Uncomplicated Urinary Tract Infections
Conditions
Brief summary
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
Interventions
Treatment of uncomplicated urinary tract infection
DRUGCiprofloxacin
Treatment of uncomplicated urinary tract infection
Sponsors
Iterum Therapeutics, International Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Overall Success | Day 12+/-1 day | 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) |
| Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Overall Success | Day 12 +/- 1 day | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Patients With Microbiologic Success | Day 12+/-1 day | Microbiologic success is defined as eradication of the baseline pathogen (\<1000 Colony Forming Units (CFU)/mL) at the Test of Cure visit |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Overall Success | 12 +/- 1 day | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulopenem-etzadroxil/Probenecid Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days
Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection | 787 |
| Ciprofloxacin Ciprofloxacin 250 mg PO administered twice daily for 3 days
Ciprofloxacin: Treatment of uncomplicated urinary tract infection | 803 |
| Total | 1,590 |
Baseline characteristics
| Characteristic | Sulopenem-etzadroxil/Probenecid | Ciprofloxacin | Total |
|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 18.8 | 50.0 years STANDARD_DEVIATION 19.1 | 49.9 years STANDARD_DEVIATION 19 |
| Diabetes | 93 Participants | 106 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 253 Participants | 232 Participants | 485 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 529 Participants | 570 Participants | 1099 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Russia | 195 participants | 225 participants | 420 participants |
| Region of Enrollment Ukraine | 144 participants | 137 participants | 281 participants |
| Region of Enrollment United States | 448 participants | 441 participants | 889 participants |
| Sex: Female, Male Female | 787 Participants | 803 Participants | 1590 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 833 | 0 / 827 |
| other Total, other adverse events | 103 / 833 | 21 / 827 |
| serious Total, serious adverse events | 6 / 833 | 2 / 827 |
Outcome results
Primary
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)
Time frame: Day 12+/-1 day
Population: micro-MITTR population: patients with baseline uropathogen non-susceptible to the comparator ciprofloxacin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulopenem-etzadroxil/Probenecid | Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Overall Success | 62.6 percentage of participants |
| Ciprofloxacin | Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Overall Success | 36.0 percentage of participants |
Primary
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)
Time frame: Day 12 +/- 1 day
Population: micro-MITTS population: patients with baseline uropathogen susceptible to the comparator ciprofloxacin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulopenem-etzadroxil/Probenecid | Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Overall Success | 66.8 percentage of participants |
| Ciprofloxacin | Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Overall Success | 78.6 percentage of participants |
Secondary
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
Time frame: Day 12+/-1 day
Population: micro-MITTR population: patients with baseline uropathogen non-susceptible to the comparator ciprofloxacin.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulopenem-etzadroxil/Probenecid | Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Patients With Microbiologic Success | 74.1 percentage of participants |
| Ciprofloxacin | Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Patients With Microbiologic Success | 49.6 percentage of participants |
Other Pre-specified
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)
Time frame: 12 +/- 1 day
Population: micro-MITT population: micro-MITTR and micro-MITTS (ciprofloxacin nonsusceptible and ciprofloxacin susceptible) populations combined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulopenem-etzadroxil/Probenecid | Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Overall Success | 65.6 percentage of participants |
| Ciprofloxacin | Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Overall Success | 67.9 percentage of participants |