Infections, Urinary TractPhase 2NCT01381549

GSK2251052 in Complicated Urinary Tract Infection

A Phase 2 study testing GSK2251052 and imipenem-cilastatin in people with Infections, Urinary Tract, run by GlaxoSmithKline at 24 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Infections, Urinary Tract
What is being tested?: GSK2251052 and imipenem-cilastatin
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 24 sitesin 6 countries
Study dates: 28 Jun 2011to 6 Mar 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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,

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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

Who cannot join

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

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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

Trial locations and contacts

24 sites in 6 countries.

Country

City, postcode or hospital

24 sites in 6 countries

Spain7 sites

GSK Investigational Site
Alicante, 03010
GSK Investigational Site
Elche (Alicante), 03203
GSK Investigational Site
Getafe/Madrid, 28905
GSK Investigational Site
Granada, 18003
GSK Investigational Site
Madrid, 28040
GSK Investigational Site
Murcia
GSK Investigational Site
Pama de Mallorca, 07010

Other trials in Spain

Russia5 sites

GSK Investigational Site
Irkutsk, 664079
GSK Investigational Site
Moscow, 125367
GSK Investigational Site
Rostov-on-Don, 344022
GSK Investigational Site
Smolensk, 214018
GSK Investigational Site
St'Petersburg, 194354

Other trials in Russia

United States4 sites

GSK Investigational Site
Corsicana, Texas, 75110
GSK Investigational Site
Council Bluffs, Iowa, 51503
GSK Investigational Site
Los Angeles, California, 90033
GSK Investigational Site
Topeka, Kansas, 66604

Other trials in United States

Greece4 sites

GSK Investigational Site
Athens, 11527
GSK Investigational Site
Chaïdári, 12462
GSK Investigational Site
Goudi, Athens, 11527
GSK Investigational Site
Thessaloniki, 56429

Other trials in Greece

Canada2 sites

GSK Investigational Site
Chicoutimi, Quebec, G7H 5H6
GSK Investigational Site
Sherbrooke, Quebec, J1H 5N4

Other trials in Canada

France2 sites

GSK Investigational Site
Suresnes, 92151
GSK Investigational Site
Toulouse, 31059

Other trials in France

About this study

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

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.

Conditions: Infections, Urinary Tract
Being tested: GSK2251052, imipenem-cilastatin, Placebo
Keywords: Gram-negative, uropathogens, complicated lower urinary tract infection, pyelonephritis
Medical subject headings: Urinary Tract Infections, Pyelonephritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2251052Drug
Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion
imipenem-cilastatinDrug
Also called Primaxin® (Manufacturer: Merck)
Prepare as per prescribing information instructions in 100 mL bag of 0.9% NaCl and administered via IV infusion
PlaceboOther
saline placebo

Study groups in NCT01381549
Study group	Role	What they receive
GSK2251052 750mg	Experimental	q12h administered via IV infusion, plus saline placebo Receives: Drug: GSK2251052; Other: Placebo
GSK2251052 1500mg	Experimental	q12h administered via IV infusion, plus saline placebo Receives: Drug: GSK2251052; Other: Placebo
imipenem-cilastatin	Active comparator	500 mg imipenem monohydrate and 500 mg cilastatin sodium; q6h administered via IV infusion, plus saline placebo Receives: Drug: imipenem-cilastatin; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
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)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
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.
Measured: Up to 28 days post-therapy
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
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.
Measured: Up to Late Follow-up Visit (21 to 28 days post-IV therapy)
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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.
Measured: Up to Late Follow up Visit (21 to 28 days post-IV therapy)
Summary of Vital Signs- Mean Heart Rate
Vital sign measurements included heart rate. Measurements that deviated substantially from previous readings were repeated immediately. Mean heart rate is presented.
Measured: Up to Late Follow-up Visit (21 to 28 days post-IV therapy)
Summary of Vital Signs- Mean Respiration Rate
Vital sign measurements included respiratory rate. Measurements that deviated substantially from previous readings were repeated immediately. Mean respiration rate are presented.
Measured: Up to Late Follow-up Visit (21 to 28 days post-IV therapy)
Summary of Vital Signs- Mean Temperature
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).
Measured: Up to Late Follow up Visit (21 to 28 days post-IV therapy)
Therapeutic Response at the Test of Cure Visit
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.
Measured: Test of Cure Visit (5 to 9 days post-IV therapy)
Change From Baseline in Hematology Parameters- Hematocrit
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC)
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.
Measured: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)

Secondary outcomes (12)

Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit
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.
Measured: 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 at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit
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.
Measured: 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)
Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit
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.
Measured: End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)
Maximum Plasma Concentration (Cmax) of GSK2251052
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
Area Under the Concentration Time Curve (AUC) of GSK2251052
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
Time to Cmax (Tmax) of GSK2251052
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
Cmax of GSK2251052 Using Non-intensive PK Sampling
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
AUC of GSK2251052 Using Non-intensive PK Sampling
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
Tmax of GSK2251052 Using Non-intensive PK Sampling
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
Cmax of GSK2251052 Using Intensive PK Sampling
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
AUC of GSK2251052 Using Intensive PK Sampling
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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
Tmax of GSK2251052 Using Intensive PK Sampling
The planned pharmacokinetic (PK) and PK/pharmacodynamic analyses were not performed, because the PK data was not collected.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jun 20116 Mar 2012

First posted27 Jun 2011 (estimated)
Study start28 Jun 2011
Primary completion6 Mar 2012
Study completion6 Mar 2012

Why it stopped: Microbiological findings of resistance on therapy in patients with complicated urinary tract infection

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infections, Urinary TractStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01381549
Sponsor's protocol ID: 114688
Status last verified: Aug 2017
First submitted: 9 Jun 2011
Last updated: 8 Sep 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

O'Dwyer K, Spivak AT, Ingraham K, Min S, Holmes DJ, Jakielaszek C, Rittenhouse S, Kwan AL, Livi GP, Sathe G, Thomas E, Van Horn S, Miller LA, Twynholm M, Tomayko J, Dalessandro M, Caltabiano M, Scangarella-Oman NE, Brown JR. Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections. Antimicrob Agents Chemother. 2015 Jan;59(1):289-98. doi: 10.1128/AAC.03774-14. Epub 2014 Oct 27.
PubMed 25348524

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01381549
Acronym / sponsor ID: 114688
Conditions: Infections, Urinary Tract
Keywords: Gram-negative, uropathogens, complicated lower urinary tract infection, pyelonephritis
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Microbiological findings of resistance on therapy in patients with complicated urinary tract infection
Enrolment: 20 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 28 Jun 2011 (actual)
Primary completion: 6 Mar 2012 (actual)
Study completion: 6 Mar 2012 (actual)
First posted: 27 Jun 2011 (estimated)
Results: Posted 8 Sep 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
GSK2251052 750mg	Experimental	Drug: GSK2251052, Other: Placeboq12h administered via IV infusion, plus saline placebo
GSK2251052 1500mg	Experimental	Drug: GSK2251052, Other: Placeboq12h administered via IV infusion, plus saline placebo
imipenem-cilastatin	Active comparator	Drug: imipenem-cilastatin, Other: Placebo500 mg imipenem monohydrate and 500 mg cilastatin sodium; q6h administered via IV infusion, plus saline placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (29 listed)

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

Key exclusion criteria (33 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK2251052Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion	Drug	GSK2251052 1500mg, GSK2251052 750mg
imipenem-cilastatinAlso: Primaxin® (Manufacturer: Merck)Prepare as per prescribing information instructions in 100 mL bag of 0.9% NaCl and administered via IV infusion	Drug	imipenem-cilastatin
Placebosaline placebo	Other	GSK2251052 1500mg, GSK2251052 750mg, imipenem-cilastatin

Primary outcome

Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein
Time frame: 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.
Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE)
Time frame: 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.
Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin
Time frame: 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.
Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)
Time frame: 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.
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)
Time frame: 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.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: 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.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: 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.
Summary of Vital Signs: Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: 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.
Summary of Vital Signs- Mean Heart Rate
Time frame: 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.
Summary of Vital Signs- Mean Respiration Rate
Time frame: 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.
Summary of Vital Signs- Mean Temperature
Time frame: 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).
Therapeutic Response at the Test of Cure Visit
Time frame: 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.
Change From Baseline in Hematology Parameters- Hematocrit
Time frame: 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.
Change From Baseline in Hematology Parameters- Mean Corpuscle Hemoglobin (MCH)
Time frame: 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.
Change From Baseline in Hematology Parameters- Mean Corpuscle Volume (MCV)
Time frame: 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.
Change From Baseline in Hematology Parameters- Red Blood Cell (RBC) Count and Reticulocytes
Time frame: 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.
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
Time frame: 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.
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils and White Blood Cell Count (WBC)
Time frame: 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.

12 secondary outcomes

Microbiological Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit
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)
Clinical Response at the End of IV Therapy Visit, Test of Cure Visit and Late Follow-Up Visit
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)
Therapeutic Response (Combined Clinical and Microbiological Response) at the End of IV Visit and Late Follow-Up Visit
Time frame: End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)
Maximum Plasma Concentration (Cmax) of GSK2251052
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
Area Under the Concentration Time Curve (AUC) of GSK2251052
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
Time to Cmax (Tmax) of GSK2251052
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
Cmax of GSK2251052 Using Non-intensive PK Sampling
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
AUC of GSK2251052 Using Non-intensive PK Sampling
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
Tmax of GSK2251052 Using Non-intensive PK Sampling
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
Cmax of GSK2251052 Using Intensive PK Sampling
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
AUC of GSK2251052 Using Intensive PK Sampling
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
Tmax of GSK2251052 Using Intensive PK Sampling
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

Results and safety

Results posted to the registry on 8 Sep 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GSK2251052 750 mg	6	6
GSK2251052 1500 mg	8	8
Imipenem-Cilastatin	6	5

Primary outcome: Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein

Time frame: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy). Mean (Standard Deviation). Unit: Gram per Liter

Measure	GSK2251052 750 mg n = 6	GSK2251052 1500 mg n = 8	Imipenem-Cilastatin n = 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)	–	–

Population analysed: 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.

Primary outcome: Change From Baseline in Clinical Laboratory Parameters- Creatinine Clearance, Estimated (CCE)

Time frame: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy). Mean (Standard Deviation). Unit: Milliliter per minute

Measure	GSK2251052 750 mg n = 6	GSK2251052 1500 mg n = 8	Imipenem-Cilastatin n = 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)	–

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

Primary outcome: Change From Baseline in Clinical Laboratory Parameters- Creatinine, Direct Bilirubin and Total Bilirubin

Time frame: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy). Mean (Standard Deviation). Unit: Micromole per liter

Measure	GSK2251052 750 mg n = 6	GSK2251052 1500 mg n = 8	Imipenem-Cilastatin n = 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)

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

Primary outcome: Change From Baseline in Clinical Laboratory Parameters- Calcium, Carbon-dioxide (C02) Content/Bicarbonate, Chloride, Glucose, Potassium, Sodium and Urea/Blood Urea Nitrogen (BUN)

Time frame: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy). Mean (Standard Deviation). Unit: Millimole per Liter

Measure	GSK2251052 750 mg n = 6	GSK2251052 1500 mg n = 8	Imipenem-Cilastatin n = 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)	–	–

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

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 28 days post-therapy. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GSK2251052 750 mg	1 of 6 (16.7%)	5 of 6 (83.3%)	0 of 6
GSK2251052 1500 mg	2 of 8 (25%)	5 of 8 (62.5%)	0 of 8
Imipenem-Cilastatin	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25348524O'Dwyer K, Spivak AT, Ingraham K, Min S, Holmes DJ, Jakielaszek C, Rittenhouse S, Kwan AL, Livi GP, Sathe G, Thomas E, Van Horn S, Miller LA, Twynholm M, Tomayko J, Dalessandro M, Caltabiano M, Scangarella-Oman NE, Brown JR. Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections. Antimicrob Agents Chemother. 2015 Jan;59(1):289-98. doi: 10.1128/AAC.03774-14. Epub 2014 Oct 27.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

24 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK2251052 and imipenem-cilastatin in people with Infections, Urinary Tract, run by GlaxoSmithKline at 24 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Spain, Russia, United States, Greece, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Clinical Laboratory Parameters- Albumin and Total Protein (time frame: Baseline (Day 1) to Late Follow up Visit (21 to 28 days post-IV therapy)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01381549, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2017.