Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis

Phase 3

Completed

• Conditions: Complicated Urinary Tract Infection; Acute Pyelonephritis; cUTI; AP
• Interventions: Drug: co-administration of aztreonam and nacubactam; Drug: imipenem/cilastatin; Drug: co-administration of cefepime and nacubactam

• Registration Number: NCT05887908
• Lead Sponsor: Meiji Seika Pharma Co., Ltd.

Brief Summary

Phase 3 study to evaluate the efficacy and safety of cefepime/nacubactam or aztreonam/nacubactam compared to imipenem/cilastatin in the treatment of complicated urinary tract infections (cUTI) or acute uncomplicated pyelonephritis (AP).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-04-25
• Study Start: 2023-05-23
• Study First Submitted QC: 2023-05-24
• Study First Posted: 2023-06-05
• Primary Completion: 2024-11-22
• Study Completion: 2024-11-26
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-03
• Last Update Posted: 2025-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 614

Inclusion Criteria

1. Male or female patients at least18 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 most 140 kg;
3. Expectation, in the opinion of the Investigator, that the patient's cUTI or AP will require treatment with at least 5 days of IV antibiotics;

Exclusion Criteria

1. Has a known imipenem- and/or meropenem-resistant Gram-negative uropathogen (at least 10^5 CFU/mL), isolated from study-qualifying urine culture; Note: If after randomization the susceptibility testing indicates resistance to imipenem and/or meropenem, the patient may remain on the study drug at the Investigator's discretion.
2. Has known or suspected single or concurrent infection with Acinetobacter spp. or other organisms that are not adequately covered by the study drug (eg, concurrent viral, mycobacterial, or fungal infection) and needs to be managed with other anti-infectives; Note: Patients with qualifying pathogen coinfected 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 Investigator's discretion.
3. Has only a known Gram-positive primary uropathogen (at least 10^5 CFU/mL), isolated from study qualifying urine culture;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
co-administration of aztreonam and nacubactam	co-administration of aztreonam and nacubactam	co-administration of 2 g aztreonam and 1 g nacubactam q8h (60 min. infusion)
imipenem/cilastatin	imipenem/cilastatin	combination of 1 g imipenem/1 g cilastatin q8h (60 min. infusion)
co-administration of cefepime and nacubactam	co-administration of cefepime and nacubactam	co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion)

Primary Outcome Measures

Name	Time	Method
The primary efficacy endpoint is the proportion of patients who achieve composite clinical and microbiological success at TOC in the Microbiological Modified Intent-to-Treat (m-MITT) Population.	7 [±2] days after EOT [Day 10 to 23]	Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with a clinical outcome of cure at TOC in patients with secondary bacteremia at baseline	TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment	Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.; Assessment of clinical outcome was based on signs and symptoms, with cure defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia.
Proportion of patients with a microbiological outcome of eradication at TOC in patients with secondary bacteremia at baseline	TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment	Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.; Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.
Proportion of patients who achieve composite clinical and microbiological outcome	Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, FUP (Follow-Up visit): Day17 to Day30	Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication.; Assessment of clinical outcome was based on Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms of cUTI or AP that were present at screening, such that no further antimicrobial therapy is warranted.; Microbiological outcome was determined programmatically based on quantitative microbiological urine cultures, with eradication defined as the pathogen found at screening with 10\^5 CFU/ml or more reduced to less than 10\^3 CFU/ml.
Proportion of patients with a clinical outcome of cure	Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30	Assessment of clinical outcome was based on Investigator's evaluation of the patient's clinical signs and symptoms, with cure defined as the complete resolution (or return to premorbid state) of the baseline signs and symptoms of cUTI or AP that were present at screening, such that no further antimicrobial therapy is warranted.
Proportion of patients with a microbiological outcome of eradication	Outcome measurements were assessed at various visits: EA (Earlly Assessment): Day4, EOT (End of Treatment): Day5 to Day14, TOC (Test of Cure visit): Day10 to Day 23, FUP (Follow-Up visit): Day17 to Day30	Microbiological outcome was determined programmatically based on quantitative microbiological urine cultures, with eradication defined as the pathogen found at screening with 10\^5 CFU/ml or more reduced to less than 10\^3 CFU/ml.
Proportion of patients who are free from the definition of secondary bacteremia AND a clinical outcome of cure AND a microbiological outcome of eradication from cUTI or AP at TOC in patients with secondary bacteremia at baseline	TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment	Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.; For cUTI/AP,Assessment is done by the same way as "Proportion of patients who achieve composite clinical and microbiological outcome".; For secondary bacteremia, assessment of clinical outcome was based on signs and symptoms, with cure defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia.; Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.
Proportion of patients who are free from secondary bacteremia in patients with secondary bacteremia at TOC	TOC (Test of Cure visit): Day 10 to Day 23 after the start of treatment	Patients with isolation of a gram-negative bacteria from at least 1 blood culture at baseline and this isolated pathogen is also identified from the site of infection and signs and symptoms of secondary bacteremia were determined programmatically as secondary bacteremia.; Assessment of clinical outcome was based on signs and symptoms, with cure defined as complete resolution or significant improvement of the baseline signs and symptoms of secondary bacteremia.; Microbiological outcome will be determined programmatically based on blood cultures, with eradication defined as the pathogen found at screening is negative in blood culture.

Trial Locations

Locations (1)

Meiji Research Site; 🇪🇪 Meegomäe, Võrumaa, Estonia