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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Complicated Urinary Tract Infection, Acute Pyelonephritis

Intervention / Treatment
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* Drug: co-administration of cefepime and nacubactam
* Drug: co-administration of aztreonam and nacubactam
* Drug: imipenem/cilastatin


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Composite clinical and microbiological success is defined as the composite clinical outcome of cure and the microbiological outcome of eradication. | 7 [±2] days after EOT [Day 10 to 23] |