Integral-1: Efficacy and Safety of Cefepime/Nacubactam or Aztreonam/Nacubactam Compared to Imipenem/Cilastatin in Subjects With Complicated Urinary Tract Infections or Acute Uncomplicated Pyelonephritis

Sponsor

Meiji Seika Pharma Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05887908

Collaborator

(none)

600

Enrollment

Location

Arms

14.3

Anticipated Duration (Months)

41.9

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Complicated Urinary Tract Infection Acute Pyelonephritis	Drug: co-administration of cefepime and nacubactam Drug: co-administration of aztreonam and nacubactam Drug: imipenem/cilastatin	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Multi-Center, Randomized, Double-Blind 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 or Acute Uncomplicated Pyelonephritis, in Adults

Actual Study Start Date :

May 23, 2023

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: co-administration of cefepime and nacubactam co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion)	Drug: co-administration of cefepime and nacubactam 2 g cefepime and 1 g nacubactam
Experimental: co-administration of aztreonam and nacubactam co-administration of 2 g aztreonam and 1 g nacubactam q8h (60 min. infusion)	Drug: co-administration of aztreonam and nacubactam 2 g aztreonama and 1 g nacubactam
Active Comparator: imipenem/cilastatin combination of 1 g imipenem/1 g cilastatin q8h (60 min. infusion)	Drug: imipenem/cilastatin 1 g imipenem/1 g cilastatin

Arm

Intervention/Treatment

Experimental: co-administration of cefepime and nacubactam

co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion)

Drug: co-administration of cefepime and nacubactam

2 g cefepime and 1 g nacubactam

Experimental: co-administration of aztreonam and nacubactam

co-administration of 2 g aztreonam and 1 g nacubactam q8h (60 min. infusion)

Drug: co-administration of aztreonam and nacubactam

2 g aztreonama and 1 g nacubactam

Active Comparator: imipenem/cilastatin

combination of 1 g imipenem/1 g cilastatin q8h (60 min. infusion)

Drug: imipenem/cilastatin

1 g imipenem/1 g cilastatin

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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;
Weight at most 140 kg;
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:

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.
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.
Has only a known Gram-positive primary uropathogen (at least 10^5 CFU/mL), isolated from study qualifying urine culture;