Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)

Study Overview
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Brief Summary
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This is a Phase 3, randomized, double-blind, multicenter, non-inferiority study to evaluate the efficacy, safety, and tolerability of FEP-ZID vs. meropenem in the treatment of hospitalized adults with cUTI or AP. Approximately 528 hospitalized adult subjects (≥ 18 years of age) diagnosed with cUTI or AP will be enrolled in the study. The diagnosis of cUTI or AP will be based on a combination of clinical symptoms and signs plus the presence of pyuria. The total duration of treatment with study drug is 7 to 10 days. Each subject must remain hospitalized during the study drug treatment period; no outpatient parenteral antibiotic therapy is allowed.

Official Title
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A Phase 3, Randomized, Double-blind, Multicenter, Comparative Study to Determine the Efficacy and Safety of Cefepime-zidebactam vs. Meropenem in the Treatment of Complicated Urinary Tract Infection or Acute Pyelonephritis in Adults

Conditions
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Complicated Urinary Tract Infection, Acute Pyelonephritis

Intervention / Treatment
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* Drug: Cefepime-zidebactam (FEP-ZID)
* Drug: Meropenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age Provide a signed written informed consent prior to any study-specific procedures Meet the clinical criteria for either cUTI or AP Requires hospitalization to manage the cUTI or AP Agrees to use effective methods of contraception Exclusion Criteria: Known or suspected disease that may confound the assessment of efficacy. Receipt of more than 72 hours of prior antibiotic therapy except for those failing prior antibiotic therapy and/or having documented uropathogen resistant to the prior therapy. Rapidly progressive illness such that the subject is unlikely to survive the study period. Pregnant or breastfeeding women History of a seizure disorder requiring current treatment Creatinine clearance < 15 mL/min or on renal dialysis Neutropenia or elevated liver enzymes Hypersensitivity to beta-lactam antibiotics Unlikely to comply with the protocol or the Investigator considers that study participation may not be optimal for the subject

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cefepime-zidebactam (FEP-ZID)<br> | Drug: Cefepime-zidebactam (FEP-ZID)<br>* 3 g (2 g FEP + 1 g ZID) IV q8h<br>|
| Active Comparator: Meropenem<br> | Drug: Meropenem<br>* 1 g IV q8h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with overall success at Test-of-Cure | Overall success is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 colony forming units or CFU/mL) | Test Of Cure Visit (Day 17 ± 2 days) | 
| Percentage of subjects with Treatment-Emergent Adverse Events (TEAE) | Collection of number of adverse events. | Day 1 to the end of study Late Follow-Up visit (LFU) (26 ± 2 days)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with overall success at End-of-Treatment | Overall success is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (<1000 CFU/mL) | End of Treatment Visit (Day 7 - 10 ± 1 day) | 
| Percentage of subjects with clinical cure at End-of-Treatment | Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL)(CFU)/mL. | End of Treatment Visit (Day 7 - 10 ± 1 day) | 
| Percent of subjects with microbiological eradication at End-of-Treatment | Microbiologic eradication is defined as demonstrating <1000 CFU/mL of the bacterial pathogen found at study entry | End of Treatment Visit (Day 7 - 10 ± 1 day) | 
| Percentage of subjects with clinical cure at Test-of-Cure | Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL) | End of Treatment Visit (Day 17 ± 2 days) | 
| Percent of subjects with microbiological eradication at Test-of-Cure | Microbiologic eradication is defined as demonstrating <1000 CFU/mL of the bacterial | End of Treatment Visit (Day 17 ± 2 days) | 
| Percentage of subjects with clinical cure at Late Follow-up | Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to <1000 CFU/mL) | End of Treatment Visit (Day 26 ± 2 days) | 
| Plasma Concentration of FEP-ZID |  | On Days 1 and 3 of dosing prior to infusion, within 15 minutes after the end of infusion, and at 3 timepoints up to 7 hours hours post infusion |