Phase 3 Study of Cefepime-zidebactam (FEP-ZID) in Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)

Phase 3

• Conditions: 10 Acute tubulo-interstitial nephritis; N390 Urinary tract infection, site not specified; Acute tubulo-interstitial nephritis; Urinary tract infection, site not specified; N390

• Registration Number: PER-021-22
• Lead Sponsor: Wockhardt Bio AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-21
• Study Completion: 2023-06-28
• Last Update Posted: 20 August 2024

Recruitment & Eligibility

• Status: Without startig enrollment
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

Male or female = 18 years of age

Provide a signed written informed consent prior to any study-specific procedures

Meet the following clinical criteria for either cUTI or AP:
A.cUTI:
a.Have at least TWO of the following new-onset or worsening symptoms or signs:
•Fever (oral, tympanic, or rectal temperature > 38°C [> 100.4°F]), which must be observed and documented by a health care provider
•Nausea or vomiting
• Dysuria, increased urinary frequency, or urinary urgency
•Lower abdominal, suprapubic, or pelvic pain
b. Have at least ONE of the following complicating factors:
•Use of intermittent urethral catheterization or presence of an indwelling urethral catheter (Note: indwelling urethral catheters that have been in place for > 24 hours prior to Screening must be removed or replaced prior to collection of the screening urine for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated)
•Current known functional or anatomical abnormality of the urogenital tract, including anatomic malformations or neurogenic bladder, or with a post-void residual urine volume of = 100 mL
•Complete or partial obstructive uropathy (e.g., nephrolithiasis, tumor, fibrosis, urethral stricture) that is expected to be medically or surgically treated during study drug therapy (prior to EOT)
•Azotemia, defined as blood urea nitrogen (BUN) > 20 mg/dL (or blood urea > 42.8 mg/dL) or serum creatinine > 1.4 mg/dL, due to known prior intrinsic renal disease
•Documented history of urinary retention in men (e.g., previously diagnosed benign prostatic hypertrophy)
B.AP, defined as acute flank pain (onset within 7 days prior to randomization) or costovertebral angle (CVA) tenderness on physical examination, plus at least ONE of the following new-onset or worsening symptoms or signs:
•Fever (oral, tympanic, or rectal temperature > 38°C [> 100.4°F]), which must be observed and documented by a health care provider
•Nausea or vomiting
•Dysuria, increased urinary frequency, or urinary urgency
Note: If criteria for both cUTI and AP are met, cUTI will be considered the study entry diagnosis for randomization and analysis purposes.

Evidence of pyuria within 48 hours prior to randomization, as determined by an adequate midstream clean-catch urine specimen or other appropriate method that minimizes the risk of bacterial contamination with ONE of the following findings:
•Positive leukocyte esterase on urinalysis, (where positive result is at least ++ or moderate as indicated on a urine dipstick)
•White blood cell (WBC) count = 10 cells/mm3 in unspun urine
•WBC count = 10 cells/high-power field (HPF) in urine sediment (spun urine)
Note: The screening/baseline urine sample (within 48 hours prior to randomization) will be submitted for culture; however, subjects may be randomized and administered study drug therapy prior to knowledge of screening/baseline urine culture results.

Expectation, in the judgment of the Investigator, that any implanted urinary instrumentation (e.g., nephrostomy tu

Exclusion Criteria

Pregnant or breastfeeding women

Known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy, including but not limited to the following:
•Perinephric or renal abscess
•Uncomplicated lower UTI (e.g., cystitis)
•Recent trauma to the pelvis or urinary tract
•Polycystic kidney disease
•Chronic vesicoureteral reflux
•Previous or planned cystectomy or permanent urinary diversion (e.g., ileal loop, cutaneous ureterostomy)
•Acute or chronic bacterial prostatitis, orchitis, or epididymitis
•Concurrent non-renal source of infection (e.g., endocarditis, osteomyelitis, abscess, meningitis, pneumonia)
•Previous or planned renal transplant or subject requiring hemodialysis
•cUTI or AP that is known at Screening to be caused by a pathogen that is resistant to meropenem, including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis)

Likely to require > 10 days of antibiotic treatment to cure the current acute cUTI, or likely to receive any additional systemic antimicrobial therapy during the study period (including antibacterial, antimycobacterial, or antifungal therapy or prophylaxis) other than study drug, with the exception of (1) a single oral dose of any antifungal treatment for vaginal candidiasis, or (2) a glycopeptide (e.g., vancomycin), oxazolidinone (e.g., linezolid), or daptomycin given for a Gram-positive infection.

Receipt of potentially-effective systemic antibacterial therapy within 48 hours prior to randomization, with the exception of any of the following:
•Receipt of a single dose of a short-acting antibacterial agent (Appendix I) (no more than 15% of of subjects will be enrolled with this exception).
•Receipt of > 48 hours of prior antibiotic therapy and in the Investigator's opinion, failed that prior antibiotic therapy (i.e., worsening signs and symptoms).
•Documented to have cUTI or AP caused by a pathogen that is not susceptible to the prior antibiotic therapy.

Rapidly progressive or terminal illness with a high risk of mortality due to any cause, including but not limited to acute hepatic failure, respiratory failure, or septic shock, such that the subject is unlikely to survive the study period.

Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy).

History of epilepsy or known seizure disorder requiring current treatment with antiseizure medication.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The Overall outcome will be divided into:<br>•Overall success: Criteria met for clinical cure at TOC and overall microbiological eradication at the corresponding visit.<br>•Overall failure: Criteria met for clinical failure at TOC or overall microbiological persistence.<br>•Overall indeterminate: Study data are missing for evaluation of clinical or microbiological outcome for any reason and the subject cannot otherwise be declared an overall failure at the given visit.<br> NAME OF THE RESULT: Overall outcome (composite of clinical outcome and microbiological outcome) at<br>TOC (mMITT population)<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: Day 17 ± 2 days