Infections, IntestinalPhase 2NCT01381562

GSK2251052 in the Treatment of Complicated Intra-abdominal Infections

A Phase 2 study testing Drug: GSK2251052 and Meropenem in people with Infections, Intestinal, run by GlaxoSmithKline at 31 sites in 7 countries.

Terminated

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

Official record

Search all trials

Trial summary

This study is being conducted to evaluate the safety, efficacy and pharmacokinetics/pharmacodynamics of GSK2251052 in subjects with complicated intra abdominal infections. GSK2251052 will be compared to meropenem, an IV therapy that is approved for use in the treatment of subjects with cIAI. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Infections, Intestinal
What is being tested?: Drug: GSK2251052 and Meropenem
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 15 participants
Where: 31 sitesin 7 countries
Study dates: 3 Oct 2011to 5 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. It is not contraindicated to enrol females of childbearing potential; however, 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,

Show all 38Show fewer

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 has evidence of a systemic inflammatory response believed to be related to an intra-abdominal infectious process with no evidence of another infectious source (e.g., catheter related, lung, urinary tract)
Subject has an abnormal white blood cell count (>12,000/µL or <4,000/µL or >10% bands) PLUS one or more of the following
Fever, defined as >38°C oral, >38.5°C tympanic or >39°C rectal, within the last 24 hours
Heart rate of more than 90 beats per minute
Respiratory rate of more than 20 breaths per minute or a PaCO2 level of less than 32 mm Hg
Altered mental status thought due to an infectious process
Subject is post-op and required surgery within the last 24 hours prior to first dose of study medication OR subject requires surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous drainage of an abscess) within 24 hours of first dose of study medication with no more than one pre-surgical dose of an antibiotic given for pre-operative prophylaxis.
Subject has a known Gram-negative pathogen(s) isolated prior to study entry or a suspected Gram-negative post-operative infection or has failed a prior Gram negative treatment regimen
A subject enrolled as a failure of a previous antibacterial treatment regimen must:
Show lack of improvement or worsening in signs and symptoms of infection, including continued or worsening peritoneal findings Require additional surgical intervention which must be performed within 24 hours of first dose of study medication with no more than one pre-surgical dose of an antibiotic given for pre-operative prophylaxis AND/OR Be post-op and have required surgery within 24 hours prior to first dose of study medication with no more than one pre-surgical dose of an antibiotic given for pre-operative prophylaxis.
Have a culture positive for a Gram-negative pathogen (from an intra-abdominal site) N.B. Such subjects may be enrolled before the results of the culture are known but if the culture is negative, the subject must be removed from study drug therapy.
Subject requires antibacterial therapy for an anticipated duration of 7 days or more, in addition to surgical intervention, for one of the following eligible diagnoses:
Cholecystitis (including gangrenous cholecystitis) with rupture, perforation or progression of the infection beyond the gallbladder wall
Diverticular disease with perforation or abscess
Appendiceal perforation with duration of symptoms >=48 hours AND imaging that is strongly suggestive of free fluid or abscess
Acute gastric and duodenal perforations, only if operated more than 24 hours after perforation occurred
Traumatic perforation of the intestine only if operated more than 12 hours after perforation occurred
Peritonitis due to perforated viscus, post-operative, or other focus of infection (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites)
Inflammatory bowel disease or ischemic bowel disease with bowel perforation
If pre-operative, subject must have peritoneal findings highly suspicious for cIAI, defined as one or more of the following:
Abdominal pain and/or tenderness
Localized or diffuse abdominal wall rigidity
An imaging procedure, ie. ultrasound or CT scan showing evidence of IAI
Mass
Ileus
QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block

Who cannot join

Subject has a known or suspected diagnosis of the following:
Abdominal wall abscess
Small bowel obstruction or ischemic bowel disease without perforation
Traumatic bowel perforation with surgery within 12 hours
Perforation of gastroduodenal ulcer with surgery within 24 hours
Any other intra-abdominal processes in which the primary etiology is not likely to be infectious.

Show all 31Show fewer

Simple cholecystitis
Gangrenous or suppurative cholecystitis without rupture or extension beyond the gallbladder wall
Simple appendicitis
Acute suppurative cholangitis
Infected, necrotizing pancreatitis, or pancreatic abscess
Subject must not be managed by staged abdominal repair or open abdominal technique
Subject is known at study entry, prior to randomization to study medication, to have a cIAI caused by a Gram-positive pathogen or a pathogen resistant to the study antimicrobial agent.
Subject has an APACHE II score >20.
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 requires treatment with concomitant systemic antibacterial agents other than vancomycin.
Subject has moderate to severe impairment of renal function including a calculated creatinine clearance (CrCl) of less than 50 mL/min; requirement for peritoneal dialysis, hemodialysis, or hemofiltration; or oliguria (less than 20 mL urine output per hour over 24 hours).
Subject has a prior history of seizures or CNS abnormality and/or is using concomitant medications with seizure potential
Subject requires probenecid or valproic acid medications
Subject has evidence of known or pre-existing severe hepatic disease(Child-Pugh score of B or C)
Subject has a known baseline hemoglobin less than 10 g/dL ,hematocrit less than 30% and/or a known reticulocyte count of >5% (ie, reticulocytes >5% of total RBC mass)
Subject has known neutropenia or is anticipated to develop neutropenia during the course of the study (ie, new chemotherapy patient), 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) transplant recipients, and hematological malignancy, and immunosuppressive therapy , including high-dose corticosteroids (e.g., greater than 40mg 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 had more than 24 hours of systemic antibacterial therapy for cIAI within the 48 hour period prior to first dose of IV study drug therapy, unless there is a documented lack of clinical response to such therapy
Subject has a history of moderate or severe hypersensitivity to Meropenem or to beta-lactam antibiotics
Subject has previously received treatment with GSK2251052
Subject is pregnant or nursing.
Subject, in the opinion of the investigator, may be significantly compromised by a potential drop in haemoglobin greater than 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

31 sites in 7 countries.

Country

City, postcode or hospital

31 sites in 7 countries

United States12 sites

GSK Investigational Site
Buffalo, New York, 14215
GSK Investigational Site
Columbus, Ohio, 43215
GSK Investigational Site
Council Bluffs, Iowa, 51503
GSK Investigational Site
Jacksonville, Florida, 32209
GSK Investigational Site
Las Vegas, Nevada, 89109
GSK Investigational Site
Lima, Ohio, 45801
GSK Investigational Site
Long Beach, California, 90822
GSK Investigational Site
Mobile, Alabama, 36617
GSK Investigational Site
New Orleans, Louisiana, 70112
GSK Investigational Site
Richmond, Virginia, 23298
GSK Investigational Site
Topeka, Kansas, 66604
GSK Investigational Site
Torrance, California, 90509

Other trials in United States

Russia5 sites

GSK Investigational Site
Irkutsk, 664079
GSK Investigational Site
Perm, 614036
GSK Investigational Site
Perm, 614068
GSK Investigational Site
Saint Petersburgh, 192242
GSK Investigational Site
Smolensk, 214019

Other trials in Russia

Canada4 sites

GSK Investigational Site
Chicoutimi, Quebec, G7H 5H6
GSK Investigational Site
Saskatoon, Saskatchewan, S7N 0W8
GSK Investigational Site
Sherbrooke, Quebec, J1H 5N4
GSK Investigational Site
Trois-Rivières, Quebec, G8Z 3R9

Other trials in Canada

Spain4 sites

GSK Investigational Site
Alicante, 03010
GSK Investigational Site
Elche (Alicante), 03203
GSK Investigational Site
Madrid, 28006
GSK Investigational Site
Pama de Mallorca, 07010

Other trials in Spain

France3 sites

GSK Investigational Site
Limoges, 87042
GSK Investigational Site
Nîmes, 30029
GSK Investigational Site
Strasbourg, 67200

Other trials in France

Czechia2 sites

GSK Investigational Site
Prague, 100 34
GSK Investigational Site
Prague, 10034

Other trials in Czechia

Italy1 site

GSK Investigational Site
Verona, Veneto, 37134

Other trials in Italy

About this study

Official title: A Study to Assess the Safety, Tolerability and Preliminary Efficacy of GSK2251052 in the Treatment of Complicated Intra-abdominal Infection in Adults

Conditions: Infections, Intestinal
Being tested: Drug: GSK2251052, Meropenem, Placebo
Keywords: intra-abdominal infection, belly, Gram-negative pathogen, abscess, peritonitis
Medical subject headings: Infections, Intraabdominal Infections, Abscess, Peritonitis

What participants receive

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

Drug: GSK2251052Drug
Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion
MeropenemDrug
Also called Merrem ®, Meronem
Reconstituted, added to 100mL 0.9% NaCl solution and administered via IV infusion
PlaceboOther
saline placebo

Study groups in NCT01381562
Study group	Role	What they receive
GSK2251052 750mg	Experimental	q12h administered via IV infusion, plus saline placebo Receives: Drug: Drug: GSK2251052; Other: Placebo
GSK2251052 1500mg	Experimental	q12h administered via IV infusion, plus saline placebo Receives: Drug: Drug: GSK2251052; Other: Placebo
Meropenem 1G	Active comparator	q8h administered via IV infusion, plus saline placebo Receives: Drug: Meropenem; Other: Placebo

What is being measured

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

Number of Participants With Any Adverse Event
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE included AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition
Measured: Up to Day 42
Number of Participants With Clinically Significant Trends in Vital Signs Over the Period of Study Duration
Vital parameters including systolic and diastolic blood pressure, heart rate, respiration rate, and temperature were recorded. The number of participants with potentially clinically concern value of any vital parameter at any visit were reported.
Measured: Up to Day 42
Number of Participants With Normal and Abnormal ECG Findings
12-lead ECGs was obtained during the study using an ECG machine and performed with the participant in a semi-supine position rested in this position for at least 10 minutes beforehand. Measurements deviated substantially from previous readings were repeated immediately. Number of participants with normal and abnormal ECG findings were reported.
Measured: Up to Day 42
Laboratory Parameters of Interest- Mean Hemoglobin Over the Period of Study Duration
Absolute mean hemoglobin values recorded over the period of duration were reported.
Measured: Up to Day 42
Laboratory Parameters of Interest- Mean Reticulocytes Over the Period of Study Duration
Absolute mean reticulocytes values recorded over the period of duration were reported.
Measured: Up to 42 days
Mean Change From Baseline in Hemoglobin for Partcipants With Significant Hemoglobin Drop
Participants in whom the hemoglobin level dropped by more than 30% from Baseline that was not attributable to acute blood loss were recorded and immediately withdrawn from study treatment. Baseline assessments were recorded on Visit 1 (Day 1) and used as Baseline values. The change from Baseline was calculated by subtracting the Baseline values from Day 42 values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing. The mean change from Baseline in hemoglobin for participants with significant hemoglobin drop were reported.
Measured: Baseline (Day 1) and up to Day 42
Number of Participants With Clinical Response at Test of Cure Visit (5-9 Days Post-therapy) in Microbiological Intent to Treat (MITT) Population
Test of cure-clinical success was resolution of signs and symptoms of complicated intra-abdominal infection (cIAI) for participants who were clinical successes at the end of IV therapy visit with no new symptoms recorded that were not present at Baseline and no use of additional antibiotic therapy for cIAI. Test of cure-clinical failure was persistence of signs and symptoms of cIAI recorded at Baseline, or reappearance of signs and symptoms that had previously resolved, or new signs and symptoms recorded that were not present at a previous visit, or receipt of additional or alternate antibiotic therapy for cIAI or participant had died. Test of cure- unable to determine was refusal to consent to a clinical examination, lost to follow-up. Participants who were 'unable to determine' at End of IV therapy were considered 'unable to determine' Test of cure Visit as well. Due to early termination of the study, a Bayesian approach for informal hypothesis testing was not performed.
Measured: Day 5 to 9 post IV therapy

Secondary outcomes (16)

Number of Participants With Clinical Response at Test of Cure Visit (5-9 Days Post-therapy) in Microbiological Evaluable Population.
Test of cure-clinical success was resolution of signs and symptoms of complicated intra-abdominal infection (cIAI) for participants who were clinical successes at the end of IV therapy visit with no new symptoms recorded that were not present at Baseline and no use of additional antibiotic therapy for cIAI. Test of cure-clinical failure was persistence of signs and symptoms of cIAI recorded at Baseline, or reappearance of signs and symptoms that had previously resolved, or new signs and symptoms recorded that were not present at a previous visit, or receipt of additional or alternate antibiotic therapy for cIAI or participant had died. Test of cure- unable to determine was refusal to consent to a clinical examination, lost to follow-up. Participants who were 'unable to determine' at End of IV therapy were considered 'unable to determine' Test of cure Visit as well. Due to early termination of the study, a Bayesian approach for informal hypothesis testing was not performed.
Measured: Day 5 to 9 post IV therapy
Number of Participants With Microbiological Response in MITT Population
Microbiological Response at End of IV Therapy was assessed as Microbiological Success (MS) or Microbiological Failure (MF). MS was categorized as microbiological eradication (ME) and presumed microbiological eradication (PME). MF was categorized as microbiological persistence (MP), presumed microbiological persistence (PMP), unable to determine, new infection and colonization. Number of participants with microbiological response in MITT population were reported.
Measured: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Microbiological Response in Microbiological Evaluable Population
Microbiological Response at End of IV Therapy was assessed as MS or MF. MS was categorized as ME and PME. MF was categorized as MP and PMP, unable to determine, new infection and colonization. Number of participants with microbiological response in microbiological evaluable population were reported.
Measured: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Clinical Response in Microbiological Evaluable Population
Clinical success was defined as resolution or improvement of Baseline signs and symptoms of cIAI, including white blood cell count within normal limits, participant was afebrile and peritoneal findings consistent with cIAI were no longer present with no new symptoms present that were not present at Baseline and no use of additional or alternate antibiotic therapy. Clinical failure was defined as (1) Lack of improvement or worsening in one or more signs and symptoms of cIAI recorded at Baseline, or reappearance of signs and symptoms that had previously resolved, or (2) signs and symptoms recorded that were not present at Baseline, or (3) receipt of additional or alternate antibiotic therapy for cIAI or (4) participant had died, or (5) participant had an adverse event leading to study drug discontinuation and the participant required additional or alternative antibacterial therapy for the current cIAI.
Measured: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Clinical Response in MITT Population
Clinical success was defined as resolution or improvement of Baseline signs and symptoms of cIAI, including white blood cell count within normal limits, participant was afebrile and peritoneal findings consistent with cIAI were no longer present with no new symptoms present that were not present at Baseline and no use of additional or alternate antibiotic therapy. Clinical failure was defined as (1) Lack of improvement or worsening in one or more signs and symptoms of cIAI recorded at Baseline, or reappearance of signs and symptoms that had previously resolved, or (2) signs and symptoms recorded that were not present at Baseline, or (3) receipt of additional or alternate antibiotic therapy for cIAI or (4) participant had died, or (5) participant had an adverse event leading to study drug discontinuation and the participant required additional or alternative antibacterial therapy for the current cIAI.
Measured: End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)
Number of Participants With Therapeutic Response in Microbiological Evaluable Population
Therapeutic response was a measure of the overall efficacy response, and a therapeutic success referred to participants who had 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. Therapeutic response was determined programmatically.
Measured: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Therapeutic Response in MITT Population
Therapeutic response was a measure of the overall efficacy response, and a therapeutic success referred to participants who had 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. Therapeutic response was determined programmatically.
Measured: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Maximum Plasma Concentration (Cmax) of GSK2251052
Cmax was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for pharmacokinetics (PK) analysis 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
AUC was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis 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
Tmax was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis 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
Cmax was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis was not collected.
Measured: Day 5: 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
AUC was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis was not collected.
Measured: Day 5: 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
Tmax was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis was not collected.
Measured: Day 5: 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
Cmax was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis was not collected.
Measured: Day 5: 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
AUC was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis was not collected.
Measured: Day 5: 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
Tmax was planned to be determined. A nonlinear mixed effects model as implemented in the program NONMEM was planned to be used to analyze plasma concentration data. However, data for PK analysis was not collected.
Measured: Day 5: 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.

3 Oct 20115 Mar 2012

First posted27 Jun 2011 (estimated)
Study start3 Oct 2011
Primary completion5 Mar 2012
Study completion5 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.
Other trials for Infections, IntestinalStudies 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: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01381562
Sponsor's protocol ID: 114689
Status last verified: Oct 2017
First submitted: 9 Jun 2011
Last updated: 29 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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

RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Active, not recruiting
Compassionate-Use of 4% T-EDTA Lock Solution for Central Venous Lines of Pediatric PN Patients
Central Line Complication, Central Line-associated Bloodstream Infection (CLABSI)
RecruitingObservational study
Evaluation, Treatment and Monitoring of Patients With a Known or Suspected Parasitic Infection
Malaria, Intestinal Worms
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections

All Infections, Intestinal trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Assess the Safety, Tolerability and Preliminary Efficacy of GSK2251052 in the Treatment of Complicated Intra-abdominal Infection in Adults
ClinicalTrials.gov ID: NCT01381562
Acronym / sponsor ID: 114689
Conditions: Infections, Intestinal
Keywords: intra-abdominal infection, belly, Gram-negative pathogen, abscess, peritonitis
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Microbiological findings of resistance on therapy in patients with complicated urinary tract infection
Enrolment: 15 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 3 Oct 2011 (actual)
Primary completion: 5 Mar 2012 (actual)
Study completion: 5 Mar 2012 (actual)
First posted: 27 Jun 2011 (estimated)
Results: Posted 29 Nov 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: Drug: GSK2251052, Other: Placeboq12h administered via IV infusion, plus saline placebo
GSK2251052 1500mg	Experimental	Drug: Drug: GSK2251052, Other: Placeboq12h administered via IV infusion, plus saline placebo
Meropenem 1G	Active comparator	Drug: Meropenem, Other: Placeboq8h 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 (38 listed)

Adult subjects least 18 years of age.
N.B. Females of non-childbearing or childbearing potential may be enrolled. It is not contraindicated to enrol females of childbearing potential; however, 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 (31 listed)

Subject has a known or suspected diagnosis of the following:
Abdominal wall abscess
Small bowel obstruction or ischemic bowel disease without perforation
Traumatic bowel perforation with surgery within 12 hours
Perforation of gastroduodenal ulcer with surgery within 24 hours

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
Drug: GSK2251052Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion	Drug	GSK2251052 1500mg, GSK2251052 750mg
MeropenemAlso: Merrem ®, MeronemReconstituted, added to 100mL 0.9% NaCl solution and administered via IV infusion	Drug	Meropenem 1G
Placebosaline placebo	Other	GSK2251052 1500mg, GSK2251052 750mg, Meropenem 1G

Primary outcome

Number of Participants With Any Adverse Event
Time frame: Up to Day 42
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE included AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition
Number of Participants With Clinically Significant Trends in Vital Signs Over the Period of Study Duration
Time frame: Up to Day 42
Vital parameters including systolic and diastolic blood pressure, heart rate, respiration rate, and temperature were recorded. The number of participants with potentially clinically concern value of any vital parameter at any visit were reported.
Number of Participants With Normal and Abnormal ECG Findings
Time frame: Up to Day 42
12-lead ECGs was obtained during the study using an ECG machine and performed with the participant in a semi-supine position rested in this position for at least 10 minutes beforehand. Measurements deviated substantially from previous readings were repeated immediately. Number of participants with normal and abnormal ECG findings were reported.
Laboratory Parameters of Interest- Mean Hemoglobin Over the Period of Study Duration
Time frame: Up to Day 42
Absolute mean hemoglobin values recorded over the period of duration were reported.
Laboratory Parameters of Interest- Mean Reticulocytes Over the Period of Study Duration
Time frame: Up to 42 days
Absolute mean reticulocytes values recorded over the period of duration were reported.
Mean Change From Baseline in Hemoglobin for Partcipants With Significant Hemoglobin Drop
Time frame: Baseline (Day 1) and up to Day 42
Participants in whom the hemoglobin level dropped by more than 30% from Baseline that was not attributable to acute blood loss were recorded and immediately withdrawn from study treatment. Baseline assessments were recorded on Visit 1 (Day 1) and used as Baseline values. The change from Baseline was calculated by subtracting the Baseline values from Day 42 values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing. The mean change from Baseline in hemoglobin for participants with significant hemoglobin drop were reported.
Number of Participants With Clinical Response at Test of Cure Visit (5-9 Days Post-therapy) in Microbiological Intent to Treat (MITT) Population
Time frame: Day 5 to 9 post IV therapy
Test of cure-clinical success was resolution of signs and symptoms of complicated intra-abdominal infection (cIAI) for participants who were clinical successes at the end of IV therapy visit with no new symptoms recorded that were not present at Baseline and no use of additional antibiotic therapy for cIAI. Test of cure-clinical failure was persistence of signs and symptoms of cIAI recorded at Baseline, or reappearance of signs and symptoms that had previously resolved, or new signs and symptoms recorded that were not present at a previous visit, or receipt of additional or alternate antibiotic therapy for cIAI or participant had died. Test of cure- unable to determine was refusal to consent to a clinical examination, lost to follow-up. Participants who were 'unable to determine' at End of IV therapy were considered 'unable to determine' Test of cure Visit as well. Due to early termination of the study, a Bayesian approach for informal hypothesis testing was not performed.

16 secondary outcomes

Number of Participants With Clinical Response at Test of Cure Visit (5-9 Days Post-therapy) in Microbiological Evaluable Population.
Time frame: Day 5 to 9 post IV therapy
Number of Participants With Microbiological Response in MITT Population
Time frame: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Microbiological Response in Microbiological Evaluable Population
Time frame: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Clinical Response in Microbiological Evaluable Population
Time frame: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Clinical Response in MITT Population
Time frame: End of IV therapy (0-24 hours post-therapy) and Late Follow-up (21-28 days post-therapy)
Number of Participants With Therapeutic Response in Microbiological Evaluable Population
Time frame: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); Late Follow-up (21-28 days post-therapy)
Number of Participants With Therapeutic Response in MITT Population
Time frame: End of IV therapy (0-24 hours post-therapy); Test of cure (5-9 days post-therapy); 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 5: 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 5: 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 5: 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 5: 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 5: 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 5: 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 29 Nov 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	5	5
GSK2251052 1500 mg	4	3
Meropenem 1.0 g	5	5

Primary outcome: Number of Participants With Any Adverse Event

Time frame: Up to Day 42. Count of participants. Unit: Participants

Measure	GSK2251052 750 mg n = 5	GSK2251052 1500 mg n = 4	Meropenem 1g n = 5
Any AE	5	4	3
Any SAE	2	3	0

Population analysed: Safety Population comprised of all participants who received at least one dose of study medication.

Primary outcome: Number of Participants With Clinically Significant Trends in Vital Signs Over the Period of Study Duration

Time frame: Up to Day 42. Count of participants. Unit: Participants

Measure	GSK2251052 750 mg n = 5	GSK2251052 1500 mg n = 4	Meropenem 1g n = 5
Value	0	0	0

Population analysed: Safety Population.

Primary outcome: Number of Participants With Normal and Abnormal ECG Findings

Time frame: Up to Day 42. Count of participants. Unit: Participants

Measure	GSK2251052 750 mg n = 5	GSK2251052 1500 mg n = 4	Meropenem 1g n = 5
Baseline, Pre-dose 1, Normal	4	4	4
Baseline, Pre-dose 1, Unable to evaluate	0	0	1
Baseline, Pre-dose 1, Abnormal	1	0	0
Baseline, Pre-dose 2, Normal	4	4	5
Baseline, Pre-dose 2, Abnormal	1	0	0
Baseline, Pre-dose 3, Normal	4	4	5
Baseline, Pre-dose 3, Abnormal	1	0	0
Baseline, Post-dose , Normal	4	3	4

Population analysed: Safety population.

Primary outcome: Laboratory Parameters of Interest- Mean Hemoglobin Over the Period of Study Duration

Time frame: Up to Day 42. Mean (Standard Deviation). Unit: Gram per Litre

Measure	GSK2251052 750 mg n = 5	GSK2251052 1500 mg n = 4	Meropenem 1g n = 5
Baseline (Day 1)	142.2 (8.76)	121.5 (12.23)	125.0 (14.85)
On IV Therapy (Day 3)	134.4 (13.61)	112.3 (16.30)	137.3 (19.64)
On IV Therapy (Day 5)	127.2 (14.79)	120.7 (11.02)	131.0 (18.63)
On IV Therapy (Day 8)	148.0 (NA)	132.0 (NA)	143.0 (NA)
On IV Therapy (Day 11)	97.0 (NA)	–	–
End Of IV Therapy	126.2 (23.35)	123.8 (9.88)	130.8 (20.22)
Haematology Safety	131.4 (15.21)	118.0 (9.93)	138.6 (14.72)
Test of cure	131.0 (25.26)	116.0 (5.77)	138.2 (11.52)

Population analysed: Safety population.

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were reported up to Late Follow-up visit (Day 42). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GSK2251052 750 mg	2 of 5 (40%)	4 of 5 (80%)	0 of 5
GSK2251052 1500 mg	3 of 4 (75%)	4 of 4 (100%)	0 of 4
Meropenem 1g	0 of 5 (0%)	3 of 5 (60%)	0 of 5

Limitations and caveats (from the sponsor): This study was terminated early because only 15 participants were enrolled.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Infections, Intestinal

RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Active, not recruiting
Compassionate-Use of 4% T-EDTA Lock Solution for Central Venous Lines of Pediatric PN Patients
Central Line Complication, Central Line-associated Bloodstream Infection (CLABSI)
RecruitingObservational study
Evaluation, Treatment and Monitoring of Patients With a Known or Suspected Parasitic Infection
Malaria, Intestinal Worms
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections

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

31 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Drug: GSK2251052 and Meropenem in people with Infections, Intestinal, run by GlaxoSmithKline at 31 sites in 7 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 38 inclusion and 31 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 29 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Russia, Canada, Spain, France and 2 more countries. 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 29 Nov 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?

Number of Participants With Any Adverse Event (time frame: Up to Day 42). The study lists 7 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 NCT01381562.

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 29 Nov 2017.