Complicated urinary tract infection (cUTI), acute uncomplicated pyelonephritis (AP), hospital acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and complicated intra-abdominal infection (cIAI) MedDRA version: 21.0 Level: LLT Classification code 10080628 Term: Complicated urinary tract infection System Organ Class: 100000004862 MedDRA version: 20.1 Level: LLT Classification code 10079985 Term: Uncomplicated pyelonephritis System Organ Class: 100000004862 Me
Conditions
Sponsors
Meiji Seika Pharma Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who meet all of the following criteria will be eligible to participate in the study: 1. Male or female patients = 18 years of age (or age of legal consent, whichever is older) at the time of obtaining informed consent and who can be hospitalized throughout the Treatment Period; 2. Weight = 140 kg; 3. The following criteria must be satisfied: a. For known CRE infection, meets either of the following (i or ii): i. Has a known CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence from CRE culture, susceptibility testing, and possible carbapenemase phenotypic testing (or possible molecular testing) within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; AND Has received no more than 24 hours of an antimicrobial agent to which the known CRE is known to be susceptible within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug of the study drug; OR ii. Has a known CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence from CRE culture, susceptibility testing, and possible carbapenemase phenotypic testing (or molecular testing ) within 72 hours (or 96 hours for cIAI) prior to the first dose of the study drug; AND Has documented clinical evidence of failure (ie, clinical deterioration or failure to improve) after at least 48 hours of treatment with an antimicrobial agent to which the known CRE is known to be susceptible within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; b. For suspected CRE infection, meets the following (i or ii): i. Has a suspected CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence which may be determined within 90 days prior to the first dose of study drug through rapid diagnostic tests, active surveillance cultures, other documentation of CRE colonization, or prior infection due to a CRE pathogen; AND Has received no more than 24 hours of empiric antimicrobial therapy for Gram-negative organisms within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; OR ii. Has a suspected CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence which may be determined within 90 days prior to the first dose of study drug through rapid diagnostic tests, active surveillance cultures, other documentation of CRE colonization, or prior infection due to a CRE pathogen; AND Has documented clinical evidence of failure (ie, clinical deterioration or failure to improve) after at least 48 hours of treatment with empiric antimicrobial therapy for Gram-negative organisms within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; Note: CRE is defined as Enterobacterales by susceptibility data of minimum inhibitory concentration (MIC) = 2 µg/mL to imipenem or meropenem OR imipenem or meropenem disk diffusion (zone diameter < 22 mm). If MIC or disk diffusion data are not available in the local laboratory or before the availability of MIC or disk diffusion results, each site can use other susceptibility testing and criteria in the institution as the initial evidence of CRE for enrollment. In any case, pathogen identification and susceptibility testing performed at the central laboratory will be used to determine CRE in the final study analysis. Note: Complete list of inclusion criteria is in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from participation in the study: 1. Has a history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious allergic reaction to carbapenems, cephems, penicillins, other B-lactam antibiotics, or any B-lactamase inhibitors (eg, tazobactam, sulbactam, or clavulanic acid); 2. Has known or suspected single or concurrent infection with Acinetobacter spp., metallo-ßlactamase (MBL) producing Pseudomonas aeruginosa, or other organisms that are not adequately covered by the study drug (eg, concurrent viral, mycobacterial, or fungal infection) and need to be managed with other anti-infectives; Note: Patients with qualifying Gram-negative pathogen co-infected with a Gram-positive pathogen may be administered narrow spectrum, open-label glycopeptide (eg, vancomycin), oxazolidinone (eg, linezolid), or daptomycin concomitantly with the study drug at the discretion of the Investigator. Patients with cIAI may receive metronidazole in addition to cefepime/nacubactam, aztreonam/nacubactam, or as part of best available therapy (BAT) if anaerobic coverage is deemed necessary. 3. Has only a Gram-positive organism pathogen isolated from study-qualifying culture; Note: Complete list of exclusion criteria is in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint is the proportion of patients with overall treatment success at TOC across all infection types (ie, cUTI, AP, HABP, VABP, and cIAI), which is a composite endpoint derived from the efficacy outcomes of each infection type. This is the proportion of patients in the Microbiological CRE Modified Intent-to-Treat (mCRE-MITT) Population with a treatment outcome of success. ;Timepoint(s) of evaluation of this end point: Assessment of - Clinical Signs and Symptoms - Clinical Outcome: at EA, EOT, TOC, FUP, and ET - Microbiology assessments: Urine Culture: at Screening, prior to study drug administration on Day 1, EA, EOT, TOC, FUP (if clinically indicated), and ET. Blood Culture: at Screening and prior to randomization on Day 1 Intra-abdominal cultures: during the time of surgical (or percutaneous) intervention (cIAI patients). Specimen collection as per Protocol Respiratory tract specimens: taken within 72 hours prior to first dose of study drug Other culture samples: within 72 hours prior to first dose of study drug (if a tissue sample (ie, kidney biopsy, lung biopsy) is collected) - Composite Clinical Outcome of Cure and Microbiological Outcome of Eradication: at EA, EOT, TOC, FUP, and ET ;Main Objective: The primary objectives of this study are the following: - To assess the efficacy of cefepime/nacubactam and aztreonam/nacubactam administered by intravenous (IV) infusion using the composite endpoint of overall treatment success across all infection types (ie, cUTI, AP, HABP, VABP, and cIAI) due to carbapenem-resistant Enterobacterales (CRE); and - To assess the safety of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion. ;Secondary Objective: The secondary objectives of this study are the following: - To assess the efficacy of cefepime/nacubactam and aztreonam/nacubactam administered by IV infusion in patients with secondary bacteremia due to each infection type (ie, cUTI, AP, HABP, VABP, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints across all infection types, for individual infection type and across all infection types, for c,UTI/AP only, for HABP/VABP only, or cIAI only, for secondary bacteremia only are included in study protocol;Timepoint(s) of evaluation of this end point: Assessments at EA, EOT, TOC, and the FUP (at different timepoints for the secondary efficacy endpoints) | — |
Countries
China, Croatia, Czechia, France, Georgia, Greece, Israel, Italy, Japan, Latvia, Malaysia, Slovakia, Spain, Taiwan, Thailand, Turkey
Contacts
Public ContactClinical Trial Management
Medpace, Inc.
Outcome results
None listed