Oral Sulopenem Versus Amoxicillin/Clavulanate for Uncomplicated Urinary Tract Infection in Adult Women

Study Overview
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Brief Summary
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IT001-310 is a clinical study which compares the effectiveness of oral sulopenem versus oral amoxicillin/clavulanate for the treatment of adult women with uncomplicated urinary tract infection.

Detailed Description
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IT001-310 is a Phase 3, randomized, multicenter, double-blind, double dummy, controlled study to compare oral sulopenem etzadroxil/probenecid (oral sulopenem) to oral amoxicillin/clavulanate for the treatment of adult female patients with uncomplicated urinary tract infection. Approximately 1966 adult women with uncomplicated urinary tract infection will be randomized in a 1:1 fashion to receive either oral sulopenem etzadroxil/probenecid or oral amoxicillin/clavulanate twice daily for 5 days. The primary outcome measure for efficacy evaluation will be the overall success (combined clinical and microbiologic success) on Day 12 (± 1 day)/Test of Cure (TOC).

Official Title
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A Prospective, Phase 3, Randomized, Multi-center, Double-blind Study of the Efficacy, Tolerability, and Safety of Oral Sulopenem Etzadroxil/Probenecid Versus Oral Amoxicillin/Clavulanate for Treatment of Uncomplicated Urinary Tract Infections (uUTI) in Adult Women

Conditions
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Urinary Tract Infections, Cystitis

Intervention / Treatment
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* Drug: Sulopenem etzadroxil/probenecid
* Drug: Amoxicillin/clavulanate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients ≥18 years of age with ≥24 hours and ≤96 hours of urinary symptoms attributable to a UTI Two of the following signs and symptoms of uUTI: urinary frequency, urinary urgency, pain or burning on micturition, suprapubic pain. A mid-stream urine specimen with evidence of pyuria as defined by either a machine-read dipstick positive for leukocyte esterase OR at least 10 white blood cells per cubic millimeter on microscopic analysis of unspun urine OR white blood cell count ≥10 cells/high-powered field (HPF) in the sediment of a spun urine Exclusion Criteria: Presence of signs and symptoms suggestive of acute pyelonephritis defined as: fever (temperature > 38° Celsius), chills, costovertebral angle tenderness, flank pain, nausea, and/or vomiting Receipt of antibacterial drug therapy potentially effective as treatment of uUTI within the prior 7 days Concurrent use of non-study treatments that would have a potential effect on outcome evaluations in patients with uUTI, including analgesics (e.g., non-steroidal anti-inflammatory drugs, aspirin, paracetamol etc.), phenazopyridine, and cranberry products. Any anatomical abnormality of the urinary tract, including surgically modified urinary tract anatomy, and obstructive uropathy due to nephrolithiasis, stricture, tumor, or fibrosis Ongoing urinary retention Neurogenic bladder Current resident of a long-term care facility Instrumentation of urinary tract in the previous 30 days An indwelling urinary catheter, ureteral stent or other foreign material in the urinary tract Any history of trauma to the pelvis or urinary tract Receiving hemodialysis, hemofiltration, peritoneal dialysis, or had a renal transplant History of allergy or hypersensitivity to carbapenems, β-lactams or probenecid, as formulated with their excipients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Sulopenem etzadroxil/probenecid<br>Sulopenem etzadroxil/probenecid 500 mg/500 mg PO twice daily for 5 days | Drug: Sulopenem etzadroxil/probenecid<br>* Oral sulopenem twice daily for 5 days<br>* Other names: Oral sulopenem;|
| Active Comparator: Amoxicillin/clavulanate<br>Amoxicillin/clavulanate PO twice daily for 5 days | Drug: Amoxicillin/clavulanate<br>* Oral Augmentin twice daily for 5 days<br>* Other names: Augmentin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants with Overall Success | Overall Success: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic success (eradication of the baseline pathogen) | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Overall Success | Overall Success: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic success (eradication of the baseline pathogen) | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Overall Success | Overall Success: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic success (eradication of the baseline pathogen) | Day 12+/-1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Modified Intent to Treat (MITT) Participants With Clinical Success | Clinical Success: Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Clinical Success | Clinical Success: Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Clinical Success | Clinical Success: Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Clinical Success | Clinical Success: Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Asymptomatic Bacteriuria | Asymptomatic Bacteriuria: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic Failure (persistence of the baseline pathogen) | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Asymptomatic Bacteriuria | Asymptomatic Bacteriuria: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic Failure (persistence of the baseline pathogen | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Asymptomatic Bacteriuria | Asymptomatic Bacteriuria: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic Failure (persistence of the baseline pathogen | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Microbiologic Success | Microbiologic Success: Eradication of the Baseline Pathogen | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Microbiologic Success | Microbiologic Success: Eradication of the Baseline Pathogen | Day 12+/-1 day | 
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Microbiologic Success | Microbiologic Success: Eradication of the Baseline Pathogen | Day 12+/-1 day |