GSK2251052 in the Treatment of Complicated Intra-abdomina... | NCT01381562

Label	Type	Description	Intervention Names
GSK2251052 750mg	Experimental	q12h administered via IV infusion, plus saline placebo	Drug: Drug: GSK2251052 Other: Placebo
GSK2251052 1500mg	Experimental	q12h administered via IV infusion, plus saline placebo	Drug: Drug: GSK2251052 Other: Placebo
Meropenem 1G	Active Comparator	q8h administered via IV infusion, plus saline placebo	Drug: Meropenem Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Drug: GSK2251052	Drug	Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion	GSK2251052 1500mg GSK2251052 750mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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.	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.	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.	Up to Day 42
Laboratory Parameters of Interest- Mean Reticulocytes Over the Period of Study Duration

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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,
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

Exclusion Criteria:

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.
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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Mobile	Alabama	36617	United States
GSK Investigational Site

ID	Title	Description
FG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 millilitre (mL) saline solution as intravenous (IV) infusion administered over 60 minutes, twice a day (BID) and meropenem matching placebo solution, 100 ml, administered over 30 minutes, thrice a day (TID) from Day 2 to Day 14 of the study.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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

Posted

Count of Participants

Participants

Up to Day 42

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.

Units	Counts
Participants	OG0005 OG0014 OG0025

Title

Denominators

Categories

Any AE

Title	Measurements
	OG0005 OG0014 OG0023

Any SAE

Primary

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.

Safety Population.

Posted

Count of Participants

Participants

Up to Day 42

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.

Primary

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.

Safety population.

Posted

Count of Participants

Participants

Up to Day 42

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.

Primary

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

Absolute mean hemoglobin values recorded over the period of duration were reported.

Safety population.

Posted

Mean

Standard Deviation

Gram per Litre

Up to Day 42

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.

Primary

Laboratory Parameters of Interest- Mean Reticulocytes Over the Period of Study Duration

Absolute mean reticulocytes values recorded over the period of duration were reported.

Safety population.

Posted

Mean

Standard Deviation

Trillion cells per Litre

Up to 42 days

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.

Primary

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.

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

Posted

Mean

Standard Deviation

grams/L

Baseline (Day 1) and up to Day 42

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Primary

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.

MITT Population comprised of all randomized participants who received at least one dose of study medication and had at least one Gram-negative pathogen identified at Baseline. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Day 5 to 9 post IV therapy

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Secondary

Number of Participants With Clinical Response at Test of Cure Visit (5-9 Days Post-therapy) in Microbiological Evaluable Population.

Microbial evaluation population comprised of participants from the MITT population who adhered to the protocol (do not violate the protocol) and received at least 5 days of IV therapy.

Posted

Count of Participants

Participants

Day 5 to 9 post IV therapy

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Secondary

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.

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

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Secondary

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.

Microbiological evaluable population. Only those participants available at the specified time points were analyzed

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g

Secondary

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.

Microbiological evaluable population. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001

Secondary

Number of Participants With Clinical Response in MITT Population

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg

Secondary

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.

Microbiological evaluable population. Only those participants available at the specified time points were analyzed.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002

Secondary

Number of Participants With Therapeutic Response in MITT Population

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

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG002	Meropenem 1g

Secondary

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.

PK population consisted of participants for whom PK samples were collected. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts

Secondary

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.

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

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.

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

Cmax of GSK2251052 Using Non-intensive PK Sampling

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

AUC of GSK2251052 Using Non-intensive PK Sampling

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

Tmax of GSK2251052 Using Non-intensive PK Sampling

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

Cmax of GSK2251052 Using Intensive PK Sampling

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

AUC of GSK2251052 Using Intensive PK Sampling

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Secondary

Tmax of GSK2251052 Using Intensive PK Sampling

PK population. Data for PK analysis was not collected.

Posted

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

ID	Title	Description
OG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
OG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected4 at risk EG0021 affected5 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected4 at risk EG0021 affected5 at risk
Infusion site pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Incision site infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Pelvic abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Peritoneal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Electrocardiogram ST segment elevation	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Platelet count decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Platelet count increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Reticulocyte count increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Sinus bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Dyssomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Anisocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Poikilocytosis	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk
Pollakiuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Electrocardiogram repolarisation abnormality	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0010 affected4 at risk EG0021 affected5 at risk

ID	Term
D007239	Infections
D059413	Intraabdominal Infections
D000038	Abscess
D010538	Peritonitis

ID	Term
D013492	Suppuration
D007249	Inflammation
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D010532	Peritoneal Diseases
D004066	Digestive System Diseases

ID	Term
D013845	Thienamycins
D015780	Carbapenems
D047090	beta-Lactams
D007769	Lactams
D000577	Amides
D009930	Organic Chemicals
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
BG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.
BG002	Meropenem 1 g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GSK2251052 750 mg	Eligible participants received GSK2251052, 750 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem matching placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.	5	2	5	4	5
EG001	GSK2251052 1500 mg	Eligible participants received GSK2251052, 1500 mg, in 200 or 250 mL saline solution as IV infusion administered over 60 minutes, BID and meropenem placebo solution, 100 ml, administered over 30 minutes, TID from Day 2 to Day 14 of the study.	4	3	4	4	4
EG002	Meropenem 1g	Eligible participants received meropenem, 1.0 g, in 100 ml saline solution as IV infusion administered over 30 minutes TID and two doses of GSK2251052 matching placebo saline solution, 200 or 250 ml, administered over 60 minutes, BID from Day 2 to Day 14 of the study.	5	0	5	3	5

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0012 affected4 at risk EG0020 affected5 at risk
Pelvic abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected5 at risk EG0010 affected4 at risk EG0020 affected5 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected5 at risk EG0011 affected4 at risk EG0020 affected5 at risk

ID	Term
C583949	3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole
D000077731	Meropenem