Urinary Tract Infections, Cystitis
Conditions
Brief summary
Study 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
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).
Interventions
Oral sulopenem twice daily for 5 days
Oral Augmentin twice daily for 5 days
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Success | Day 12+/-1 day | 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) |
| Overall Success Susceptible Population | Day 12+/-1 day | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Success Susceptible Population | Day 12+/-1 day | Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms |
| Clinical Success Modified Intent-to-treat Population | Day 12+/-1 day | Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms |
| Microbiologic Success Susceptible Population | Day 12+/-1 day | Microbiologic Success: Eradication of the Baseline Pathogen |
| Microbiologic Success | Day 12+/-1 day | Eradication of the Baseline Pathogen |
| Clinical Success | Day 12+/-1 day | Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulopenem Etzadroxil/Probenecid Sulopenem etzadroxil/probenecid 500 mg/500 mg PO twice daily for 5 days
Sulopenem etzadroxil/probenecid: Oral sulopenem twice daily for 5 days | 522 |
| Amoxicillin/Clavulanate Amoxicillin/clavulanate 875 mg/125 mg PO twice daily for 5 days
Amoxicillin/clavulanate: Oral Augmentin twice daily for 5 days | 468 |
| Total | 990 |
Baseline characteristics
| Characteristic | Sulopenem Etzadroxil/Probenecid | Amoxicillin/Clavulanate | Total |
|---|---|---|---|
| Age, Continuous | 50.3 years STANDARD_DEVIATION 17.31 | 48.6 years STANDARD_DEVIATION 17.18 | 49.5 years STANDARD_DEVIATION 17.26 |
| Diabetes | 86 Participants | 68 Participants | 154 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 333 Participants | 296 Participants | 629 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants | 171 Participants | 360 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 8 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 84 Participants | 84 Participants | 168 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) White | 419 Participants | 370 Participants | 789 Participants |
| Region of Enrollment United States | 522 participants | 468 participants | 990 participants |
| Sex: Female, Male Female | 522 Participants | 468 Participants | 990 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 | 0 / 1,107 | 0 / 1,107 |
| other Total, other adverse events | 198 / 1,107 | 118 / 1,107 |
| serious Total, serious adverse events | 0 / 1,107 | 5 / 1,107 |
Outcome results
Primary
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: Microbiologic Modified Intent to Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Overall Success | 318 Participants |
| Amoxicillin/Clavulanate | Overall Success | 260 Participants |
Primary
Overall Success Susceptible Population
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: Microbiological Modified intent-to-treat Susceptible Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Overall Success Susceptible Population | 296 Participants |
| Amoxicillin/Clavulanate | Overall Success Susceptible Population | 243 Participants |
Secondary
Clinical Success
Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms
Time frame: Day 12+/-1 day
Population: Microbiological Modified Intent-to-treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Clinical Success | 397 Participants |
| Amoxicillin/Clavulanate | Clinical Success | 358 Participants |
Secondary
Clinical Success Modified Intent-to-treat Population
Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms
Time frame: Day 12+/-1 day
Population: Modified Intent-to-treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Clinical Success Modified Intent-to-treat Population | 851 Participants |
| Amoxicillin/Clavulanate | Clinical Success Modified Intent-to-treat Population | 849 Participants |
Secondary
Clinical Success Susceptible Population
Resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms
Time frame: Day 12+/-1 day
Population: Microbiological Modified Intent-to-treat Susceptible Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Clinical Success Susceptible Population | 371 Participants |
| Amoxicillin/Clavulanate | Clinical Success Susceptible Population | 339 Participants |
Secondary
Microbiologic Success
Eradication of the Baseline Pathogen
Time frame: Day 12+/-1 day
Population: Microbiological Modified Intent-to-treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Microbiologic Success | 390 Participants |
| Amoxicillin/Clavulanate | Microbiologic Success | 315 Participants |
Secondary
Microbiologic Success Susceptible Population
Microbiologic Success: Eradication of the Baseline Pathogen
Time frame: Day 12+/-1 day
Population: Microbiological Modified Intent-to-treat Susceptible Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulopenem Etzadroxil/Probenecid | Microbiologic Success Susceptible Population | 361 Participants |
| Amoxicillin/Clavulanate | Microbiologic Success Susceptible Population | 295 Participants |