Oral Sulopenem-etzadroxil/Probenecid Versus Ciprofloxacin for Uncomplicated Urinary Tract Infection in Adult Women

Study Overview
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Brief Summary
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This is a prospective, Phase 3, randomized, multi-center, double-blind study of the efficacy, tolerability, and safety of oral sulopenem-etzadroxil/probenecid versus oral ciprofloxacin for treatment of uncomplicated urinary tract infection (uUTI) in adult women

Official Title
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A Prospective Phase 3 Randomized Multi-center Double-blind Study of Efficacy Tolerability & Safety of Oral Sulopenem-etzadroxil/Probenecid vs Ciprofloxacin for Treatment of Uncomplicated Urinary Tract Infections (uUTI) in Adult Women

Conditions
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Uncomplicated Urinary Tract Infections

Intervention / Treatment
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* Drug: Sulopenem-Etzadroxil/Probenecid
* Drug: Ciprofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients ≥18 years of age with 24-96 hours of urinary symptoms attributable to a urinary tract infection (UTI) Two of the following signs and symptoms of uUTI: urinary frequency, urinary urgency, pain or burning micturition, suprapubic pain A mid-stream urine specimen with: a dipstick analysis positive for nitrite AND evidence of pyuria as defined by either: i. a dipstick analysis positive for leukocyte esterase ii. at least 10 white blood cells per cubic millimeter on microscopic analysis of unspun urine iii. White blood cell count ≥10 cells/high-powered field in the sediment of a spun urine Has given written informed consent to participate in the study. Exclusion Criteria: Presence of signs and symptoms suggestive of acute pyelonephritis: 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 Patients with ileal loops or urinary stoma Patients with an indwelling urinary catheter in the previous 30 days Patients with paraplegia Patients who are likely to receive ongoing antibacterial drug prophylaxis after treatment of uUTI (e.g., patients with vesico-ureteral reflux) Any history of trauma to the pelvis or urinary tract Patient's urine culture, if available at study entry, identify more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant Known history of creatinine clearance <50 mL/min Patients known to have liver disease Patients who are pregnant, or females of child-bearing age unable to take adequate contraceptive precautions Patients with uncontrolled diabetes mellitus Patients with history of blood dyscrasias Patients with history of uric acid kidney stones Patients with acute gouty attack Patients on chronic methotrexate therapy Patient known to be immunocompromised Patients with a known history of myasthenia gravis Patients who require concomitant administration of tizanidine or valproic acid Patients with a history of allergy or hypersensitivity to carbapenems, beta-lactams, quinolones or probenecid Patient is considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality History of seizures Use of any other investigational drug in the 30 days prior to the study

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 PO twice daily for 5 days | Drug: Sulopenem-Etzadroxil/Probenecid<br>* Treatment of uncomplicated urinary tract infection<br>|
| Active Comparator: Ciprofloxacin<br>Ciprofloxacin 250 mg PO administered twice daily for 3 days | Drug: Ciprofloxacin<br>* Treatment of uncomplicated urinary tract infection<br>* Other names: Cipro;|

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 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 | 
| Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Overall Success | Overall Success is Clinical Success (resolution of uUTI symptoms present at study entry and no new uUTI symptoms) AND Microbiologic success (eradication of the baseline pathogen) | Day 12 +/- 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Patients With Microbiologic Success | Microbiologic success is defined as eradication of the baseline pathogen (<1000 Colony Forming Units (CFU)/mL) at the Test of Cure visit | Day 12+/-1 day |