determine the PK and safety and tolerability of ATM-AVI for the treatment of cIAIs in hospitalized adults - REJUVENATE

Exclusion Criteria

• 1. Involvement in the planning and/or conduct of the study
• 2. Patient has been previously enrolled in this study, previously treated
• with ATM-AVI or previously participated in an investigation study
• containing AVI
• 3. Patient has participated or intends to participate in any other clinical
• study that involves the administration of an investigational medication
• at the time of presentation, during the course of the study, or during the
• 30 days prior to study start.
• 4. Patient has a history of serious allergy, hypersensitivity (eg,
• anaphylaxis), or any serious reaction to aztreonam, carbapenem,
• monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the respective (investigational) medicinal products to be administered during the study
• 5. Patient has a diagnosis of abdominal wall abscess; small bowel
• obstruction or ischemic bowel disease without perforation; traumatic
• bowel perforation with surgery within 12 hours of diagnosis; perforation of
• gastroduodenal ulcer with surgery within 24 hours of diagnosis (these are considered
• situations of peritoneal soiling before infection has become established);
• another intra-abdominal process in which the primary etiology is not
• likely to be infectious
• 6. Patient has a simple cholecystitis, gangrenous cholecystitis without
• rupture, simple appendicitis, acute suppurative cholangitis, infected
• necrotizing pancreatitis, pancreatic abscess or ischaemic/necrotic
• intestine without perforation
• 7. Patient has a cIAI managed by staged abdominal repair (STAR), open abdomen technique or any situation where infection source control is not likely to be achieved or in whom the abdomen is left open, particularly
• those for whom re-operation is planned, or those unlikely to solely
• respond to antimicrobial therapy
• 8. At screening, if it is known the patient has an infection due to a
• pathogen that is unlikely to respond to ATM-AVI plus metronidazole
• treatment
• 9. Patient has a rapidly progressive (expected to die in <30 days) or
• terminal illness, including acute hepatic failure, respiratory failure or
• septic shock with a high risk of mortality due to other causes than cIAI
• 10. Patient has received systemic antibacterial agents within the 72-
• hour period prior to study entry, unless either of the following pertains:
• (a) Patient has a new infection (not considered a treatment failure) and
• the following is met:
• - Patient received no more than 24 hours within the 72 hour period prior to study entry
• (b) Patient is considered to have failed the previous treatment regimen
• 11. Patient has a concurrent infection that may interfere with the
• evaluation of clinical cure for the study therapy
• 12. Patient needs effective concomitant systemic antibacterials (oral,
• IV, or intramuscular) or antifungals in addition to the investigational
• product and metronidazole
• 13. Patient has creatinine clearance ≤50 ml/min. Note: following
• review of PK and safety data from the first 10 enrolled patients, and the
• confirmation of a provisional dose schedule, patients with a creatinine
• clearance of 31 – 50 mL/min may be included.
• 14. Patient has had acute hepatitis in the prior 6 months, chronic
• hepatitis, cirrhosis (any Child-Pugh class), acute hepatic failure, or acute
• decompensation of chronic hepatic failure
• 15. Presence of hepatic disease as indicated by aspartate
• aminotransferase (AST) or alanine transaminase (ALT) >3 × upper limit
• of normal (ULN) at Screening. Patients with AST and/or ALT >3 × ULN
• and < 5 × ULN are eligible if these elevations are acute, not
• accompanied by a total bilirubin ≥ 2xULN and documented by the
• investigator as being directly related to the infectious process being
• treated
• 16. Patient has a total bilirubin >3 × ULN, unless isolated
• hyperbilirubinemia is directly related to the acute infection or due to
• known Gilbert's disease
• 17. Alkaline phosphatase (ALP) >3 × ULN. Patients with values >3 ×
• ULN and <5 x ULN are eligible if this value is acute and directly related
• to the infectious process being treated.
• 18. Patients with an immunocompromising illness
• 19. Known active Clostridium difficile associated diarrhoea
• 20. Any other condition that, in the opinion of the investigator, may
• confound the results of the study or pose additional risks
• 21. Patient with a do not resuscitate order
• 22. Patient has an absolute neutrophil count <1000/μL
• 23. Patient has a hematocrit <25% or hemoglobin <8 gm/dL.
• 24. Patient has a platelet count <75,000/μL. Patients with a platelet as
• low as 50,000 /μL are permitted if the reduction is historically stable
• 25. Patient is currently receiving treatment with probenecid.
• 26. Patient is pregnant or breastfeeding or if of child bearing potential,
• 27. Patient is unlikely to comply with protocol,
• 28. Patient is currently receiving anti-convulsant therapy to prevent
• recurrence of a past history of seizures.
• 29. Patient has a prior liver, pancreas or small-bowel transplant.