A trial to test a new antibiotic given by vein to be used for Complicated Intra-abdominal infections.

• Conditions: Complicated Intraabdominal Infections; MedDRA version: 14.1Level: LLTClassification code 10056570Term: Intra-abdominal infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2011-002119-27-LT
• Lead Sponsor: Cubist Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10-31
• Last Update Posted: 21 October 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 906

Inclusion Criteria

1. Provide written informed consent prior to any study-related procedure not part of normal medical care (a legally acceptable representative may provide consent if the subject is unable to do so, provided this is approved by local country and institution specific guidelines)
2. Be males or females = 18 years of age.
3. If female, subject is non-lactating, and is either:
a. Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or
b. Of childbearing potential and is practicing a barrier method of birth control (e.g., a diaphragm or contraceptive sponge) along with 1 of the following methods: oral or parenteral contraceptives (oral or parenteral contraceptives must have been used for at least 3 months prior to study drug administration), or a vasectomized partner. Or the subject is practicing abstinence from sexual intercourse. Subjects must be willing to practice these methods for the duration of the trial and for at least 35 days after last dose of study medication.
4. Males are required to practice reliable birth control methods (condom or other barrier device) during the conduct of the study and for at least 35 days after last dose of study medication.
5. 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 other perforated viscus or following a prior operative procedure;
i. Subjects with inflammatory bowel disease or ischemic bowel disease are eligible provided there is bowel perforation.
g. Intraabdominal abscess (including liver or spleen).
6. 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.
7. If subject is to be enrolled preoperatively, the subject should have radiographic evidence of bowel perforation or intraabdominal abscess.
8. 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.
9. Willing and able to comply with all study procedures and restrictions.
10. Evidence of systemic infection including one or more of the following:
a. Temperature (oral) greater than 38 °C or less than 35 °C;
b. Elevated WBC (>10,500/mm3);
c. Abdominal pain, flank pain, or pain likely due to cIAI that is referred to another anatomic area such as back or hip; or
d. Nausea or vomiting.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 680
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 226

Exclusion Criteria

1. Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation.
2. Simple appendicitis; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; or pelvic infections.
3. Spontaneous [primary] bacterial peritonitis associated with cirrhosis and chronic ascites.
4. Complicated intraabdominal infection managed by staged abdominal repair (STAR), open abdomen technique including temporary closure of the abdomen, or any situation where infection source control is not likely to be achieved.
5. Known prior to randomization to have an IAI or postoperative infection caused by pathogen(s) resistant to meropenem.
6. Use of systemic antibiotic therapy for IAI for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy.
7. More than one dose of an active non-study antibacterial regimen given postoperatively. For subjects enrolled preoperatively, no postoperative non-study antibacterial therapy is allowed.
8. Subjects who previously received imipenem, meropenem, doripenem or cefepime for the current intraabdominal infection.
9. Have a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to IV study drug therapy. (Drugs with only gram-positive activity [e.g., daptomycin, vancomycin, linezolid] are allowed).
10. Severe impairment of renal function (estimated creatinine clearance [CrCl] < 30 mL/min), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours).
11. The presence of hepatic disease at baseline as defined by any of the following:
a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 4 x upper limit of normal (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
d. Acute or chronic hepatitis, cirrhosis, acute hepatic failure, acute decompensation of chronic hepatic failure.
12. Hematocrit < 25% or hemoglobin < 8 gm/dL.
13. Neutropenia with absolute neutrophil count < 1000 /mm3.
14. Platelet count < 75,000 /mm3. Subjects with a platelet count as low as 50,000 /mm3 are permitted if the reduction is historically stable.
15. Considered unlikely to survive the 4- to 5-week study period.
16. Any rapidly-progressing disease or immediately life-threatening illness (including respiratory failure and septic shock).
17. Immunocompromising condition, including established Acquired Immune Deficiency Syndrome (AIDS), hematological malignancy, or bone marrow transplantation, or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, or the administration of corticosteroids equivalent to or greater than 40 mg of prednisone per day administered continuously for more than 14 days preceding randomization.
18. Have a documented history of any moderate or severe hypersensitivity or allergic reaction to any ß-lactam antibacterial (a history of a mild rash followed by uneventful re-exposure is not a
contraindication to enrollment), including cephalosporins, carbapenems, penicillins, or ß-lactamase inhibitors, or metronidazole, or nitroimidazole derivatives.
19. Any condition or circumstance that, in the opinion of the Investigator, would compromise the saf

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified