Evaluation of Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections

Study Overview
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Brief Summary
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This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with complicated urinary tract infections (cUTIs) who are otherwise relatively healthy.

Detailed Description
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This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs who are otherwise relatively healthy. Patients with Acute Pyelonephritis may also be enrolled. Approximately 80 patients will be randomized to receive either 1 g ETX2514/1 g sulbactam IV or matching placebo every 6 hours (q6h). All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.

Official Title
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A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous Sulbactam-ETX2514 in the Treatment of Hospitalized Adults With Complicated Urinary Tract Infections, Including Acute Pyelonephritis

Conditions
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Complicated Urinary Tract Infection, Acute Pyelonephritis

Intervention / Treatment
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* Drug: Sulbactam-ETX2514
* Drug: Placebo
* Drug: Imipenem-cilastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient as permitted by local law and institutional Standard Operating Procedures. Male or female, 18 to 90 years of age, inclusive. Expectation, in the judgment of the Investigator, that the patient's cUTI would require initial hospitalization and treatment with IV antibiotics. Documented or suspected cUTI or Acute pyelonephritis (AP). Exclusion Criteria: Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter. Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization that would interfere with evaluation of response to the study antibiotics. Patient requires continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study. Receipt of a single dose of a long-acting, potentially-effective systemic antibiotic with activity against Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to randomization. Requirement at time of randomization for any reason for additional systemic antimicrobial therapy (including antibacterial, antimycobacterial, or antifungal therapy) other than study drug, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study [from randomization through the Late Follow-up (LFU) Visit]. Any patients previously randomized in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Interventional Model Description: This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin<br> | Drug: Sulbactam-ETX2514<br>* The ETX2514SUL regimen of 1 g ETX2514/1 g sulbactam infused over 3 hours q6h.<br>* Other names: ETX2514SUL;Drug: Imipenem-cilastatin<br>* All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.<br>|
| Placebo Comparator: Placebo + Imipenem/Cilastatin<br> | Drug: Placebo<br>* Matching 1g IV solution.<br>Drug: Imipenem-cilastatin<br>* All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Success | The primary efficacy endpoint for this study was the proportion of patients with an overall success (clinical cure and micro-biologic eradication) for the m-MITT (Micro-biologically Modified Intent-to-Treat) Population at the TOC Visit. | From baseline through day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure | Proportion of patients with a response of clinical cure for the MITT(modified intent to treat), m-MITT (microbiologically modified intent to treat), CE(clinically evaluable), and ME(microbiologically evaluable) populations at the TOC(test of cure) visit. | Baseline to day 21 | 
| Microbiologic Eradication | Proportion of patients with a response of microbiologic eradication for the m-MITT(microbiologically modified intent to treat) and ME(microbiologically evaluable) populations at the TOC visit | Baseline to day 21 |