GSK2251052 in the Treatment of Complicated Intra-abdominal Infections

NCT01381562 | Terminated Phase 2 Results DMC

• 1 other identifier: 114689
• Study Type: interventional
• Target: 15
• Locations: 7 countries
• Sites: 31

Brief 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. GSK2251052 has a spectrum of microbiological activity that includes pathogens responsible for cIAI.

Conditions

Infections, Intestinal

Keywords

intra-abdominal infection; belly; Gram-negative pathogen; abscess; peritonitis

Outcome Measures

Primary Outcomes (7)

• 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

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

  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.

  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.

  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.

  Day 5 to 9 post IV therapy

• Number of Participants With Microbiological Response in MITT Population

  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

  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

  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

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

Study Arms (3)

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

Interventions

Drug: GSK2251052 DRUG

Reconstituted, added to 250mL 0.9% NaCl solution and administered via IV infusion

GSK2251052 1500mg; GSK2251052 750mg

Meropenem DRUG

Reconstituted, added to 100mL 0.9% NaCl solution and administered via IV infusion

Also known as: Merrem ®, Meronem

Meropenem 1G

Placebo OTHER

saline placebo

GSK2251052 1500mg; GSK2251052 750mg; Meropenem 1G

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (31)

GSK Investigational Site

Mobile, Alabama, 36617, United States

Location

GSK Investigational Site

Long Beach, California, 90822, United States

Location

GSK Investigational Site

Torrance, California, 90509, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32209, United States

Location

GSK Investigational Site

Council Bluffs, Iowa, 51503, United States

Location

GSK Investigational Site

Topeka, Kansas, 66604, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70112, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89109, United States

Location

GSK Investigational Site

Buffalo, New York, 14215, United States

Location

GSK Investigational Site

Columbus, Ohio, 43215, United States

Location

GSK Investigational Site

Lima, Ohio, 45801, United States

Location

GSK Investigational Site

Richmond, Virginia, 23298, United States

Location

GSK Investigational Site

Chicoutimi, Quebec, G7H 5H6, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

GSK Investigational Site

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

GSK Investigational Site

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

GSK Investigational Site

Prague, 100 34, Czechia

Location

GSK Investigational Site

Prague, 10034, Czechia

Location

GSK Investigational Site

Limoges, 87042, France

Location

GSK Investigational Site

Nîmes, 30029, France

Location

GSK Investigational Site

Strasbourg, 67200, France

Location

GSK Investigational Site

Verona, Veneto, 37134, Italy

Location

GSK Investigational Site

Irkutsk, 664079, Russia

Location

GSK Investigational Site

Perm, 614036, Russia

Location

GSK Investigational Site

Perm, 614068, Russia

Location

GSK Investigational Site

Saint Petersburgh, 192242, Russia

Location

GSK Investigational Site

Smolensk, 214019, Russia

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Elche (Alicante), 03203, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Pama de Mallorca, 07010, Spain

Location

MeSH Terms

Conditions

Infections; Intraabdominal Infections; Abscess; Peritonitis

Interventions

3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole; Meropenem

Condition Hierarchy (Ancestors)

Suppuration; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peritoneal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was terminated early because only 15 participants were enrolled.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 27, 2011
• Study Start: October 3, 2011
• Primary Completion: March 5, 2012
• Study Completion: March 5, 2012
• Last Updated: November 29, 2017
• Results First Posted: November 29, 2017

Record last verified: 2017-10

Locations

US (12); CZ (2); CA (4); FR (3); IT (1); ES (4); RU (5)