Acute Pyelonephritis, Complicated Urinary Tract Infection
Conditions
Brief summary
This is a Phase 3, randomized, double-blind, multicenter, non-inferiority study to evaluate the efficacy, safety, and tolerability of FEP-ZID vs. meropenem in the treatment of hospitalized adults with cUTI or AP. Approximately 528 hospitalized adult subjects (≥ 18 years of age) diagnosed with cUTI or AP will be enrolled in the study. The diagnosis of cUTI or AP will be based on a combination of clinical symptoms and signs plus the presence of pyuria. The total duration of treatment with study drug is 7 to 10 days. Each subject must remain hospitalized during the study drug treatment period; no outpatient parenteral antibiotic therapy is allowed.
Interventions
DRUGMeropenem
1 g IV q8h
DRUGCefepime-zidebactam (FEP-ZID)
3 g (2 g FEP + 1 g ZID) IV q8h
Sponsors
Wockhardt
Medpace, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 18 years of age 2. Provide a signed written informed consent prior to any study-specific procedures 3. Meet the clinical criteria for either cUTI or AP 4. Requires hospitalization to manage the cUTI or AP 5. Agrees to use effective methods of contraception
Exclusion criteria
1. Known or suspected disease that may confound the assessment of efficacy. 2. Receipt of more than 72 hours of prior antibiotic therapy except for those failing prior antibiotic therapy and/or having documented uropathogen resistant to the prior therapy. 3. Rapidly progressive illness such that the subject is unlikely to survive the study period. 4. Pregnant or breastfeeding women 5. History of a seizure disorder requiring current treatment 6. Creatinine clearance \< 15 mL/min or on renal dialysis 7. Neutropenia or elevated liver enzymes 8. Hypersensitivity to beta-lactam antibiotics 9. Unlikely to comply with the protocol or the Investigator considers that study participation may not be optimal for the subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Overall Success at Test-of-Cure | Test Of Cure Visit (Day 17 ± 2 days) | Overall success is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to \<1000 colony forming units or CFU/mL) |
| Percentage of Subjects With Treatment-Emergent Adverse Events (TEAE) | Day 1 to the end of study Late Follow-Up visit (LFU) (26 ± 2 days)] | Collection of number of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Overall Success at End-of-Treatment | End of Treatment Visit (Day 7 - 10 ± 1 day) | Overall success is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (\<1000 CFU/mL) |
| Percentage of Subjects With Clinical Cure at End-of-Treatment | End of Treatment Visit (Day 7 - 10 ± 1 day) | Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to \<1000 CFU/mL)(CFU)/mL. |
| Percent of Subjects With Microbiological Eradication at End-of-Treatment | End of Treatment Visit (Day 7 - 10 ± 1 day) | Microbiologic eradication is defined as demonstrating \<1000 CFU/mL of the bacterial pathogen found at study entry |
| Percentage of Subjects With Clinical Cure at Test-of-Cure | Test-of-Cure (Day 17+-2) | Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to \<1000 CFU/mL) |
| Percent of Subjects With Microbiological Eradication at Test-of-Cure | Test-of-Cure (Day 17 ± 2 days) | Microbiologic eradication is defined as demonstrating \<1000 CFU/mL of the bacterial |
| Percentage of Subjects With Clinical Cure at Late Follow-up | Late Follow-up (Day 26 ± 2 days) | Clinical cure is defined as complete resolution of cUTI or AP symptoms present at study entry (or return to premorbid state) and no new cUTI or AP symptoms together with microbiologic eradication of the bacterial pathogen found at study entry (reduced to \<1000 CFU/mL) |
| Plasma Concentration of FEP-ZID | On Days 1 and 3 (+1) of dosing prior to infusion, within 15 minutes after the end of infusion, and at 3 timepoints up to 7 hours hours post infusion | Plasma samples from ZID-FEP-treated subjects were analyzed to determine concentrations of ZID and FEP using a validated assay. Pharmacokinetic analyses were based on the PK populations at pre-specified time points on Days 1 and 3 (+1). |
Countries
Bulgaria, China, Estonia, India, Lithuania, Mexico, Poland, Slovakia, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized >=18 years in MITT population | 529 Participants |
| Race/Ethnicity, Customized American Indianor Alaskan Native | 7 Participants |
| Race/Ethnicity, Customized Asian Chinese | 5 Participants |
| Race/Ethnicity, Customized Asian Non Chinese | 106 Participants |
| Race/Ethnicity, Customized White | 469 Participants |
| Region of Enrollment Bulgaria | 74 participants |
| Region of Enrollment China | 17 participants |
| Region of Enrollment Estonia | 41 participants |
| Region of Enrollment India | 36 participants |
| Region of Enrollment Lithuania | 93 participants |
| Region of Enrollment Mexico | 14 participants |
| Region of Enrollment Poland | 21 participants |
| Region of Enrollment Slovakia | 21 participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 234 Participants |
| Sex: Female, Male Male | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 352 | 0 / 177 |
| other Total, other adverse events | 35 / 352 | 19 / 177 |
| serious Total, serious adverse events | 8 / 352 | 1 / 177 |
Outcome results
None listed