GSK2251052, 750 milligram (mg), in 200 or 250 millilitre (mL) saline solution as intravenous (IV) infusion administered over 60 minutes, twice a day (BID) and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Overall Study STARTED	6	8	6
Overall Study COMPLETED	6	8	5
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK2251052 750 mg Eligible participants received GSK2251052, 750 milligram (mg), in 200 or 250 millilitre (mL) saline solution as intravenous (IV) infusion administered over 60 minutes, twice a day (BID) and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Overall Study Ineligible: No organisms isolated	0	0	1

Baseline Characteristics

GSK2251052 in Complicated Urinary Tract Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.	Total n=20 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 13.60 • n=5 Participants	50.4 Years STANDARD_DEVIATION 24.45 • n=7 Participants	48.0 Years STANDARD_DEVIATION 17.48 • n=5 Participants	51.3 Years STANDARD_DEVIATION 18.95 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Population: Safety Population which comprised of all participants 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	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Albumin: Early Follow-up	8.2 Gram per Liter Standard Deviation 2.77	3.5 Gram per Liter Standard Deviation 3.39	3.4 Gram per Liter Standard Deviation 3.65
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Albumin: Late Follow-up	7.3 Gram per Liter Standard Deviation 4.93	3.5 Gram per Liter Standard Deviation 4.59	3.2 Gram per Liter Standard Deviation 3.77
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Total protein: Early Follow-up	9.4 Gram per Liter Standard Deviation 5.13	5.3 Gram per Liter Standard Deviation 3.27	6.4 Gram per Liter Standard Deviation 4.98
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Albumin: On IV therapy (Day 5)	-0.5 Gram per Liter Standard Deviation 4.85	-3.8 Gram per Liter Standard Deviation 7.09	-0.3 Gram per Liter Standard Deviation 3.06
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Albumin: On IV therapy (Day 11)	2.0 Gram per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Albumin: End of IV therapy	1.0 Gram per Liter Standard Deviation 4.69	-2.1 Gram per Liter Standard Deviation 7.38	0.8 Gram per Liter Standard Deviation 3.31
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Albumin: Test of Cure	5.7 Gram per Liter Standard Deviation 3.67	1.7 Gram per Liter Standard Deviation 5.79	2.6 Gram per Liter Standard Deviation 2.61
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Total protein: On IV therapy (Day 5)	0.0 Gram per Liter Standard Deviation 8.17	-5.0 Gram per Liter Standard Deviation 9.09	1.0 Gram per Liter Standard Deviation 6.24
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Total protein: On IV therapy (Day 11)	-5.0 Gram per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Total protein: End of IV therapy	-0.4 Gram per Liter Standard Deviation 9.76	-3.3 Gram per Liter Standard Deviation 10.14	3.0 Gram per Liter Standard Deviation 6.69
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Total protein: Test of Cure	5.8 Gram per Liter Standard Deviation 7.68	2.1 Gram per Liter Standard Deviation 6.89	6.4 Gram per Liter Standard Deviation 3.29
Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein Total protein: Late Follow-up	8.2 Gram per Liter Standard Deviation 4.92	5.3 Gram per Liter Standard Deviation 6.28	4.8 Gram per Liter Standard Deviation 5.40

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Clinical laboratory parameters included CCE. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in CCE are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE) CCE: Test of Cure	2.0 Milliliter per minute Standard Deviation NA Single participant	13.0 Milliliter per minute Standard Deviation NA Single participant	56.0 Milliliter per minute Standard Deviation NA Single participant
Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE) CCE: On IV therapy (Day 5)	—	18.0 Milliliter per minute Standard Deviation NA Single participant	—
Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE) CCE: Early Follow-up	1.0 Milliliter per minute Standard Deviation NA Single participant	21.0 Milliliter per minute Standard Deviation NA Single participant	60.0 Milliliter per minute Standard Deviation NA Single participant
Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE) CCE: Late Follow-up	25.0 Milliliter per minute Standard Deviation NA Single participant	21.0 Milliliter per minute Standard Deviation NA Single participant	—

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Clinical laboratory parameters included creatinine, direct bilirubin and total bilirubin. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in creatinine, direct bilirubin and total bilirubin are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Creatinine: Early Follow-up	-3.90 Micromole per liter Standard Deviation 6.134	2.88 Micromole per liter Standard Deviation 14.662	-4.56 Micromole per liter Standard Deviation 11.138
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: On IV therapy (Day 3)	-7.5 Micromole per liter Standard Deviation 10.73	-4.9 Micromole per liter Standard Deviation 4.45	-7.2 Micromole per liter Standard Deviation 6.42
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: On IV therapy (Day 5)	-7.0 Micromole per liter Standard Deviation 10.18	-3.5 Micromole per liter Standard Deviation 5.57	-7.3 Micromole per liter Standard Deviation 8.50
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Creatinine: On IV therapy (Day 5)	-4.20 Micromole per liter Standard Deviation 10.347	-5.78 Micromole per liter Standard Deviation 13.336	-11.97 Micromole per liter Standard Deviation 10.279
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Creatinine: On IV therapy (Day 11)	-1.50 Micromole per liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Creatinine: End of IV therapy	-0.24 Micromole per liter Standard Deviation 13.616	-11.26 Micromole per liter Standard Deviation 12.634	-8.70 Micromole per liter Standard Deviation 9.426
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Creatinine: Test of Cure	-2.17 Micromole per liter Standard Deviation 7.238	-9.66 Micromole per liter Standard Deviation 11.743	-8.54 Micromole per liter Standard Deviation 9.816
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Creatinine: Late Follow-up	4.43 Micromole per liter Standard Deviation 6.960	-5.22 Micromole per liter Standard Deviation 10.760	-5.22 Micromole per liter Standard Deviation 11.228
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: On IV therapy (Day 8)	-5.0 Micromole per liter Standard Deviation NA Single participant	-4.5 Micromole per liter Standard Deviation 0.71	-1.0 Micromole per liter Standard Deviation NA Single participant
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: On IV therapy (Day 11)	-1.0 Micromole per liter Standard Deviation NA Single particpant	—	—
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: End of IV therapy	-8.2 Micromole per liter Standard Deviation 11.37	-5.6 Micromole per liter Standard Deviation 0.71	-5.5 Micromole per liter Standard Deviation 6.16
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: Test of Cure	-7.7 Micromole per liter Standard Deviation 9.14	-4.7 Micromole per liter Standard Deviation 5.00	-6.4 Micromole per liter Standard Deviation 7.64
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: Early Follow-up	-6.2 Micromole per liter Standard Deviation 8.29	-4.5 Micromole per liter Standard Deviation 3.39	-6.0 Micromole per liter Standard Deviation 7.04
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin Total bilirubin: Late Follow-up	-5.2 Micromole per liter Standard Deviation 8.73	-4.8 Micromole per liter Standard Deviation 4.12	-5.0 Micromole per liter Standard Deviation 4.80

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Clinical laboratory parameters included C02 content/bicarbonate, chloride, glucose, potassium, sodium and urea/BUN. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in C02 content/bicarbonate, chloride, glucose, potassium, sodium and urea/BUN are presented.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Clinical laboratory parameters included ALT, ALP, AST, Creatine kinase and GGT. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in ALT, ALP, AST, Creatine kinase and GGT are presented.

Outcome measures

PRIMARY outcome

Timeframe: Up to 28 days post-therapy

Population: Safety Population.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	1 Participants	2 Participants	0 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	5 Participants	6 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to Late Follow-up Visit (21 to 28 days post-IV therapy)

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

Twelve lead ECGs were obtained during the study using an ECG machine that automatically measured PR, QRS, QT, and QT corrected by Bazett's formula (QTcB), QT corrected by Fridericia's formula (QTcF) intervals. Twelve lead ECGs were performed with the participant in a semi-supine position having rested in this position for at least 10 minutes beforehand. Measurements that deviated substantially from previous readings were repeated immediately. Three measurements were taken at pre-dose on Day 1 at least 5 min apart. One additional ECG measurement was taken after completion of the first infusion of study medication. Two ECG measurements (pre and post-1st infusion of the day) were taken on Day 4 while the participant was on IV therapy. When there was an abnormal finding, two more were taken and the mean PR interval, QRS duration, QT interval and QTcB were calculated from automated ECG readings. One ECG measurement was taken at the early safety follow-up visit.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 1: Pre-dose 1	0 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 1: Pre-dose 2	2 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 1: Pre-dose 3	1 Participants	2 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 1: Post-dose	1 Participants	5 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 4 (on IV treatment): Pre-dose	2 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Day 4 (on IV treatment): Post-dose	3 Participants	3 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Early Follow-up	0 Participants	3 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Withdrawal	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Vital sign measurements included SBP and DBP (supine or semi-supine). Measurements that deviated substantially from previous readings were repeated immediately. Mean SBP and DBP are presented.

Outcome measures

PRIMARY outcome

Timeframe: Up to Late Follow-up Visit (21 to 28 days post-IV therapy)

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

Vital sign measurements included heart rate. Measurements that deviated substantially from previous readings were repeated immediately. Mean heart rate is presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 9)	84.0 Beats per minute Standard Deviation NA Single participant	80.0 Beats per minute Standard Deviation NA Single participant	85.0 Beats per minute Standard Deviation NA Single participant
Summary of Vital Signs- Mean Heart Rate Baseline (Day 1)	85.8 Beats per minute Standard Deviation 10.63	99.3 Beats per minute Standard Deviation 13.78	87.7 Beats per minute Standard Deviation 11.78
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 2)	78.2 Beats per minute Standard Deviation 12.80	83.0 Beats per minute Standard Deviation 18.97	81.5 Beats per minute Standard Deviation 4.23
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 3)	77.8 Beats per minute Standard Deviation 4.92	80.6 Beats per minute Standard Deviation 14.79	81.4 Beats per minute Standard Deviation 9.40
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 4)	78.5 Beats per minute Standard Deviation 11.45	81.0 Beats per minute Standard Deviation 10.43	73.6 Beats per minute Standard Deviation 12.10
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 5)	72.3 Beats per minute Standard Deviation 13.52	80.3 Beats per minute Standard Deviation 10.55	68.2 Beats per minute Standard Deviation 11.45
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 6)	89.0 Beats per minute Standard Deviation NA Single participant	92.0 Beats per minute Standard Deviation 16.97	74.8 Beats per minute Standard Deviation 6.70
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 7)	81.0 Beats per minute Standard Deviation NA Single participant	88.5 Beats per minute Standard Deviation 16.26	78.3 Beats per minute Standard Deviation 9.07
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 8)	88.0 Beats per minute Standard Deviation NA Single participant	87.5 Beats per minute Standard Deviation 6.36	82.0 Beats per minute Standard Deviation NA Single participant
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 10)	91.0 Beats per minute Standard Deviation NA Single participant	—	86.0 Beats per minute Standard Deviation NA Single participant
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 11)	100.0 Beats per minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 12)	84.0 Beats per minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 13)	90.0 Beats per minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Heart Rate On IV therapy (Day 14)	92.0 Beats per minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Heart Rate End of IV therapy	72.8 Beats per minute Standard Deviation 11.82	82.8 Beats per minute Standard Deviation 8.91	71.0 Beats per minute Standard Deviation 7.32
Summary of Vital Signs- Mean Heart Rate Test of Cure	74.5 Beats per minute Standard Deviation 11.86	73.6 Beats per minute Standard Deviation 11.94	74.6 Beats per minute Standard Deviation 15.34
Summary of Vital Signs- Mean Heart Rate Early Follow-up	72.5 Beats per minute Standard Deviation 11.57	74.0 Beats per minute Standard Deviation 14.99	65.8 Beats per minute Standard Deviation 8.90
Summary of Vital Signs- Mean Heart Rate Late Follow-up	76.8 Beats per minute Standard Deviation 13.06	71.8 Beats per minute Standard Deviation 11.11	78.2 Beats per minute Standard Deviation 11.19

PRIMARY outcome

Timeframe: Up to Late Follow-up Visit (21 to 28 days post-IV therapy)

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

Vital sign measurements included respiratory rate. Measurements that deviated substantially from previous readings were repeated immediately. Mean respiration rate are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 6)	16.0 Breaths/minute Standard Deviation NA Single participant	17.0 Breaths/minute Standard Deviation 4.24	16.0 Breaths/minute Standard Deviation 4.32
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 7)	16.0 Breaths/minute Standard Deviation NA Single participant	16.5 Breaths/minute Standard Deviation 3.54	17.3 Breaths/minute Standard Deviation 4.16
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 8)	16.0 Breaths/minute Standard Deviation NA Single participant	15.0 Breaths/minute Standard Deviation 1.41	20.0 Breaths/minute Standard Deviation NA Single participant
Summary of Vital Signs- Mean Respiration Rate Late Follow-up	13.4 Breaths/minute Standard Deviation 1.95	16.0 Breaths/minute Standard Deviation 2.78	16.6 Breaths/minute Standard Deviation 3.71
Summary of Vital Signs- Mean Respiration Rate Baseline (Day 1)	17.3 Breaths/minute Standard Deviation 2.94	19.6 Breaths/minute Standard Deviation 3.85	17.3 Breaths/minute Standard Deviation 3.27
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 2)	15.0 Breaths/minute Standard Deviation 1.67	18.1 Breaths/minute Standard Deviation 3.68	16.8 Breaths/minute Standard Deviation 3.03
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 3)	14.2 Breaths/minute Standard Deviation 1.33	16.6 Breaths/minute Standard Deviation 3.62	16.8 Breaths/minute Standard Deviation 4.27
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 4)	15.5 Breaths/minute Standard Deviation 0.84	17.3 Breaths/minute Standard Deviation 3.99	17.8 Breaths/minute Standard Deviation 4.35
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 5)	14.5 Breaths/minute Standard Deviation 1.52	16.6 Breaths/minute Standard Deviation 3.46	18.8 Breaths/minute Standard Deviation 3.59
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 9)	14.0 Breaths/minute Standard Deviation NA Single participant	16.0 Breaths/minute Standard Deviation NA Single participant	22.0 Breaths/minute Standard Deviation NA Single participant
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 10)	17.0 Breaths/minute Standard Deviation NA Single participant	—	20.0 Breaths/minute Standard Deviation NA Single participant
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 11)	15.0 Breaths/minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 12)	16.0 Breaths/minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 13)	14.0 Breaths/minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Respiration Rate On IV therapy (Day 14)	14.0 Breaths/minute Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Respiration Rate End of IV therapy	16.0 Breaths/minute Standard Deviation 2.45	15.8 Breaths/minute Standard Deviation 2.96	16.4 Breaths/minute Standard Deviation 2.19
Summary of Vital Signs- Mean Respiration Rate Test of Cure	14.0 Breaths/minute Standard Deviation 1.79	15.5 Breaths/minute Standard Deviation 3.42	18.2 Breaths/minute Standard Deviation 4.15
Summary of Vital Signs- Mean Respiration Rate Early Follow-up	15.3 Breaths/minute Standard Deviation 1.97	15.9 Breaths/minute Standard Deviation 3.52	16.4 Breaths/minute Standard Deviation 3.21

PRIMARY outcome

Timeframe: Up to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Vital sign measurements included temperature (oral, tympanic or rectal). Measurements that deviated substantially from previous readings were repeated immediately. Temperature was assessed as normal hospital practice dictated and the maximum daily temperature was recorded in the electronic case report form (eCRF).

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Summary of Vital Signs- Mean Temperature On IV therapy (Day 3)	36.75 Celsius Standard Deviation 0.706	36.79 Celsius Standard Deviation 0.380	37.74 Celsius Standard Deviation 0.817
Summary of Vital Signs- Mean Temperature Baseline (Day 1)	38.08 Celsius Standard Deviation 0.741	38.41 Celsius Standard Deviation 0.946	38.30 Celsius Standard Deviation 0.469
Summary of Vital Signs- Mean Temperature On IV therapy (Day 2)	36.97 Celsius Standard Deviation 1.063	37.30 Celsius Standard Deviation 0.693	37.30 Celsius Standard Deviation 0.860
Summary of Vital Signs- Mean Temperature On IV therapy (Day 4)	36.60 Celsius Standard Deviation 0.469	36.71 Celsius Standard Deviation 0.669	37.38 Celsius Standard Deviation 0.986
Summary of Vital Signs- Mean Temperature On IV therapy (Day 5)	36.27 Celsius Standard Deviation 0.378	36.59 Celsius Standard Deviation 0.498	36.96 Celsius Standard Deviation 0.654
Summary of Vital Signs- Mean Temperature On IV therapy (Day 6)	37.00 Celsius Standard Deviation NA Single participant	36.90 Celsius Standard Deviation 1.273	36.40 Celsius Standard Deviation 0.283
Summary of Vital Signs- Mean Temperature On IV therapy (Day 7)	36.20 Celsius Standard Deviation NA Single participant	36.95 Celsius Standard Deviation 0.778	36.93 Celsius Standard Deviation 0.416
Summary of Vital Signs- Mean Temperature On IV therapy (Day 8)	36.80 Celsius Standard Deviation NA Single participant	36.80 Celsius Standard Deviation 0.707	36.50 Celsius Standard Deviation NA Single participant
Summary of Vital Signs- Mean Temperature On IV therapy (Day 9)	36.50 Celsius Standard Deviation NA Single participant	36.80 Celsius Standard Deviation NA Single participant	36.50 Celsius Standard Deviation NA Single participant
Summary of Vital Signs- Mean Temperature On IV therapy (Day 10)	37.00 Celsius Standard Deviation NA Single participant	—	36.50 Celsius Standard Deviation NA Single participant
Summary of Vital Signs- Mean Temperature On IV therapy (Day 11)	37.00 Celsius Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Temperature On IV therapy (Day 12)	36.80 Celsius Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Temperature On IV therapy (Day 13)	36.20 Celsius Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Temperature On IV therapy (Day 14)	36.80 Celsius Standard Deviation NA Single participant	—	—
Summary of Vital Signs- Mean Temperature End of IV therapy	36.18 Celsius Standard Deviation 0.512	36.75 Celsius Standard Deviation 0.676	36.38 Celsius Standard Deviation 0.299
Summary of Vital Signs- Mean Temperature Test of Cure	36.25 Celsius Standard Deviation 0.418	35.98 Celsius Standard Deviation 0.709	36.14 Celsius Standard Deviation 0.744
Summary of Vital Signs- Mean Temperature Early Follow-up	36.23 Celsius Standard Deviation 0.427	35.99 Celsius Standard Deviation 0.387	36.28 Celsius Standard Deviation 0.606
Summary of Vital Signs- Mean Temperature Late Follow-up	36.40 Celsius Standard Deviation 0.110	36.08 Celsius Standard Deviation 0.512	36.00 Celsius Standard Deviation 0.394

PRIMARY outcome

Timeframe: Test of Cure Visit (5 to 9 days post-IV therapy)

Population: Microbiological Intent to Treat (MITT) comprised of all randomized participants who received at least one dose of study medication and had at least one gram-negative uropathogen and no more than two gram-negative uropathogens (≥10\^5 Colony forming units \[CFU\]/mL for each pathogen) identified from Baseline urine culture.

The therapeutic response was the combination of a participant's clinical and microbiological response. It was assessed at the Test of Cure visit in participants who have a qualifying Gram-negative uropathogen at Baseline and have had a minimum of 5 days of IV therapy. Therapeutic response was a measure of the overall efficacy response, and a therapeutic success referred to participants who have been deemed both a 'clinical success' and a 'microbiological success'. All other combinations (other than 'clinical success' + 'microbiological success') were deemed failures for therapeutic response.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=5 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Therapeutic Response at the Test of Cure Visit Therapeutic Success	1 Participants	5 Participants	1 Participants
Therapeutic Response at the Test of Cure Visit Therapeutic Failure	5 Participants	3 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Hematology parameters included hematocrit. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in hematocrit are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Hematology Parameters- Hematocrit End of IV therapy	-0.0140 Fraction Standard Deviation 0.06893	-0.0155 Fraction Standard Deviation 0.06930	-0.0120 Fraction Standard Deviation 0.02993
Change From Baseline in Hematology Parameters- Hematocrit Late Follow-up	0.0373 Fraction Standard Deviation 0.03079	-0.0007 Fraction Standard Deviation 0.03322	-0.0038 Fraction Standard Deviation 0.01669

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Hematology parameters included MCH. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in MCH are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH) End of IV therapy	-0.60 Picograms Standard Deviation 0.748	-0.60 Picograms Standard Deviation 0.668	-0.07 Picograms Standard Deviation 0.628
Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH) Late Follow-up	-0.85 Picograms Standard Deviation 0.657	-0.89 Picograms Standard Deviation 0.573	-0.14 Picograms Standard Deviation 0.472

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Hematology parameters included MCV. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in MCV are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV) End of IV therapy	-3.0 Femtoliters Standard Deviation 2.45	-1.3 Femtoliters Standard Deviation 1.98	-1.0 Femtoliters Standard Deviation 0.89
Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV) Late Follow-up	-2.2 Femtoliters Standard Deviation 0.98	-1.3 Femtoliters Standard Deviation 2.75	-0.8 Femtoliters Standard Deviation 1.79

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Hematology parameters included RBC count and reticulocytes. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in RBC count and reticulocytes are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes RBC: Late Follow-up	0.52 Trillion cells per liter Standard Deviation 0.366	0.07 Trillion cells per liter Standard Deviation 0.236	0.02 Trillion cells per liter Standard Deviation 0.228
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes RBC: End of IV therapy	-0.10 Trillion cells per liter Standard Deviation 0.689	-0.10 Trillion cells per liter Standard Deviation 0.707	-0.08 Trillion cells per liter Standard Deviation 0.360
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes Reticulocytes: End of IV therapy	-0.0331 Trillion cells per liter Standard Deviation 0.04544	-0.0312 Trillion cells per liter Standard Deviation 0.02489	-0.0072 Trillion cells per liter Standard Deviation 0.02295
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes Reticulocytes: Late Follow-up	-0.0466 Trillion cells per liter Standard Deviation 0.09881	-0.0092 Trillion cells per liter Standard Deviation 0.03267	0.0080 Trillion cells per liter Standard Deviation 0.02577

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Hematology parameters included hemoglobin and MCHC. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in hemoglobin and MCHC are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC: End of IV therapy	4.0 Gram per Liter Standard Deviation 3.81	-1.8 Gram per Liter Standard Deviation 6.50	4.2 Gram per Liter Standard Deviation 6.74
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC: Late Follow-up	-3.0 Gram per Liter Standard Deviation 8.44	-5.0 Gram per Liter Standard Deviation 5.94	1.8 Gram per Liter Standard Deviation 8.29
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin: Late Follow-up	11.0 Gram per Liter Standard Deviation 7.24	-2.1 Gram per Liter Standard Deviation 9.67	-0.6 Gram per Liter Standard Deviation 4.16
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin: End of IV therapy	-3.0 Gram per Liter Standard Deviation 22.77	-5.5 Gram per Liter Standard Deviation 21.36	-2.5 Gram per Liter Standard Deviation 8.17

PRIMARY outcome

Timeframe: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

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

Hematology parameters included basophils, eosinophils, lymphocytes, monocytes, platelet count, total neutrophils and WBC. Baseline was Day 1. Change from Baseline was calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Late follow-up visit in basophils, eosinophils, lymphocytes, monocytes, platelet count, total neutrophils and WBC are presented.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Eosinophils: Late Follow-up	0.093 Gigacells per Liter Standard Deviation 0.1488	0.067 Gigacells per Liter Standard Deviation 0.0966	0.086 Gigacells per Liter Standard Deviation 0.0385
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Lymphocytes: End of IV therapy	0.580 Gigacells per Liter Standard Deviation 1.2076	0.514 Gigacells per Liter Standard Deviation 0.3816	0.596 Gigacells per Liter Standard Deviation 0.5140
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Monocytes: End of IV therapy	-0.188 Gigacells per Liter Standard Deviation 0.3739	-0.256 Gigacells per Liter Standard Deviation 0.2015	-0.442 Gigacells per Liter Standard Deviation 0.3841
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Platelet count: Late Follow-up	48.8 Gigacells per Liter Standard Deviation 129.10	45.4 Gigacells per Liter Standard Deviation 34.93	39.8 Gigacells per Liter Standard Deviation 35.81
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Total neutrophils: End of IV therapy	-8.178 Gigacells per Liter Standard Deviation 3.6642	-6.695 Gigacells per Liter Standard Deviation 4.6214	-4.656 Gigacells per Liter Standard Deviation 6.6652
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) WBC count: End of IV therapy	-7.48 Gigacells per Liter Standard Deviation 4.242	-6.30 Gigacells per Liter Standard Deviation 4.607	-4.36 Gigacells per Liter Standard Deviation 6.696
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) WBC count: Late Follow-up	-6.33 Gigacells per Liter Standard Deviation 4.918	-7.11 Gigacells per Liter Standard Deviation 6.207	-7.54 Gigacells per Liter Standard Deviation 8.486
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Basophils: End of IV therapy	0.028 Gigacells per Liter Standard Deviation 0.0084	0.018 Gigacells per Liter Standard Deviation 0.0116	0.014 Gigacells per Liter Standard Deviation 0.0182
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Basophils: Late Follow-up	0.022 Gigacells per Liter Standard Deviation 0.0147	0.020 Gigacells per Liter Standard Deviation 0.0163	0.016 Gigacells per Liter Standard Deviation 0.0114
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Eosinophils: End of IV therapy	0.274 Gigacells per Liter Standard Deviation 0.1389	0.096 Gigacells per Liter Standard Deviation 0.0980	0.090 Gigacells per Liter Standard Deviation 0.0682
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Lymphocytes: Late Follow-up	0.687 Gigacells per Liter Standard Deviation 1.5191	0.774 Gigacells per Liter Standard Deviation 0.4808	0.436 Gigacells per Liter Standard Deviation 0.7578
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Monocytes: Late Follow-up	-0.380 Gigacells per Liter Standard Deviation 0.4553	-0.230 Gigacells per Liter Standard Deviation 0.3902	-0.186 Gigacells per Liter Standard Deviation 0.2103
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Platelet count: End of IV therapy	141.0 Gigacells per Liter Standard Deviation 171.58	83.2 Gigacells per Liter Standard Deviation 139.06	105.4 Gigacells per Liter Standard Deviation 92.20
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) Total neutrophils: Late Follow-up	-6.765 Gigacells per Liter Standard Deviation 4.0488	-7.737 Gigacells per Liter Standard Deviation 6.3494	-7.902 Gigacells per Liter Standard Deviation 8.1795

SECONDARY outcome

Timeframe: End of IV therapy (0-24 hours post-therapy), Test of Cure Visit (5 to 9 days post-IV therapy) and Late Follow-up (21-28 days post-therapy)

Population: MITT Population.

Microbiological response involved both microbiological success and microbiological failure. A reduction in the uropathogens in the urine culture and no growth on blood culture was termed as microbiological success. Increase in the uropathogens in the urine culture and pathogens identified in the blood culture or use of antibacterials other than study treatments were classified as microbiological failures.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=5 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Test of Cure · Microbiological Failure	5 Participants	3 Participants	4 Participants
Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Late Folllow-up · Microbiological Failure	4 Participants	2 Participants	4 Participants
Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit End of IV therapy · Microbiological Success	3 Participants	5 Participants	5 Participants
Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit End of IV therapy · Microbiological Failure	3 Participants	3 Participants	0 Participants
Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Test of Cure · Microbiological Success	1 Participants	5 Participants	1 Participants
Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Late Folllow-up · Microbiological Success	2 Participants	6 Participants	1 Participants

SECONDARY outcome

Timeframe: End of IV therapy (0-24 hours post-therapy), Test of Cure Visit (5 to 9 days post-IV therapy) and Late Follow-up (21-28 days post-therapy)

Population: MITT Population.

Clinical response was a combination of clinical success and clinical failure. In clinical success, participants showed no signs and symptoms of pyelonephritis and lower complicated urinary tract infection and antibiotics are not used for the same. In clinical failure, there is reappearance of signs and symptoms of and lower complicated urinary tract infection and participant required antibiotics for the same.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=5 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit End of IV therapy · Clinical Success	4 Participants	6 Participants	5 Participants
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit End of IV therapy · Clinical Failure	2 Participants	2 Participants	0 Participants
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Test of Cure · Clinical Success	4 Participants	6 Participants	4 Participants
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Test of Cure · Clinical Failure	2 Participants	2 Participants	1 Participants
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Late Follow-up · Clinical Success	3 Participants	6 Participants	2 Participants
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit Late Follow-up · Clinical Failure	3 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)

Population: MITT Population.

Outcome measures

Outcome measures
Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=5 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit Late Follow-up · Therapeutic Failure	4 Participants	2 Participants	4 Participants
Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit End of IV therapy · Therapeutic Success	3 Participants	5 Participants	5 Participants
Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit End of IV therapy · Therapeutic Failure	3 Participants	3 Participants	0 Participants
Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit Late Follow-up · Therapeutic Success	2 Participants	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 3: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 3: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 3: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 4: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 4: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 4: Pre- dose (just prior to the start of the first infusion of the day) and 1 hour (just prior to the end of the infusion), 2, 4, and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 4: Pre-dose (just prior to the start of the first infusion of the day) 0.5, 1 hour (just prior to the end of the infusion), 1.25, 1.5, 2, 3, 4, 8 and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 4: Pre-dose (just prior to the start of the first infusion of the day) 0.5, 1 hour (just prior to the end of the infusion), 1.25, 1.5, 2, 3, 4, 8 and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 4: Pre-dose (just prior to the start of the first infusion of the day) 0.5, 1 hour (just prior to the end of the infusion), 1.25, 1.5, 2, 3, 4, 8 and 12 hours post-dose

The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.

Outcome measures

Outcome data not reported

Adverse Events

GSK2251052 750 mg

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

GSK2251052 1500 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Imipenem-Cilastatin

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK2251052 750 mg n=6 participants at risk Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, twice a day (BID) and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 participants at risk Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 participants at risk Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Investigations Aspiration bronchial	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Investigations Haemoglobin decreased	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Cardiac disorders Cardiac arrest	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Infections and infestations Escherichia bacteraemia	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.

Other adverse events

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

Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Glucose: On IV therapy (Day 5)	0.42 Millimole per Liter Standard Deviation 1.993	2.25 Millimole per Liter Standard Deviation 1.700	-2.00 Millimole per Liter Standard Deviation 2.685
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Potassium: Test of Cure	0.78 Millimole per Liter Standard Deviation 0.739	0.40 Millimole per Liter Standard Deviation 0.526	0.44 Millimole per Liter Standard Deviation 0.351
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Sodium: On IV therapy (Day 5)	1.2 Millimole per Liter Standard Deviation 2.23	0.3 Millimole per Liter Standard Deviation 2.75	2.3 Millimole per Liter Standard Deviation 2.52
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Urea/BUN: End of IV therapy	-0.30 Millimole per Liter Standard Deviation 2.633	-1.13 Millimole per Liter Standard Deviation 1.367	-0.57 Millimole per Liter Standard Deviation 1.046
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Calcium: On IV therapy (Day 5)	0.082 Millimole per Liter Standard Deviation 0.1664	-0.112 Millimole per Liter Standard Deviation 0.2170	0.060 Millimole per Liter Standard Deviation 0.1229
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Calcium: On IV therapy (Day 11)	0.030 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Calcium: End of IV therapy	-0.020 Millimole per Liter Standard Deviation 0.2411	0.071 Millimole per Liter Standard Deviation 0.1964	0.078 Millimole per Liter Standard Deviation 0.0930
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Calcium: Test of Cure	0.235 Millimole per Liter Standard Deviation 0.2627	0.096 Millimole per Liter Standard Deviation 0.2057	0.128 Millimole per Liter Standard Deviation 0.1114
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Calcium: Early Follow-up	0.276 Millimole per Liter Standard Deviation 0.1383	0.120 Millimole per Liter Standard Deviation 0.0919	0.142 Millimole per Liter Standard Deviation 0.1232
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Calcium: Late Follow-up	0.243 Millimole per Liter Standard Deviation 0.0922	0.115 Millimole per Liter Standard Deviation 0.1027	0.110 Millimole per Liter Standard Deviation 0.1538
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) C02 content/Bicarbonate: On IV therapy (Day 5)	-1.7 Millimole per Liter Standard Deviation 3.01	0.0 Millimole per Liter Standard Deviation 2.83	-2.0 Millimole per Liter Standard Deviation 0.00
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) C02 content/Bicarbonate: On IV therapy (Day 11)	-3.0 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) C02 content/Bicarbonate: End of IV therapy	-2.4 Millimole per Liter Standard Deviation 2.07	0.6 Millimole per Liter Standard Deviation 2.30	-0.3 Millimole per Liter Standard Deviation 2.88
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) C02 content/Bicarbonate: Test of Cure	-0.8 Millimole per Liter Standard Deviation 1.72	2.7 Millimole per Liter Standard Deviation 1.80	1.4 Millimole per Liter Standard Deviation 4.28
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) C02 content/Bicarbonate: Early Follow-up	0.0 Millimole per Liter Standard Deviation 3.81	0.3 Millimole per Liter Standard Deviation 1.63	-0.4 Millimole per Liter Standard Deviation 4.72
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) C02 content/Bicarbonate: Late Follow-up	0.7 Millimole per Liter Standard Deviation 2.34	1.8 Millimole per Liter Standard Deviation 2.71	1.2 Millimole per Liter Standard Deviation 4.97
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Chloride: On IV therapy (Day 5)	1.2 Millimole per Liter Standard Deviation 4.07	1.8 Millimole per Liter Standard Deviation 3.50	3.7 Millimole per Liter Standard Deviation 1.15
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Chloride: On IV therapy (Day 11)	4.0 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Chloride: End of IV therapy	1.0 Millimole per Liter Standard Deviation 3.74	3.0 Millimole per Liter Standard Deviation 3.83	-0.2 Millimole per Liter Standard Deviation 2.32
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Chloride: Test of Cure	0.5 Millimole per Liter Standard Deviation 3.94	1.0 Millimole per Liter Standard Deviation 3.83	0.2 Millimole per Liter Standard Deviation 2.28
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Chloride: Early Follow-up	0.6 Millimole per Liter Standard Deviation 4.72	0.5 Millimole per Liter Standard Deviation 4.51	0.0 Millimole per Liter Standard Deviation 2.35
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Chloride: Late Follow-up	0.3 Millimole per Liter Standard Deviation 4.18	-0.5 Millimole per Liter Standard Deviation 3.02	2.2 Millimole per Liter Standard Deviation 0.84
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Glucose: On IV therapy (Day 11)	1.50 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Glucose: End of IV therapy	-1.06 Millimole per Liter Standard Deviation 1.372	1.09 Millimole per Liter Standard Deviation 1.542	-0.68 Millimole per Liter Standard Deviation 2.741
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Glucose: Test of Cure	-0.35 Millimole per Liter Standard Deviation 1.649	-0.11 Millimole per Liter Standard Deviation 1.173	-0.24 Millimole per Liter Standard Deviation 2.261
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Glucose: Early Follow-up	-0.80 Millimole per Liter Standard Deviation 1.158	0.07 Millimole per Liter Standard Deviation 1.316	-0.78 Millimole per Liter Standard Deviation 1.949
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Glucose: Late Follow-up	-0.45 Millimole per Liter Standard Deviation 1.106	0.58 Millimole per Liter Standard Deviation 1.703	-0.56 Millimole per Liter Standard Deviation 2.395
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Potassium: On IV therapy (Day 5)	0.52 Millimole per Liter Standard Deviation 0.662	-0.05 Millimole per Liter Standard Deviation 0.645	0.37 Millimole per Liter Standard Deviation 0.666
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Potassium: On IV therapy (Day 11)	0.00 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Potassium: End of IV therapy	0.46 Millimole per Liter Standard Deviation 0.623	0.24 Millimole per Liter Standard Deviation 0.509	0.48 Millimole per Liter Standard Deviation 0.407
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Potassium: Early Follow-up	0.40 Millimole per Liter Standard Deviation 0.725	0.50 Millimole per Liter Standard Deviation 0.400	0.42 Millimole per Liter Standard Deviation 0.327
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Potassium: Late Follow-up	0.28 Millimole per Liter Standard Deviation 0.471	0.53 Millimole per Liter Standard Deviation 0.547	0.40 Millimole per Liter Standard Deviation 0.495
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Sodium: On IV therapy (Day 11)	4.0 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Sodium: End of IV therapy	0.4 Millimole per Liter Standard Deviation 2.79	1.7 Millimole per Liter Standard Deviation 3.15	-0.8 Millimole per Liter Standard Deviation 2.14
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Sodium: Test of Cure	1.8 Millimole per Liter Standard Deviation 1.33	1.3 Millimole per Liter Standard Deviation 3.40	1.0 Millimole per Liter Standard Deviation 1.73
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Sodium: Early Follow-up	1.8 Millimole per Liter Standard Deviation 3.27	-0.5 Millimole per Liter Standard Deviation 3.45	1.0 Millimole per Liter Standard Deviation 1.58
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Sodium: Late Follow-up	1.2 Millimole per Liter Standard Deviation 3.54	-1.2 Millimole per Liter Standard Deviation 4.36	2.0 Millimole per Liter Standard Deviation 2.65
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Urea/BUN: On IV therapy (Day 5)	-0.98 Millimole per Liter Standard Deviation 2.024	-0.45 Millimole per Liter Standard Deviation 1.515	-0.97 Millimole per Liter Standard Deviation 0.874
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Urea/BUN: On IV therapy (Day 11)	-2.50 Millimole per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Urea/BUN: Test of Cure	-0.38 Millimole per Liter Standard Deviation 1.184	-0.73 Millimole per Liter Standard Deviation 1.456	-0.38 Millimole per Liter Standard Deviation 1.033
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Urea/BUN: Early Follow-up	-0.64 Millimole per Liter Standard Deviation 1.305	0.20 Millimole per Liter Standard Deviation 2.262	-0.34 Millimole per Liter Standard Deviation 0.853
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) Urea/BUN: Late Follow-up	-0.30 Millimole per Liter Standard Deviation 0.716	-0.33 Millimole per Liter Standard Deviation 1.199	-0.12 Millimole per Liter Standard Deviation 1.932

Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: On IV therapy (Day 3)	5.0 International units per Liter Standard Deviation 12.07	4.1 International units per Liter Standard Deviation 12.58	19.2 International units per Liter Standard Deviation 16.04
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: On IV therapy (Day 5)	31.5 International units per Liter Standard Deviation 57.16	6.3 International units per Liter Standard Deviation 13.38	20.0 International units per Liter Standard Deviation 34.66
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: On IV therapy (Day 8)	-2.0 International units per Liter Standard Deviation NA Single participant	2.0 International units per Liter Standard Deviation 0.00	2.0 International units per Liter Standard Deviation NA Single participant
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: On IV therapy (Day 11)	2.0 International units per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: End of IV therapy	22.0 International units per Liter Standard Deviation 34.71	13.1 International units per Liter Standard Deviation 15.08	15.7 International units per Liter Standard Deviation 23.34
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: Test of Cure	1.5 International units per Liter Standard Deviation 9.81	-2.3 International units per Liter Standard Deviation 4.54	-1.4 International units per Liter Standard Deviation 6.50
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: Early Follow-up	-1.2 International units per Liter Standard Deviation 8.56	-4.8 International units per Liter Standard Deviation 10.34	1.2 International units per Liter Standard Deviation 6.76
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) AST: Late Follow-up	3.3 International units per Liter Standard Deviation 15.02	-3.3 International units per Liter Standard Deviation 10.07	3.4 International units per Liter Standard Deviation 2.88
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) Creatine kinase : On IV therapy (Day 5)	-76.0 International units per Liter Standard Deviation 118.58	-37.8 International units per Liter Standard Deviation 46.94	-26.0 International units per Liter Standard Deviation 18.33
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) Creatine kinase : End of IV therapy	-36.0 International units per Liter Standard Deviation 33.56	-165.6 International units per Liter Standard Deviation 407.70	-23.7 International units per Liter Standard Deviation 18.33
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) Creatine kinase : Test of Cure	-65.3 International units per Liter Standard Deviation 129.24	-156.4 International units per Liter Standard Deviation 420.00	18.4 International units per Liter Standard Deviation 18.80
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) Creatine kinase : Late Follow-up	-37.8 International units per Liter Standard Deviation 134.80	-168.8 International units per Liter Standard Deviation 448.90	0.2 International units per Liter Standard Deviation 41.05
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) GGT : On IV therapy (Day 5)	41.7 International units per Liter Standard Deviation 49.61	6.5 International units per Liter Standard Deviation 8.27	24.0 International units per Liter Standard Deviation 35.68
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) GGT : On IV therapy (Day 11)	22.0 International units per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) GGT : End of IV therapy	35.8 International units per Liter Standard Deviation 49.96	28.9 International units per Liter Standard Deviation 39.88	14.0 International units per Liter Standard Deviation 20.27
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) GGT : Test of Cure	16.5 International units per Liter Standard Deviation 20.67	23.3 International units per Liter Standard Deviation 24.69	3.6 International units per Liter Standard Deviation 8.76
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) GGT : Early Follow-up	-1.4 International units per Liter Standard Deviation 36.90	8.3 International units per Liter Standard Deviation 13.54	-0.8 International units per Liter Standard Deviation 12.15
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) GGT : Late Follow-up	-16.7 International units per Liter Standard Deviation 54.70	1.3 International units per Liter Standard Deviation 9.58	-3.8 International units per Liter Standard Deviation 12.03
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) Creatine kinase : On IV therapy (Day 11)	4.0 International units per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) Creatine kinase : Early Follow-up	-41.4 International units per Liter Standard Deviation 158.04	-218.2 International units per Liter Standard Deviation 495.53	-6.0 International units per Liter Standard Deviation 30.12
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: Early Follow-up	7.4 International units per Liter Standard Deviation 21.01	1.2 International units per Liter Standard Deviation 23.73	8.2 International units per Liter Standard Deviation 12.01
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: Late Follow-up	5.7 International units per Liter Standard Deviation 20.64	2.3 International units per Liter Standard Deviation 13.81	3.6 International units per Liter Standard Deviation 13.13
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: On IV therapy (Day 3)	5.7 International units per Liter Standard Deviation 8.14	10.4 International units per Liter Standard Deviation 21.53	12.8 International units per Liter Standard Deviation 11.19
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: On IV therapy (Day 5)	33.2 International units per Liter Standard Deviation 46.82	4.8 International units per Liter Standard Deviation 8.85	13.3 International units per Liter Standard Deviation 17.90
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: On IV therapy (Day 8)	4.0 International units per Liter Standard Deviation NA Single participant	1.5 International units per Liter Standard Deviation 6.36	-3.0 International units per Liter Standard Deviation NA Single participant
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: On IV therapy (Day 11)	2.0 International units per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: End of IV therapy	35.4 International units per Liter Standard Deviation 40.46	18.6 International units per Liter Standard Deviation 21.35	21.3 International units per Liter Standard Deviation 29.30
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: Test of Cure	17.5 International units per Liter Standard Deviation 18.53	7.3 International units per Liter Standard Deviation 10.34	7.0 International units per Liter Standard Deviation 10.12
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: Early Follow-up	4.8 International units per Liter Standard Deviation 5.97	1.0 International units per Liter Standard Deviation 5.33	5.8 International units per Liter Standard Deviation 7.40
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALT: Late Follow-up	3.3 International units per Liter Standard Deviation 5.99	-0.3 International units per Liter Standard Deviation 4.32	4.2 International units per Liter Standard Deviation 5.50
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: On IV therapy (Day 3)	10.8 International units per Liter Standard Deviation 26.33	14.3 International units per Liter Standard Deviation 30.12	13.2 International units per Liter Standard Deviation 28.28
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: On IV therapy (Day 5)	11.2 International units per Liter Standard Deviation 22.99	4.0 International units per Liter Standard Deviation 27.14	17.7 International units per Liter Standard Deviation 35.50
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: On IV therapy (Day 8)	-10.0 International units per Liter Standard Deviation NA Single participant	21.5 International units per Liter Standard Deviation 12.02	-10.0 International units per Liter Standard Deviation NA Single participant
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: On IV therapy (Day 11)	-11.0 International units per Liter Standard Deviation NA Single participant	—	—
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: End of IV therapy	7.4 International units per Liter Standard Deviation 26.28	16.3 International units per Liter Standard Deviation 34.62	10.2 International units per Liter Standard Deviation 22.60
Change From Baseline in Clinical Laboratory Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase and Gamma Glutamyl Transferase (GGT) ALP: Test of Cure	10.8 International units per Liter Standard Deviation 23.47	6.9 International units per Liter Standard Deviation 15.04	14.8 International units per Liter Standard Deviation 17.01

Measure	GSK2251052 750 mg n=6 Participants Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 Participants Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 Participants Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Baseline (Day 1)	129.7 Millimeters of mercury (mmHg) Standard Deviation 29.27	131.9 Millimeters of mercury (mmHg) Standard Deviation 14.56	120.0 Millimeters of mercury (mmHg) Standard Deviation 17.64
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 2)	131.2 Millimeters of mercury (mmHg) Standard Deviation 15.20	125.4 Millimeters of mercury (mmHg) Standard Deviation 15.89	120.0 Millimeters of mercury (mmHg) Standard Deviation 19.75
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 3)	123.8 Millimeters of mercury (mmHg) Standard Deviation 15.09	126.6 Millimeters of mercury (mmHg) Standard Deviation 28.69	123.8 Millimeters of mercury (mmHg) Standard Deviation 13.88
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 4)	137.8 Millimeters of mercury (mmHg) Standard Deviation 17.61	127.0 Millimeters of mercury (mmHg) Standard Deviation 30.79	124.2 Millimeters of mercury (mmHg) Standard Deviation 17.98
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 5)	135.2 Millimeters of mercury (mmHg) Standard Deviation 27.58	126.6 Millimeters of mercury (mmHg) Standard Deviation 35.10	116.8 Millimeters of mercury (mmHg) Standard Deviation 18.42
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 6)	150.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	125.5 Millimeters of mercury (mmHg) Standard Deviation 34.65	115.0 Millimeters of mercury (mmHg) Standard Deviation 12.25
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 7)	165.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	125.0 Millimeters of mercury (mmHg) Standard Deviation 21.21	116.7 Millimeters of mercury (mmHg) Standard Deviation 20.82
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 8)	170.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	125.0 Millimeters of mercury (mmHg) Standard Deviation 49.50	110.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: End of IV therapy	130.0 Millimeters of mercury (mmHg) Standard Deviation 17.03	116.1 Millimeters of mercury (mmHg) Standard Deviation 13.93	117.5 Millimeters of mercury (mmHg) Standard Deviation 11.73
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Test of Cure	131.3 Millimeters of mercury (mmHg) Standard Deviation 5.85	126.9 Millimeters of mercury (mmHg) Standard Deviation 27.17	126.4 Millimeters of mercury (mmHg) Standard Deviation 20.12
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Late Follow-up	148.0 Millimeters of mercury (mmHg) Standard Deviation 23.64	117.6 Millimeters of mercury (mmHg) Standard Deviation 21.77	116.6 Millimeters of mercury (mmHg) Standard Deviation 13.35
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Baseline (Day 1)	68.0 Millimeters of mercury (mmHg) Standard Deviation 12.84	77.3 Millimeters of mercury (mmHg) Standard Deviation 9.25	66.5 Millimeters of mercury (mmHg) Standard Deviation 4.64
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 3)	77.2 Millimeters of mercury (mmHg) Standard Deviation 12.22	72.1 Millimeters of mercury (mmHg) Standard Deviation 15.72	71.2 Millimeters of mercury (mmHg) Standard Deviation 3.56
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 4)	85.5 Millimeters of mercury (mmHg) Standard Deviation 15.73	79.5 Millimeters of mercury (mmHg) Standard Deviation 19.41	69.6 Millimeters of mercury (mmHg) Standard Deviation 5.77
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: End of IV therapy	74.0 Millimeters of mercury (mmHg) Standard Deviation 9.94	69.4 Millimeters of mercury (mmHg) Standard Deviation 17.22	71.5 Millimeters of mercury (mmHg) Standard Deviation 12.42
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Test of Cure	82.2 Millimeters of mercury (mmHg) Standard Deviation 5.88	70.6 Millimeters of mercury (mmHg) Standard Deviation 12.47	71.8 Millimeters of mercury (mmHg) Standard Deviation 15.14
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 9)	161.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	130.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	105.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 10)	140.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	110.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 11)	155.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 12)	140.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 13)	130.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: On IV therapy (Day 14)	152.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP: Early Follow-up	128.0 Millimeters of mercury (mmHg) Standard Deviation 17.03	120.1 Millimeters of mercury (mmHg) Standard Deviation 15.24	123.8 Millimeters of mercury (mmHg) Standard Deviation 13.10
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 2)	78.3 Millimeters of mercury (mmHg) Standard Deviation 12.82	69.0 Millimeters of mercury (mmHg) Standard Deviation 15.61	70.3 Millimeters of mercury (mmHg) Standard Deviation 10.78
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 5)	83.8 Millimeters of mercury (mmHg) Standard Deviation 13.95	79.7 Millimeters of mercury (mmHg) Standard Deviation 21.89	67.0 Millimeters of mercury (mmHg) Standard Deviation 4.12
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 6)	90.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	81.0 Millimeters of mercury (mmHg) Standard Deviation 12.73	72.5 Millimeters of mercury (mmHg) Standard Deviation 15.00
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 7)	85.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	70.0 Millimeters of mercury (mmHg) Standard Deviation 0.00	67.7 Millimeters of mercury (mmHg) Standard Deviation 9.29
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 8)	90.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	69.0 Millimeters of mercury (mmHg) Standard Deviation 15.56	70.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 9)	95.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	80.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	65.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 10)	69.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	70.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 11)	69.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 12)	75.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 13)	80.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: On IV therapy (Day 14)	69.0 Millimeters of mercury (mmHg) Standard Deviation NA Single participant	—	—
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Early Follow-up	73.8 Millimeters of mercury (mmHg) Standard Deviation 9.62	72.0 Millimeters of mercury (mmHg) Standard Deviation 11.72	68.8 Millimeters of mercury (mmHg) Standard Deviation 12.05
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP: Late Follow-up	87.7 Millimeters of mercury (mmHg) Standard Deviation 16.18	67.5 Millimeters of mercury (mmHg) Standard Deviation 16.13	65.0 Millimeters of mercury (mmHg) Standard Deviation 5.29

Measure	GSK2251052 750 mg n=6 participants at risk Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, twice a day (BID) and Imipenem-cilastatin matching placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	GSK2251052 1500 mg n=8 participants at risk Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and Imipenem-cilastatin placebo solution, 100 mL, administered over 20 to 30 minutes, four times daily from Day 2 to Day 14 of the study.	Imipenem-Cilastatin n=6 participants at risk Eligible participants received Imipenem-cilastatin 500 mg in 100 mL saline solution as IV infusion administered over 20 to 30 minutes four times daily and two doses of GSK2251052 matching placebo saline solution, 200 or 250 mL, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
Gastrointestinal disorders Nausea	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	25.0% 2/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Nervous system disorders Dizziness	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	33.3% 2/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Nervous system disorders Headache	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	33.3% 2/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Nervous system disorders Paraesthesia	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Infections and infestations Pharyngitis	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Infections and infestations Oral herpes	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Infections and infestations Vulvovaginal candidiasis	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Investigations Alanine aminotransferase increased	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	25.0% 2/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Investigations Haemoglobin decreased	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Vascular disorders Phlebitis	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Vascular disorders Deep vein thrombosis	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
General disorders Chest pain	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
General disorders Papillitis	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Eye disorders Eyelid oedema	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	12.5% 1/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Psychiatric disorders Depression	16.7% 1/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/8 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.	0.00% 0/6 • Up to 28 days post-therapy SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.