cUTI, AP, HABP, VABP, cIAI OP0595, nacubactam, CRE
Conditions
Interventions
Patients will receive either cefepime 2 g/nacubactam 1 g or aztreonam 2 g/nacubactam 1 g every 8 hours (plus or minus 1 hour) for at least 5 days and up to 14 days or BAT, if CrCl is at least 60 and l
Sponsors
Suwada Keisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients at least 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 at most140 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 based on evidence from CRE culture and susceptibility testing or other phenotypic or molecular testing within 72 hours (or 96 hours for cIAI) prior to the first dose, alone or as a single isolate of a polymicrobial infection; 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; OR ii. Has a known CRE infection based on evidence from CRE culture and susceptibility testing or other phenotypic or molecular testing within 72 hours (or 96 hours for cIAI) prior to the first dose, alone or as a single isolate of a polymicrobial infection; 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; b. For suspected CRE infection, meets the following (i or ii): i. Has a suspected CRE infection based on evidence from CRE culture and susceptibility testing or other phenotypic or molecular testing, alone or as a single isolate of a polymicrobial infection, from any source within 90 days prior to Day 1; 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; OR ii. Has a suspected CRE infection based on evidence from CRE culture and susceptibility testing or other phenotypic or molecular testing, alone or as a single isolate of a polymicrobial infection, from any source within 90 days prior to Day 1; 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; Note: CRE is defined as Enterobacterales by susceptibility data of minimum inhibitory concentration (MIC) at least 2 micro g/mL to imipenem or meropenem OR imipenem or meropenem disk diffusion (zone diameter less than 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 methods and criteria in the institution (eg, phenotypic or molecular testing) 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.
Exclusion criteria
Exclusion criteria: 1. Has a history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious allergic reaction to carbapenems, cephems, penicillins, other beta-lactam antibiotics, or any beta-lactamase inhibitors (eg, tazobactam, sulbactam, or clavulanic acid); 2. Has known or suspected single or concurrent infection with Acinetobacter spp., metallo-beta-lactamase (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;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: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. Safety:The safety parameters include the incidence, severity, causality, and seriousness of TEAEs, and the evaluation of changes from baseline in safety laboratory test results, 12-lead ECGs, vital signs, and physical examinations. | — |
Countries
China, Croatia, Czech Republic, France, Georgia, Greece, Israel, Japan, Latvia, Slovakia, Spain, Taiwan, Thailand, Turkey
Contacts
Public ContactClinical Development Dept.
Meiji Seika Pharma Co.,Ltd.
Outcome results
None listed