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

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

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

Study Overview

• Status: Completed
• Conditions: Uncomplicated Urinary Tract Infections
• Intervention / Treatment: Drug: Sulopenem-Etzadroxil/Probenecid; Drug: Ciprofloxacin

• Study Type: Interventional
• Enrollment (Actual): 1671
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Medical Facility
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Medical Facility
    • Tolleson, Arizona, United States, 85353
      • Medical Facility
  • California
    • Cerritos, California, United States, 90703
      • Medical Facility
    • Chula Vista, California, United States, 91911
      • Medical Facility
    • Fullerton, California, United States, 92835
      • Medical Facility
    • La Mesa, California, United States, 91942
      • Medical Facility
    • Los Angeles, California, United States, 90057
      • Medical Facility
    • San Diego, California, United States, 92108
      • Medical Facility
    • Sylmar, California, United States, 91342
      • Medical Facility
  • District of Columbia
    • Washington, District of Columbia, United States, 20011
      • Medical Facility
  • Florida
    • Bradenton, Florida, United States, 34209
      • Medical Facility
    • Clearwater, Florida, United States, 33761
      • Medical Facility
    • Doral, Florida, United States, 33166
      • Medical Facility
    • Edgewater, Florida, United States, 32132
      • Medical Facility
    • Hialeah, Florida, United States, 33012
      • Medical Facility
    • Lauderdale Lakes, Florida, United States, 33319
      • Medical Facility
    • Miami, Florida, United States, 33144
      • Medical Facility
    • Miami, Florida, United States, 33126
      • Medical Facility
    • Miami, Florida, United States, 33135
      • Medical Facility
    • Miami, Florida, United States, 33145
      • Medical Facility
    • Miami, Florida, United States, 33155
      • Medical Facility
    • Miami, Florida, United States, 33165
      • Medical Facility
    • Miami, Florida, United States, 33172
      • Medical Facility
    • Miami, Florida, United States, 33173
      • Medical Facility
    • Miami Springs, Florida, United States, 33166
      • Medical Facility
    • New Port Richey, Florida, United States, 34653
      • Medical Facility
    • Ormond Beach, Florida, United States, 32174
      • Medical Facility
    • Palmetto Bay, Florida, United States, 33157
      • Medical Facility
    • Saint Petersburg, Florida, United States, 33711
      • Medical Facility
    • Winter Haven, Florida, United States, 33880
      • Medical Facility
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Medical Facility
    • Norcross, Georgia, United States, 30092
      • Medical Facility
    • Perry, Georgia, United States, 31069
      • Medical Facility
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Medical Facility
    • Metairie, Louisiana, United States, 70115
      • Medical Facility
    • New Orleans, Louisiana, United States, 70115
      • Medical Facility
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Medical Facility
    • Las Vegas, Nevada, United States, 89121
      • Medical Facility
  • New York
    • Brooklyn, New York, United States, 11215
      • Medical Facility
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Medical Facility
  • Oklahoma
    • Hugo, Oklahoma, United States, 74743
      • Medical Facility
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • Medical Facility
    • Lancaster, South Carolina, United States, 29720
      • Medical Facility
    • Myrtle Beach, South Carolina, United States, 29572
      • Medical Facility
  • Texas
    • Austin, Texas, United States, 78705
      • Medical Facility
    • Austin, Texas, United States, 78735
      • Medical Facility
    • Carrollton, Texas, United States, 75010
      • Medical Facility
    • Corpus Christi, Texas, United States, 78414
      • Medical Facility
    • Dallas, Texas, United States, 75204
      • Medical Facility
    • Houston, Texas, United States, 77029
      • Medical Facility
    • Houston, Texas, United States, 77036
      • Medical Facility
    • Pearland, Texas, United States, 77584
      • Medical Facility
    • Plano, Texas, United States, 75024
      • Medical Facility
    • Sugar Land, Texas, United States, 77478
      • Medical Facility
  • Utah
    • Bountiful, Utah, United States, 84010
      • Medical Facility
    • Saint George, Utah, United States, 84790
      • Medical Facility
    • Salt Lake City, Utah, United States, 84109
      • Medical Facility
    • Salt Lake City, Utah, United States, 84121
      • Medical Facility
    • South Jordan, Utah, United States, 84095
      • Medical Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female patients ≥18 years of age with 24-96 hours of urinary symptoms attributable to a urinary tract infection (UTI)
2. Two of the following signs and symptoms of uUTI: urinary frequency, urinary urgency, pain or burning micturition, suprapubic pain

3. A mid-stream urine specimen with:

   1. a dipstick analysis positive for nitrite AND
   2. 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

4. Has given written informed consent to participate in the study.

Exclusion Criteria:

1. Presence of signs and symptoms suggestive of acute pyelonephritis: fever (temperature > 38°Celsius), chills, costovertebral angle tenderness, flank pain, nausea, and/or vomiting
2. Receipt of antibacterial drug therapy potentially effective as treatment of uUTI within the prior 7 days
3. Concurrent use of non-study treatments that would have a potential effect on outcome evaluations in patients with uUTI
4. Patients with ileal loops or urinary stoma
5. Patients with an indwelling urinary catheter in the previous 30 days
6. Patients with paraplegia
7. Patients who are likely to receive ongoing antibacterial drug prophylaxis after treatment of uUTI (e.g., patients with vesico-ureteral reflux)
8. Any history of trauma to the pelvis or urinary tract
9. 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
10. Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
11. Known history of creatinine clearance <50 mL/min
12. Patients known to have liver disease
13. Patients who are pregnant, or females of child-bearing age unable to take adequate contraceptive precautions
14. Patients with uncontrolled diabetes mellitus
15. Patients with history of blood dyscrasias
16. Patients with history of uric acid kidney stones
17. Patients with acute gouty attack
18. Patients on chronic methotrexate therapy
19. Patient known to be immunocompromised
20. Patients with a known history of myasthenia gravis
21. Patients who require concomitant administration of tizanidine or valproic acid
22. Patients with a history of allergy or hypersensitivity to carbapenems, beta-lactams, quinolones or probenecid
23. 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
24. History of seizures
25. Use of any other investigational drug in the 30 days prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sulopenem-etzadroxil/probenecid; Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days	Drug: Sulopenem-Etzadroxil/Probenecid; Treatment of uncomplicated urinary tract infection
Active Comparator: Ciprofloxacin; Ciprofloxacin 250 mg PO administered twice daily for 3 days	Drug: Ciprofloxacin; Treatment of uncomplicated urinary tract infection; Other Names: Cipro

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) 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)	12 +/- 1 day

Collaborators and Investigators

• Sponsor: Iterum Therapeutics, International Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): January 16, 2020
• Study Completion (Actual): January 20, 2020

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 25, 2017
• First Posted (Actual): November 28, 2017

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Gout Suppressants; Cytochrome P-450 CYP1A2 Inhibitors; Renal Agents; Uricosuric Agents; Ciprofloxacin; Probenecid
• Other Study ID Numbers: IT001-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No