Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections

This study has been completed.
Sponsor:
Information provided by:
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01147640
First received: June 17, 2010
Last updated: May 5, 2011
Last verified: May 2011
  Purpose

A Phase 2, multicenter, prospective, randomized, double-blind study of CXA-101/ tazobactam (1000/500 mg q8h) and metronidazole (500 mg q8h) IV infusion vs. meropenem IV infusion (1000 mg q8h) and a matching saline placebo (q8h) in the treatment of cIAI in adult subjects. Dose adjustments for subjects with mild renal impairment are not necessary and subjects with more severe degrees of renal failure are excluded.


Condition Intervention Phase
Complicated Intra-abdominal Infection
Drug: CXA-101/ tazobactam and metronidazole
Drug: meropenem plus saline placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-Blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA 101/ Tazobactam and Metronidazole With That of Meropenem in Complicated Intraabdominal Infections

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • clinical response of CXA 101/tazobactam and metronidazole [ Time Frame: Test-of-Cure Visit (7-14 days after EOT) ] [ Designated as safety issue: No ]
    Clinical response of CXA 101/ tazobactam and metronidazole and that of meropenem in the treatment of hospitalized subjects with cIAI at the TOC visit


Secondary Outcome Measures:
  • microbiological response of CXA 101/tazobactam and metronidazole [ Time Frame: Test-of-Cure Visit (7-14 days post EOT) ] [ Designated as safety issue: No ]
    Determine the microbiological response of CXA 101/ tazobactam and metronidazole and that of meropenem

  • assess safety of CXA 101/ tazobactam and metronidazole [ Time Frame: every visit ] [ Designated as safety issue: Yes ]
    Describe the safety profile of CXA 101/ tazobactam and metronidazole

  • Evaluate the PK of CXA 101/ tazobactam [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    Evaluate the PK of CXA 101/ tazobactam


Estimated Enrollment: 120
Study Start Date: June 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CXA 101/tazobactam and metronidazole Drug: CXA-101/ tazobactam and metronidazole
CXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion
Active Comparator: meropenem with matching saline placebo Drug: meropenem plus saline placebo
meropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, from 18 to 90 years of age, inclusive
  • One of the following diagnoses (in which there is evidence of intraperitoneal infection) including:(a) Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall;(b)Diverticular disease with perforation or abscess; (c) Appendiceal perforation or periappendiceal abscess; (d) Acute gastric or duodenal perforation, only if operated on >24 hours after perforation occurs; (e) Traumatic perforation of the intestine, only if operated on > 12 hours after perforation occurs; (f) Peritonitis due to perforated viscus, postoperative or spread from other focus of infection (but not spontaneous [primary] bacterial peritonitis or peritonitis associated with cirrhosis and chronic ascites).Subjects with inflammatory bowel disease or ischemic bowel disease are eligible provided there is bowel perforation; or (g) Intraabdominal abscess (including liver and spleen).
  • Subject requires surgical intervention (e.g. laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of (before or after) the first dose of study drug
  • If subject is to be enrolled preoperatively, the subject must have radiographic evidence of bowel perforation or intraabdominal abscess
  • Subjects who failed prior antibacterial treatment for the current cIAI can be enrolled but must: (a) have a positive culture (from an intraabdominal site) and (b) require surgical intervention. Such subjects can be enrolled before the results of the culture are known; however, if the culture is negative, study drug administration must be discontinued.
  • Willing and able to comply with all study procedures and restrictions
  • Willing and able to provide written informed consent

Exclusion Criteria:

  • Women who are pregnant, nursing, or - if of child bearing potential - not using a medically accepted, effective method of birth control (e.g. condom, oral contraceptive, indwelling intrauterine device, or sexual abstinence)
  • Diagnosis of 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 (these are considered situations of peritoneal soiling before infection has become established); another intraabdominal process in which the primary etiology is not likely to be infectious.
  • Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected, necrotizing pancreatitis, or pancreatic abscess
  • cIAI managed by staged abdominal repair (STAR), open abdomen technique or any situation where infection source control is not likely to be achieved
  • Known prior to randomization to have an IAI or postoperative infection caused by pathogen(s) resistant to meropenem
  • Considered unlikely to survive the 4- to 5-week study period
  • Any rapidly-progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure and septic shock)
  • The need for concomitant systemic antibacterial agents (other than vancomycin or linezolid) in addition to study drug(s)
  • Moderate or severe impairment of renal function (estimated CrCl < 50 mL/min), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours)
  • The presence of hepatic disease defined as: (a) ALT or AST > 4 x ULN; (b)Total bilirubin >2 x ULN, unrelated to cholecystitis (c) Alkaline phosphatase >4 x ULN. Subjects with a value >4 x ULN and <5 x ULN are eligible if this value is historically stable.
  • Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure
  • Hematocrit < 25% or hemoglobin < 8 gm/dL
  • Neutropenia with absolute neutrophil count < 1000/mm3
  • Platelet count < 75,000 /mm3. Subjects with a platelet count as low as 50,000 /mm3 are permitted if the reduction is historically stable.
  • Immunocompromising illness, including known human immunodeficiency virus (HIV) positivity or AIDS, organ (including bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroid therapy (e.g. >40 mg prednisone or equivalent per day for greater than 2 weeks).
  • History of hypersensitivity reactions to cephalosporins, carbapenems, penicillins, ß-lactamase inhibitors, metronidazole, or nitroimidazole derivatives. Subjects with a history of mild skin rash, not documented to be caused by previous ß-lactam use, may be enrolled.
  • Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data
  • Clinically significant abnormality in baseline electrocardiogram (ECG)
  • Participation in any investigational drug or device study within 30 days prior to study entry
  • Use of systemic antibiotic therapy for IAI for 24 or more hours in the 48-hour period prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
  • More than one dose of an active non-study antibacterial regimen was given postoperatively. For subjects enrolled preoperatively, no postoperative non-study antibacterial therapy is allowed
  • who previously participated in a study with CXA-101
  • Subjects who previously received imipenem, meropenem, doripenem or cefepime for the current intraabdominal infection
  • Subjects who have received disulfiram in the past 14 days or who are currently receiving probenecid.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147640

  Show 33 Study Locations
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Ian Friedland, MD Cubist Pharmaceuticals
  More Information

No publications provided by Cubist Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ed Campanaro/Vice President, Clinical Operations and Data Management, Cubist Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01147640     History of Changes
Other Study ID Numbers: CXA-IAI-10-01
Study First Received: June 17, 2010
Last Updated: May 5, 2011
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health
Georgia: Ministry of Health
Russia: Ethics Committee
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
Serbia: Ethics Committee

Additional relevant MeSH terms:
Communicable Diseases
Infection
Intraabdominal Infections
Meropenem
Metronidazole
Tazobactam
Anti-Bacterial Agents
Anti-Infective Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014