GSK2251052 in Complicated Urinary Tract Infection

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01381549
• Collaborator: (none)
• Enrollment: 20
• Locations: 24
• Arms: 3
• Actual Duration (Months): 8.3
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is being conducted to evaluate the safety, efficacy (clinical and microbiological), pharmacokinetics/pharmacodynamics of GSK2251052 and to assess whether it would be a suitable antibiotic for the treatment for febrile lower cUTI and pyelonephritis(complicated and uncomplicated). GSK2251052 will be compared to imipenem-cilastatin, which is an antibiotic commonly used to treat serious cUTI infections. GSK2251052 has a spectrum of microbiological activity that includes pathogens responsible for cUTI.

Condition or Disease	Intervention/Treatment	Phase
Infections, Urinary Tract	Drug: GSK2251052; Drug: imipenem-cilastatin; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Dose-finding, Multicenter Study of the Safety, Tolerability, and Efficacy of GSK2251052 Therapy Compared to Imipenem-cilastatin in the Treatment of Adult Subjects With Febrile Complicated Lower Urinary Tract Infections and Acute Pyelonephritis
• Actual Study Start Date: Jun 28, 2011
• Actual Primary Completion Date: Mar 6, 2012
• Actual Study Completion Date: Mar 6, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK2251052 750mg q12h administered via IV infusion, plus saline placebo	Drug: GSK2251052; Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion; Other: Placebo; saline placebo
Experimental: GSK2251052 1500mg q12h administered via IV infusion, plus saline placebo	Drug: GSK2251052; Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion; Other: Placebo; saline placebo
Active Comparator: imipenem-cilastatin 500 mg imipenem monohydrate and 500 mg cilastatin sodium; q6h administered via IV infusion, plus saline placebo	Drug: imipenem-cilastatin; Prepare as per prescribing information instructions in 100 mL bag of 0.9% NaCl and administered via IV infusion; Other Names: Primaxin® (Manufacturer: Merck) ; Other: Placebo; saline placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

   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.

2. Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE) [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

   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.

3. Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

   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.

4. Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN) [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

   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.

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

   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.

6. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Up to 28 days post-therapy]

   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.

7. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Up to Late Follow-up Visit (21 to 28 days post-IV therapy)]

   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.

8. Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Up to Late Follow up Visit (21 to 28 days post-IV therapy)]

   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.

9. Summary of Vital Signs- Mean Heart Rate [Up to Late Follow-up Visit (21 to 28 days post-IV therapy)]

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

10. Summary of Vital Signs- Mean Respiration Rate [Up to Late Follow-up Visit (21 to 28 days post-IV therapy)]

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

11. Summary of Vital Signs- Mean Temperature [Up to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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).

12. Therapeutic Response at the Test of Cure Visit [Test of Cure Visit (5 to 9 days post-IV therapy)]

    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.

13. Change From Baseline in Hematology Parameters- Hematocrit [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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.

14. Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH) [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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.

15. Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV) [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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.

16. Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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.

17. Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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.

18. Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC) [Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)]

    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.

Secondary Outcome Measures

1. Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit [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)]

   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.

2. Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit [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)]

   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.

3. Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit [End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)]

   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.

4. Maximum Plasma Concentration (Cmax) of GSK2251052 [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.

5. Area Under the Concentration Time Curve (AUC) of GSK2251052 [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.

6. Time to Cmax (Tmax) of GSK2251052 [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.

7. Cmax of GSK2251052 Using Non-intensive PK Sampling [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.

8. AUC of GSK2251052 Using Non-intensive PK Sampling [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.

9. Tmax of GSK2251052 Using Non-intensive PK Sampling [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.

10. Cmax of GSK2251052 Using Intensive PK Sampling [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.

11. AUC of GSK2251052 Using Intensive PK Sampling [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.

12. Tmax of GSK2251052 Using Intensive PK Sampling [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult subjects least 18 years of age.

N.B. Females of non-childbearing or childbearing potential may be enrolled. Females of childbearing potential must have a negative pregnancy test at study entry and must have practiced adequate contraception for at least 30 days prior to study entry. Additionally, the subject agrees to one of the following methods for avoidance of pregnancy during the entire study treatment period:

• Abstinence; or,

• Oral Contraceptive, either combined estrogen/progesterone or progesterone alone, PLUS an additional barrier method [ie, condom, occlusive cap (diaphragm or cervical/vault caps) or vaginal spermicidal agent (foam/gel/film/cream/suppository)]; or,

• Injectable progesterone; or

• Implants of levonorgestrel; or,

• Estrogenic vaginal ring; or,

• Percutaneous contraceptive patches; or

• Intrauterine device (IUD) or intrauterine system (IUS) showing that failure rate is less than 1% in the IUD or IUS product label; or,

• Has a male partner who is sterilized (vasectomy with documentation of azoospermia).

• Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

• Females are considered to be of non-childbearing potential if they have documented tubal ligation or hysterectomy; or are postmenopausal, defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]

• Subject requires hospitalisation and has clinical signs and symptoms of lower cUTI or pyelonephritis (complicated or uncomplicated) as defined below, that requires parenteral treatment only with a treatment course of a minimum of 5 days and a maximum of 14 days:

• Lower cUTI - subjects must have documented fever defined as >38°C oral, >38.5°C tympanic or >39°C rectal, within the last 24 hours exceptions would be:

• Afebrile subjects with lower cUTI who have a white blood cell count (WBC) ≥15,000 cells/mm3

• Afebrile subjects with a lower cUTI following requiring parenteral therapy due to a specific indication e.g. before and during an operative procedure, when oral antibiotics are not indicated or in cases where the cUTI is suspected to be due to a pathogen resistant to current oral antibiotics

• and at least two of the following UTI symptoms including dysuria, frequency, urgency or suprapubic pain, with the presence of a complicating factor:

• Male gender;

• Current bladder instrumentation or indwelling urinary catheter that has to be removed two days before the end of IV study drug administration;

• Obstructive uropathy that is expected to be medically or surgically treated during the course of IV study drug administration;

• Urogenital surgery within 7 days preceding administration of the first dose of study drug;

• Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder with voiding disturbance of at least 100 mL residual urine.

• Acute pyelonephritis (complicated or uncomplicated): subjects must have documented fever defined as >38°C oral, >38.5°C tympanic or >39°C rectal, within the last 24 hours and flank pain or costovertebral angle tenderness (CVA). Complicating factors for pyelonephritis are the same as for complicated UTI.

• Subject has pyuria (white blood cell [WBC] count > 10/µL (or >5/high-power field [HPF] in a conventional urinalysis) in unspun clean-catch midstream urine (MSU) or catheter urine sample or >= 10 WBC/HPF in spun MSU or catheter urine).

• Subject has Gram-negative organism(s) on direct examination of a Gram-stained specimen from unspun or spun MSU or catheter urine sample.

• Subject has provided a pre-therapy urine specimen obtained within 48 hours prior to the start of therapy, which when cultured has grown at least one and not more than two Gram-negative uropathogens at >=10^5 CFU/mL.

• A subject may be enrolled before the results of the pre-therapy urine culture is known, but the subject should be withdrawn from the study if the culture does not yield at least one but not more than two qualifying Gram-negative uropathogens at

=10^5 CFU/mL or if the culture yields Gram-positive uropathogens.

• A subject with lower cUTI or pyelonephritis (complicated or uncomplicated) who has failed a previous antibacterial treatment regimen is eligible provided a urine specimen is positive for one and not more than two bacterial Gram-negative uropathogens at >=10^5 CFU/mL. Subjects who are treatment failures due to imipenem-cilastatin should not be enrolled.

• QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block

• Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

• Concomitant infection requiring systemic antibacterial therapy other than study drugs at the time of randomisation.

• Subject is known to have one or more of the following:

• A urinary catheter that is not being removed during the study (or with an expectation that a catheter would be inserted during therapy with study drug and subsequently not removed during the study period; (intermittent straight catheterisation is acceptable)

• Complete permanent obstruction of the urinary tract;

• A permanent indwelling catheter or comparable instrumentation including nephrostomy that will not be removed during IV study drug administration

• Suspected or confirmed prostatitis

• Suspected or confirmed perinephric or intrarenal abscess

• A UTI suspected or confirmed to be fungal in origin (with >= 10^3 fungal CFU/mL)

• A UTI suspected or confirmed to be due to a Gram-positive uropathogen(s), with >= 10^5 Gram-positive organism CFU/mL;

• A UTI known at study entry to be caused by a pathogen(s) resistant to the study antimicrobial agent;

• Known ileal loops or vesico-ureteral reflux ;

• Polycystic kidney disease.

• Subject has an APACHE II score >20

• Subject has known severe impairment of renal function including: a calculated creatinine clearance (CrCl) of less than 50 mL/min; requirement for peritoneal dialysis, haemodialysis, or haemofiltration; oliguria (less than 20 mL urine output per hour over 24 hours);

• Subject with an intractable lower cUTI requiring more than 14 Days IV treatment.

• Subjects with asymptomatic lower cUTI, such as subjects with spinal cord injury with lower cUTI who are not able to perceive symptoms due to their injury.

• Subject with lower cUTI or pyelonephritis (complicated and uncomplicated) who has received any amount of a potentially therapeutic antibiotic within the 96 h before providing the baseline urine culture specimen or prior to the start of the study.

• Subject has Gram-positive organism(s) on direct examination of a Gram-stained specimen of spun/unspun MSU or catheter urine.

• Subject is considered unlikely to survive the 4 6 week study period or has any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure or septic shock).

• Subject has evidence of known or pre-existing severe hepatic disease (Child-Pugh score of B or C).

• Subject has a known baseline haemoglobin less than 10 g/dL ,haematocrit less than 30% and/or a known reticulocyte count of >5% (i.e., reticulocytes >5% of total RBC mass)

• Subject has known neutropenia or is anticipated to develop neutropenia during the course of the study (i.e., new chemotherapy subject), with absolute neutrophil count less than 1000 cells/mm3

• Subject has a known platelet count less than 75,000 cells /mm3 (subjects with platelet counts as low as 50,000 cells /mm3 are eligible if the reduction is historically stable).

• Subject has an immunocompromising illness; including known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), organ (including bone marrow) transplantation, hematological malignancy, and/or immunosuppressive therapy , including high-dose corticosteroids (e.g., greater than 40 mg prednisone or equivalent per day for greater than two weeks)

• Subject has participated in any investigational drug or device study within 30 days of study entry or within 5 half-lives, whichever is longer.

• Subject has previously received treatment with GSK2251052.

• Subject has a prior history of seizures or has a CNS abnormality predisposing them to seizures or has a lowered seizure threshold and/or is using concomitant medications with seizure potential.

• Subject requires probenicid or valproic acid medications.

• Subject has a history of moderate or severe hypersensitivity to beta-lactam antibiotics.

• Subject is pregnant or nursing

• Subject, in the opinion of the investigator may be significantly compromised by a potential drop in haemoglobin ≥2.5g/dl which is not related to the condition under study

• French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Los Angeles	California	United States	90033
2	GSK Investigational Site	Council Bluffs	Iowa	United States	51503
3	GSK Investigational Site	Topeka	Kansas	United States	66604
4	GSK Investigational Site	Corsicana	Texas	United States	75110
5	GSK Investigational Site	Chicoutimi	Quebec	Canada	G7H 5H6
6	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 5N4
7	GSK Investigational Site	Suresnes		France	92151
8	GSK Investigational Site	Toulouse cedex 9		France	31059
9	GSK Investigational Site	Athens		Greece	11527
10	GSK Investigational Site	Chaidari		Greece	12462
11	GSK Investigational Site	Goudi, Athens		Greece	11527
12	GSK Investigational Site	Thessaloniki		Greece	56429
13	GSK Investigational Site	Irkutsk		Russian Federation	664079
14	GSK Investigational Site	Moscow		Russian Federation	125367
15	GSK Investigational Site	Rostov-on-Don		Russian Federation	344022
16	GSK Investigational Site	Smolensk		Russian Federation	214018
17	GSK Investigational Site	St'Petersburg		Russian Federation	194354
18	GSK Investigational Site	Alicante		Spain	03010
19	GSK Investigational Site	Elche (Alicante)		Spain	03203
20	GSK Investigational Site	Getafe/Madrid		Spain	28905
21	GSK Investigational Site	Granada		Spain	18003
22	GSK Investigational Site	Madrid		Spain	28040
23	GSK Investigational Site	Murcia		Spain
24	GSK Investigational Site	Pama de Mallorca		Spain	07010

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01381549
• Other Study ID Numbers: 114688
• First Posted: Jun 27, 2011
• Last Update Posted: Sep 8, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by GlaxoSmithKline: Gram-negative; uropathogens; complicated lower urinary tract infection; pyelonephritis
• Additional relevant MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; Imipenem; Cilastatin, Imipenem Drug Combination; Cilastatin

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	6	8	6
COMPLETED	6	8	5
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin	Total
Arm/Group Description	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.	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.	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 of all reporting groups
Overall Participants	6	8	6	20
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.7 (13.60)	50.4 (24.45)	48.0 (17.48)	51.3 (18.95)
Sex: Female, Male (Count of Participants)
Female	3 50%	4 50%	3 50%	10 50%
Male	3 50%	4 50%	3 50%	10 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 12.5%	1 16.7%	2 10%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 12.5%	0 0%	1 5%
White	6 100%	6 75%	5 83.3%	17 85%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Albumin: On IV therapy (Day 5)	-0.5 (4.85)	-3.8 (7.09)	-0.3 (3.06)
Albumin: On IV therapy (Day 11)	2.0 (NA)
Albumin: End of IV therapy	1.0 (4.69)	-2.1 (7.38)	0.8 (3.31)
Albumin: Test of Cure	5.7 (3.67)	1.7 (5.79)	2.6 (2.61)
Albumin: Early Follow-up	8.2 (2.77)	3.5 (3.39)	3.4 (3.65)
Albumin: Late Follow-up	7.3 (4.93)	3.5 (4.59)	3.2 (3.77)
Total protein: On IV therapy (Day 5)	0.0 (8.17)	-5.0 (9.09)	1.0 (6.24)
Total protein: On IV therapy (Day 11)	-5.0 (NA)
Total protein: End of IV therapy	-0.4 (9.76)	-3.3 (10.14)	3.0 (6.69)
Total protein: Test of Cure	5.8 (7.68)	2.1 (6.89)	6.4 (3.29)
Total protein: Early Follow-up	9.4 (5.13)	5.3 (3.27)	6.4 (4.98)
Total protein: Late Follow-up	8.2 (4.92)	5.3 (6.28)	4.8 (5.40)

2. Primary Outcome

Title	Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
CCE: On IV therapy (Day 5)	18.0 (NA)
CCE: Test of Cure	2.0 (NA)	13.0 (NA)	56.0 (NA)
CCE: Early Follow-up	1.0 (NA)	21.0 (NA)	60.0 (NA)
CCE: Late Follow-up	25.0 (NA)	21.0 (NA)

3. Primary Outcome

Title	Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Creatinine: On IV therapy (Day 5)	-4.20 (10.347)	-5.78 (13.336)	-11.97 (10.279)
Creatinine: On IV therapy (Day 11)	-1.50 (NA)
Creatinine: End of IV therapy	-0.24 (13.616)	-11.26 (12.634)	-8.70 (9.426)
Creatinine: Test of Cure	-2.17 (7.238)	-9.66 (11.743)	-8.54 (9.816)
Creatinine: Early Follow-up	-3.90 (6.134)	2.88 (14.662)	-4.56 (11.138)
Creatinine: Late Follow-up	4.43 (6.960)	-5.22 (10.760)	-5.22 (11.228)
Total bilirubin: On IV therapy (Day 3)	-7.5 (10.73)	-4.9 (4.45)	-7.2 (6.42)
Total bilirubin: On IV therapy (Day 5)	-7.0 (10.18)	-3.5 (5.57)	-7.3 (8.50)
Total bilirubin: On IV therapy (Day 8)	-5.0 (NA)	-4.5 (0.71)	-1.0 (NA)
Total bilirubin: On IV therapy (Day 11)	-1.0 (NA)
Total bilirubin: End of IV therapy	-8.2 (11.37)	-5.6 (0.71)	-5.5 (6.16)
Total bilirubin: Test of Cure	-7.7 (9.14)	-4.7 (5.00)	-6.4 (7.64)
Total bilirubin: Early Follow-up	-6.2 (8.29)	-4.5 (3.39)	-6.0 (7.04)
Total bilirubin: Late Follow-up	-5.2 (8.73)	-4.8 (4.12)	-5.0 (4.80)

4. Primary Outcome

Title	Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Calcium: On IV therapy (Day 5)	0.082 (0.1664)	-0.112 (0.2170)	0.060 (0.1229)
Calcium: On IV therapy (Day 11)	0.030 (NA)
Calcium: End of IV therapy	-0.020 (0.2411)	0.071 (0.1964)	0.078 (0.0930)
Calcium: Test of Cure	0.235 (0.2627)	0.096 (0.2057)	0.128 (0.1114)
Calcium: Early Follow-up	0.276 (0.1383)	0.120 (0.0919)	0.142 (0.1232)
Calcium: Late Follow-up	0.243 (0.0922)	0.115 (0.1027)	0.110 (0.1538)
C02 content/Bicarbonate: On IV therapy (Day 5)	-1.7 (3.01)	0.0 (2.83)	-2.0 (0.00)
C02 content/Bicarbonate: On IV therapy (Day 11)	-3.0 (NA)
C02 content/Bicarbonate: End of IV therapy	-2.4 (2.07)	0.6 (2.30)	-0.3 (2.88)
C02 content/Bicarbonate: Test of Cure	-0.8 (1.72)	2.7 (1.80)	1.4 (4.28)
C02 content/Bicarbonate: Early Follow-up	0.0 (3.81)	0.3 (1.63)	-0.4 (4.72)
C02 content/Bicarbonate: Late Follow-up	0.7 (2.34)	1.8 (2.71)	1.2 (4.97)
Chloride: On IV therapy (Day 5)	1.2 (4.07)	1.8 (3.50)	3.7 (1.15)
Chloride: On IV therapy (Day 11)	4.0 (NA)
Chloride: End of IV therapy	1.0 (3.74)	3.0 (3.83)	-0.2 (2.32)
Chloride: Test of Cure	0.5 (3.94)	1.0 (3.83)	0.2 (2.28)
Chloride: Early Follow-up	0.6 (4.72)	0.5 (4.51)	0.0 (2.35)
Chloride: Late Follow-up	0.3 (4.18)	-0.5 (3.02)	2.2 (0.84)
Glucose: On IV therapy (Day 5)	0.42 (1.993)	2.25 (1.700)	-2.00 (2.685)
Glucose: On IV therapy (Day 11)	1.50 (NA)
Glucose: End of IV therapy	-1.06 (1.372)	1.09 (1.542)	-0.68 (2.741)
Glucose: Test of Cure	-0.35 (1.649)	-0.11 (1.173)	-0.24 (2.261)
Glucose: Early Follow-up	-0.80 (1.158)	0.07 (1.316)	-0.78 (1.949)
Glucose: Late Follow-up	-0.45 (1.106)	0.58 (1.703)	-0.56 (2.395)
Potassium: On IV therapy (Day 5)	0.52 (0.662)	-0.05 (0.645)	0.37 (0.666)
Potassium: On IV therapy (Day 11)	0.00 (NA)
Potassium: End of IV therapy	0.46 (0.623)	0.24 (0.509)	0.48 (0.407)
Potassium: Test of Cure	0.78 (0.739)	0.40 (0.526)	0.44 (0.351)
Potassium: Early Follow-up	0.40 (0.725)	0.50 (0.400)	0.42 (0.327)
Potassium: Late Follow-up	0.28 (0.471)	0.53 (0.547)	0.40 (0.495)
Sodium: On IV therapy (Day 5)	1.2 (2.23)	0.3 (2.75)	2.3 (2.52)
Sodium: On IV therapy (Day 11)	4.0 (NA)
Sodium: End of IV therapy	0.4 (2.79)	1.7 (3.15)	-0.8 (2.14)
Sodium: Test of Cure	1.8 (1.33)	1.3 (3.40)	1.0 (1.73)
Sodium: Early Follow-up	1.8 (3.27)	-0.5 (3.45)	1.0 (1.58)
Sodium: Late Follow-up	1.2 (3.54)	-1.2 (4.36)	2.0 (2.65)
Urea/BUN: On IV therapy (Day 5)	-0.98 (2.024)	-0.45 (1.515)	-0.97 (0.874)
Urea/BUN: On IV therapy (Day 11)	-2.50 (NA)
Urea/BUN: End of IV therapy	-0.30 (2.633)	-1.13 (1.367)	-0.57 (1.046)
Urea/BUN: Test of Cure	-0.38 (1.184)	-0.73 (1.456)	-0.38 (1.033)
Urea/BUN: Early Follow-up	-0.64 (1.305)	0.20 (2.262)	-0.34 (0.853)
Urea/BUN: Late Follow-up	-0.30 (0.716)	-0.33 (1.199)	-0.12 (1.932)

5. Primary Outcome

Title	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)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
ALT: On IV therapy (Day 3)	5.7 (8.14)	10.4 (21.53)	12.8 (11.19)
ALT: On IV therapy (Day 5)	33.2 (46.82)	4.8 (8.85)	13.3 (17.90)
ALT: On IV therapy (Day 8)	4.0 (NA)	1.5 (6.36)	-3.0 (NA)
ALT: On IV therapy (Day 11)	2.0 (NA)
ALT: End of IV therapy	35.4 (40.46)	18.6 (21.35)	21.3 (29.30)
ALT: Test of Cure	17.5 (18.53)	7.3 (10.34)	7.0 (10.12)
ALT: Early Follow-up	4.8 (5.97)	1.0 (5.33)	5.8 (7.40)
ALT: Late Follow-up	3.3 (5.99)	-0.3 (4.32)	4.2 (5.50)
ALP: On IV therapy (Day 3)	10.8 (26.33)	14.3 (30.12)	13.2 (28.28)
ALP: On IV therapy (Day 5)	11.2 (22.99)	4.0 (27.14)	17.7 (35.50)
ALP: On IV therapy (Day 8)	-10.0 (NA)	21.5 (12.02)	-10.0 (NA)
ALP: On IV therapy (Day 11)	-11.0 (NA)
ALP: End of IV therapy	7.4 (26.28)	16.3 (34.62)	10.2 (22.60)
ALP: Test of Cure	10.8 (23.47)	6.9 (15.04)	14.8 (17.01)
ALP: Early Follow-up	7.4 (21.01)	1.2 (23.73)	8.2 (12.01)
ALP: Late Follow-up	5.7 (20.64)	2.3 (13.81)	3.6 (13.13)
AST: On IV therapy (Day 3)	5.0 (12.07)	4.1 (12.58)	19.2 (16.04)
AST: On IV therapy (Day 5)	31.5 (57.16)	6.3 (13.38)	20.0 (34.66)
AST: On IV therapy (Day 8)	-2.0 (NA)	2.0 (0.00)	2.0 (NA)
AST: On IV therapy (Day 11)	2.0 (NA)
AST: End of IV therapy	22.0 (34.71)	13.1 (15.08)	15.7 (23.34)
AST: Test of Cure	1.5 (9.81)	-2.3 (4.54)	-1.4 (6.50)
AST: Early Follow-up	-1.2 (8.56)	-4.8 (10.34)	1.2 (6.76)
AST: Late Follow-up	3.3 (15.02)	-3.3 (10.07)	3.4 (2.88)
Creatine kinase : On IV therapy (Day 5)	-76.0 (118.58)	-37.8 (46.94)	-26.0 (18.33)
Creatine kinase : On IV therapy (Day 11)	4.0 (NA)
Creatine kinase : End of IV therapy	-36.0 (33.56)	-165.6 (407.70)	-23.7 (18.33)
Creatine kinase : Test of Cure	-65.3 (129.24)	-156.4 (420.00)	18.4 (18.80)
Creatine kinase : Early Follow-up	-41.4 (158.04)	-218.2 (495.53)	-6.0 (30.12)
Creatine kinase : Late Follow-up	-37.8 (134.80)	-168.8 (448.90)	0.2 (41.05)
GGT : On IV therapy (Day 5)	41.7 (49.61)	6.5 (8.27)	24.0 (35.68)
GGT : On IV therapy (Day 11)	22.0 (NA)
GGT : End of IV therapy	35.8 (49.96)	28.9 (39.88)	14.0 (20.27)
GGT : Test of Cure	16.5 (20.67)	23.3 (24.69)	3.6 (8.76)
GGT : Early Follow-up	-1.4 (36.90)	8.3 (13.54)	-0.8 (12.15)
GGT : Late Follow-up	-16.7 (54.70)	1.3 (9.58)	-3.8 (12.03)

6. Primary Outcome

Title	Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description	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.
Time Frame	Up to 28 days post-therapy

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
AE	5 83.3%	6 75%	5 83.3%
SAE	1 16.7%	2 25%	0 0%

7. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	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.
Time Frame	Up to Late Follow-up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Day 1: Pre-dose 1	0 0%	4 50%	2 33.3%
Day 1: Pre-dose 2	2 33.3%	4 50%	2 33.3%
Day 1: Pre-dose 3	1 16.7%	2 25%	3 50%
Day 1: Post-dose	1 16.7%	5 62.5%	3 50%
Day 4 (on IV treatment): Pre-dose	2 33.3%	4 50%	2 33.3%
Day 4 (on IV treatment): Post-dose	3 50%	3 37.5%	2 33.3%
Early Follow-up	0 0%	3 37.5%	2 33.3%
Withdrawal	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description	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.
Time Frame	Up to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
SBP: Baseline (Day 1)	129.7 (29.27)	131.9 (14.56)	120.0 (17.64)
SBP: On IV therapy (Day 2)	131.2 (15.20)	125.4 (15.89)	120.0 (19.75)
SBP: On IV therapy (Day 3)	123.8 (15.09)	126.6 (28.69)	123.8 (13.88)
SBP: On IV therapy (Day 4)	137.8 (17.61)	127.0 (30.79)	124.2 (17.98)
SBP: On IV therapy (Day 5)	135.2 (27.58)	126.6 (35.10)	116.8 (18.42)
SBP: On IV therapy (Day 6)	150.0 (NA)	125.5 (34.65)	115.0 (12.25)
SBP: On IV therapy (Day 7)	165.0 (NA)	125.0 (21.21)	116.7 (20.82)
SBP: On IV therapy (Day 8)	170.0 (NA)	125.0 (49.50)	110.0 (NA)
SBP: On IV therapy (Day 9)	161.0 (NA)	130.0 (NA)	105.0 (NA)
SBP: On IV therapy (Day 10)	140.0 (NA)	110.0 (NA)
SBP: On IV therapy (Day 11)	155.0 (NA)
SBP: On IV therapy (Day 12)	140.0 (NA)
SBP: On IV therapy (Day 13)	130.0 (NA)
SBP: On IV therapy (Day 14)	152.0 (NA)
SBP: End of IV therapy	130.0 (17.03)	116.1 (13.93)	117.5 (11.73)
SBP: Test of Cure	131.3 (5.85)	126.9 (27.17)	126.4 (20.12)
SBP: Early Follow-up	128.0 (17.03)	120.1 (15.24)	123.8 (13.10)
SBP: Late Follow-up	148.0 (23.64)	117.6 (21.77)	116.6 (13.35)
DBP: Baseline (Day 1)	68.0 (12.84)	77.3 (9.25)	66.5 (4.64)
DBP: On IV therapy (Day 2)	78.3 (12.82)	69.0 (15.61)	70.3 (10.78)
DBP: On IV therapy (Day 3)	77.2 (12.22)	72.1 (15.72)	71.2 (3.56)
DBP: On IV therapy (Day 4)	85.5 (15.73)	79.5 (19.41)	69.6 (5.77)
DBP: On IV therapy (Day 5)	83.8 (13.95)	79.7 (21.89)	67.0 (4.12)
DBP: On IV therapy (Day 6)	90.0 (NA)	81.0 (12.73)	72.5 (15.00)
DBP: On IV therapy (Day 7)	85.0 (NA)	70.0 (0.00)	67.7 (9.29)
DBP: On IV therapy (Day 8)	90.0 (NA)	69.0 (15.56)	70.0 (NA)
DBP: On IV therapy (Day 9)	95.0 (NA)	80.0 (NA)	65.0 (NA)
DBP: On IV therapy (Day 10)	69.0 (NA)	70.0 (NA)
DBP: On IV therapy (Day 11)	69.0 (NA)
DBP: On IV therapy (Day 12)	75.0 (NA)
DBP: On IV therapy (Day 13)	80.0 (NA)
DBP: On IV therapy (Day 14)	69.0 (NA)
DBP: End of IV therapy	74.0 (9.94)	69.4 (17.22)	71.5 (12.42)
DBP: Test of Cure	82.2 (5.88)	70.6 (12.47)	71.8 (15.14)
DBP: Early Follow-up	73.8 (9.62)	72.0 (11.72)	68.8 (12.05)
DBP: Late Follow-up	87.7 (16.18)	67.5 (16.13)	65.0 (5.29)

9. Primary Outcome

Title	Summary of Vital Signs- Mean Heart Rate
Description	Vital sign measurements included heart rate. Measurements that deviated substantially from previous readings were repeated immediately. Mean heart rate is presented.
Time Frame	Up to Late Follow-up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Baseline (Day 1)	85.8 (10.63)	99.3 (13.78)	87.7 (11.78)
On IV therapy (Day 2)	78.2 (12.80)	83.0 (18.97)	81.5 (4.23)
On IV therapy (Day 3)	77.8 (4.92)	80.6 (14.79)	81.4 (9.40)
On IV therapy (Day 4)	78.5 (11.45)	81.0 (10.43)	73.6 (12.10)
On IV therapy (Day 5)	72.3 (13.52)	80.3 (10.55)	68.2 (11.45)
On IV therapy (Day 6)	89.0 (NA)	92.0 (16.97)	74.8 (6.70)
On IV therapy (Day 7)	81.0 (NA)	88.5 (16.26)	78.3 (9.07)
On IV therapy (Day 8)	88.0 (NA)	87.5 (6.36)	82.0 (NA)
On IV therapy (Day 9)	84.0 (NA)	80.0 (NA)	85.0 (NA)
On IV therapy (Day 10)	91.0 (NA)	86.0 (NA)
On IV therapy (Day 11)	100.0 (NA)
On IV therapy (Day 12)	84.0 (NA)
On IV therapy (Day 13)	90.0 (NA)
On IV therapy (Day 14)	92.0 (NA)
End of IV therapy	72.8 (11.82)	82.8 (8.91)	71.0 (7.32)
Test of Cure	74.5 (11.86)	73.6 (11.94)	74.6 (15.34)
Early Follow-up	72.5 (11.57)	74.0 (14.99)	65.8 (8.90)
Late Follow-up	76.8 (13.06)	71.8 (11.11)	78.2 (11.19)

10. Primary Outcome

Title	Summary of Vital Signs- Mean Respiration Rate
Description	Vital sign measurements included respiratory rate. Measurements that deviated substantially from previous readings were repeated immediately. Mean respiration rate are presented.
Time Frame	Up to Late Follow-up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Baseline (Day 1)	17.3 (2.94)	19.6 (3.85)	17.3 (3.27)
On IV therapy (Day 2)	15.0 (1.67)	18.1 (3.68)	16.8 (3.03)
On IV therapy (Day 3)	14.2 (1.33)	16.6 (3.62)	16.8 (4.27)
On IV therapy (Day 4)	15.5 (0.84)	17.3 (3.99)	17.8 (4.35)
On IV therapy (Day 5)	14.5 (1.52)	16.6 (3.46)	18.8 (3.59)
On IV therapy (Day 6)	16.0 (NA)	17.0 (4.24)	16.0 (4.32)
On IV therapy (Day 7)	16.0 (NA)	16.5 (3.54)	17.3 (4.16)
On IV therapy (Day 8)	16.0 (NA)	15.0 (1.41)	20.0 (NA)
On IV therapy (Day 9)	14.0 (NA)	16.0 (NA)	22.0 (NA)
On IV therapy (Day 10)	17.0 (NA)	20.0 (NA)
On IV therapy (Day 11)	15.0 (NA)
On IV therapy (Day 12)	16.0 (NA)
On IV therapy (Day 13)	14.0 (NA)
On IV therapy (Day 14)	14.0 (NA)
End of IV therapy	16.0 (2.45)	15.8 (2.96)	16.4 (2.19)
Test of Cure	14.0 (1.79)	15.5 (3.42)	18.2 (4.15)
Early Follow-up	15.3 (1.97)	15.9 (3.52)	16.4 (3.21)
Late Follow-up	13.4 (1.95)	16.0 (2.78)	16.6 (3.71)

11. Primary Outcome

Title	Summary of Vital Signs- Mean Temperature
Description	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).
Time Frame	Up to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Baseline (Day 1)	38.08 (0.741)	38.41 (0.946)	38.30 (0.469)
On IV therapy (Day 2)	36.97 (1.063)	37.30 (0.693)	37.30 (0.860)
On IV therapy (Day 3)	36.75 (0.706)	36.79 (0.380)	37.74 (0.817)
On IV therapy (Day 4)	36.60 (0.469)	36.71 (0.669)	37.38 (0.986)
On IV therapy (Day 5)	36.27 (0.378)	36.59 (0.498)	36.96 (0.654)
On IV therapy (Day 6)	37.00 (NA)	36.90 (1.273)	36.40 (0.283)
On IV therapy (Day 7)	36.20 (NA)	36.95 (0.778)	36.93 (0.416)
On IV therapy (Day 8)	36.80 (NA)	36.80 (0.707)	36.50 (NA)
On IV therapy (Day 9)	36.50 (NA)	36.80 (NA)	36.50 (NA)
On IV therapy (Day 10)	37.00 (NA)	36.50 (NA)
On IV therapy (Day 11)	37.00 (NA)
On IV therapy (Day 12)	36.80 (NA)
On IV therapy (Day 13)	36.20 (NA)
On IV therapy (Day 14)	36.80 (NA)
End of IV therapy	36.18 (0.512)	36.75 (0.676)	36.38 (0.299)
Test of Cure	36.25 (0.418)	35.98 (0.709)	36.14 (0.744)
Early Follow-up	36.23 (0.427)	35.99 (0.387)	36.28 (0.606)
Late Follow-up	36.40 (0.110)	36.08 (0.512)	36.00 (0.394)

12. Primary Outcome

Title	Therapeutic Response at the Test of Cure Visit
Description	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.
Time Frame	Test of Cure Visit (5 to 9 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	5
Therapeutic Success	1 16.7%	5 62.5%	1 16.7%
Therapeutic Failure	5 83.3%	3 37.5%	4 66.7%

13. Primary Outcome

Title	Change From Baseline in Hematology Parameters- Hematocrit
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
End of IV therapy	-0.0140 (0.06893)	-0.0155 (0.06930)	-0.0120 (0.02993)
Late Follow-up	0.0373 (0.03079)	-0.0007 (0.03322)	-0.0038 (0.01669)

14. Primary Outcome

Title	Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
End of IV therapy	-0.60 (0.748)	-0.60 (0.668)	-0.07 (0.628)
Late Follow-up	-0.85 (0.657)	-0.89 (0.573)	-0.14 (0.472)

15. Primary Outcome

Title	Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
End of IV therapy	-3.0 (2.45)	-1.3 (1.98)	-1.0 (0.89)
Late Follow-up	-2.2 (0.98)	-1.3 (2.75)	-0.8 (1.79)

16. Primary Outcome

Title	Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
RBC: End of IV therapy	-0.10 (0.689)	-0.10 (0.707)	-0.08 (0.360)
RBC: Late Follow-up	0.52 (0.366)	0.07 (0.236)	0.02 (0.228)
Reticulocytes: End of IV therapy	-0.0331 (0.04544)	-0.0312 (0.02489)	-0.0072 (0.02295)
Reticulocytes: Late Follow-up	-0.0466 (0.09881)	-0.0092 (0.03267)	0.0080 (0.02577)

17. Primary Outcome

Title	Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Hemoglobin: End of IV therapy	-3.0 (22.77)	-5.5 (21.36)	-2.5 (8.17)
Hemoglobin: Late Follow-up	11.0 (7.24)	-2.1 (9.67)	-0.6 (4.16)
MCHC: End of IV therapy	4.0 (3.81)	-1.8 (6.50)	4.2 (6.74)
MCHC: Late Follow-up	-3.0 (8.44)	-5.0 (5.94)	1.8 (8.29)

18. Primary Outcome

Title	Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC)
Description	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.
Time Frame	Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	6
Basophils: End of IV therapy	0.028 (0.0084)	0.018 (0.0116)	0.014 (0.0182)
Basophils: Late Follow-up	0.022 (0.0147)	0.020 (0.0163)	0.016 (0.0114)
Eosinophils: End of IV therapy	0.274 (0.1389)	0.096 (0.0980)	0.090 (0.0682)
Eosinophils: Late Follow-up	0.093 (0.1488)	0.067 (0.0966)	0.086 (0.0385)
Lymphocytes: End of IV therapy	0.580 (1.2076)	0.514 (0.3816)	0.596 (0.5140)
Lymphocytes: Late Follow-up	0.687 (1.5191)	0.774 (0.4808)	0.436 (0.7578)
Monocytes: End of IV therapy	-0.188 (0.3739)	-0.256 (0.2015)	-0.442 (0.3841)
Monocytes: Late Follow-up	-0.380 (0.4553)	-0.230 (0.3902)	-0.186 (0.2103)
Platelet count: End of IV therapy	141.0 (171.58)	83.2 (139.06)	105.4 (92.20)
Platelet count: Late Follow-up	48.8 (129.10)	45.4 (34.93)	39.8 (35.81)
Total neutrophils: End of IV therapy	-8.178 (3.6642)	-6.695 (4.6214)	-4.656 (6.6652)
Total neutrophils: Late Follow-up	-6.765 (4.0488)	-7.737 (6.3494)	-7.902 (8.1795)
WBC count: End of IV therapy	-7.48 (4.242)	-6.30 (4.607)	-4.36 (6.696)
WBC count: Late Follow-up	-6.33 (4.918)	-7.11 (6.207)	-7.54 (8.486)

19. Secondary Outcome

Title	Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

MITT Population.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	5
Microbiological Success	3 50%	5 62.5%	5 83.3%
Microbiological Failure	3 50%	3 37.5%	0 0%
Microbiological Success	1 16.7%	5 62.5%	1 16.7%
Microbiological Failure	5 83.3%	3 37.5%	4 66.7%
Microbiological Success	2 33.3%	6 75%	1 16.7%
Microbiological Failure	4 66.7%	2 25%	4 66.7%

20. Secondary Outcome

Title	Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

MITT Population.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	5
Clinical Success	4 66.7%	6 75%	5 83.3%
Clinical Failure	2 33.3%	2 25%	0 0%
Clinical Success	4 66.7%	6 75%	4 66.7%
Clinical Failure	2 33.3%	2 25%	1 16.7%
Clinical Success	3 50%	6 75%	2 33.3%
Clinical Failure	3 50%	2 25%	3 50%

21. Secondary Outcome

Title	Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit
Description	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.
Time Frame	End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)

Outcome Measure Data

Analysis Population Description

MITT Population.

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	6	8	5
Therapeutic Success	3 50%	5 62.5%	5 83.3%
Therapeutic Failure	3 50%	3 37.5%	0 0%
Therapeutic Success	2 33.3%	6 75%	1 16.7%
Therapeutic Failure	4 66.7%	2 25%	4 66.7%

22. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of GSK2251052
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

23. Secondary Outcome

Title	Area Under the Concentration Time Curve (AUC) of GSK2251052
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

24. Secondary Outcome

Title	Time to Cmax (Tmax) of GSK2251052
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

25. Secondary Outcome

Title	Cmax of GSK2251052 Using Non-intensive PK Sampling
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

26. Secondary Outcome

Title	AUC of GSK2251052 Using Non-intensive PK Sampling
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

27. Secondary Outcome

Title	Tmax of GSK2251052 Using Non-intensive PK Sampling
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

28. Secondary Outcome

Title	Cmax of GSK2251052 Using Intensive PK Sampling
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

29. Secondary Outcome

Title	AUC of GSK2251052 Using Intensive PK Sampling
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

30. Secondary Outcome

Title	Tmax of GSK2251052 Using Intensive PK Sampling
Description	The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GSK2251052 750 mg	GSK2251052 1500 mg	Imipenem-Cilastatin
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

Adverse Events

Time Frame	Up to 28 days post-therapy
Adverse Event Reporting Description	SAE and non-SAE are reported for the Safety population which consisted of all participants who received at least one dose of study medication.
Arm/Group Title	GSK2251052 750 mg		GSK2251052 1500 mg		Imipenem-Cilastatin
Arm/Group Description	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.		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.		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.
All Cause Mortality
	GSK2251052 750 mg		GSK2251052 1500 mg		Imipenem-Cilastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/6 (0%)
Serious Adverse Events
	GSK2251052 750 mg		GSK2251052 1500 mg		Imipenem-Cilastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		2/8 (25%)		0/6 (0%)
Cardiac disorders
Cardiac arrest	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Infections and infestations
Escherichia bacteraemia	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Investigations
Aspiration bronchial	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Haemoglobin decreased	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/6 (16.7%)		0/8 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	GSK2251052 750 mg		GSK2251052 1500 mg		Imipenem-Cilastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		5/8 (62.5%)		5/6 (83.3%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Thrombocytopenia	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Eye disorders
Eyelid oedema	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Gastrointestinal disorders
Nausea	0/6 (0%)		2/8 (25%)		1/6 (16.7%)
Abdominal pain upper	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Dyspepsia	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Rectal haemorrhage	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Small intestinal obstruction	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Vomiting	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
General disorders
Chest pain	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Papillitis	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Infections and infestations
Pharyngitis	1/6 (16.7%)		0/8 (0%)		1/6 (16.7%)
Oral herpes	1/6 (16.7%)		0/8 (0%)		0/6 (0%)
Vulvovaginal candidiasis	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Investigations
Alanine aminotransferase increased	1/6 (16.7%)		2/8 (25%)		0/6 (0%)
Aspartate aminotransferase increased	1/6 (16.7%)		1/8 (12.5%)		0/6 (0%)
Haemoglobin decreased	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Nervous system disorders
Dizziness	1/6 (16.7%)		0/8 (0%)		2/6 (33.3%)
Headache	0/6 (0%)		0/8 (0%)		2/6 (33.3%)
Paraesthesia	1/6 (16.7%)		0/8 (0%)		0/6 (0%)
Psychiatric disorders
Depression	1/6 (16.7%)		0/8 (0%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		0/8 (0%)		1/6 (16.7%)
Nasal congestion	1/6 (16.7%)		0/8 (0%)		0/6 (0%)
Vascular disorders
Phlebitis	0/6 (0%)		1/8 (12.5%)		1/6 (16.7%)
Deep vein thrombosis	1/6 (16.7%)		0/8 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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