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This is a Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ertapenem-zidebactam Versus Ceftazidime-Avibactam in the Treatment of Hospitalized Adult Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis

20 settembre 2026 aggiornato da: Wockhardt

A Phase 2, Randomized, Open-Label, Multicentre, Comparative 3 Arm Study to Evaluate the Efficacy And Safety of Intravenous Ertapenem-zidebactam Versus Ceftazidime-Avibactam in the Treatment of Complicated Urinary Tract Infection or Acute Pyelonephritis in Adults

This is a Phase 2 randomized open label multicentre three arm comparative study evaluating the efficacy safety tolerability and pharmacokinetics of intravenous ertapenem zidebactam ERT ZID compared with ceftazidime avibactam CAZ AVI in adults with complicated urinary tract infection cUTI or acute pyelonephritis AP. Approximately 279 hospitalized participants aged 18 years and above will be enrolled from approximately 30 study sites in India and Europe and randomized in a 1 to 1 to 1 ratio to receive ERT ZID for 5 to 7 days ERT ZID for 7 to 10 days or CAZ AVI for 7 to 10 days. The primary endpoint is overall success at Test of Cure defined by clinical cure and microbiological eradication. Secondary assessments include clinical response microbiological response by pathogen outcomes pharmacokinetic parameters and plasma protein binding with safety monitored through adverse events laboratory tests vital signs and electrocardiograms.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Stimato)

279

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

  • Nome: Ranjeet Gutte Vice President, Global Clinical Development
  • Numero di telefono: 9819858489
  • Email: rgutte@wockhardt.com

Luoghi di studio

  • India
    • Andhra Pradesh
      • Visakhapatnam, Andhra Pradesh, India, 530002
    • Chhattisgarh
      • Raipur, Chhattisgarh, India, 492099
        • All India Institute of Medical Sciences, AIIMS, Raipur
        • Contatto:
    • Karnataka
      • Belagavi, Karnataka, India, 590010
        • KLES Dr. Prabhakar Kore Hospital and MRC
        • Contatto:
      • Mandya, Karnataka, India, 571401
        • Mandya Institute of Medical Sciences
        • Contatto:
      • Mysore, Karnataka, India, 570001
        • K R Hospital MMC and RI
        • Contatto:
    • Kerala
      • Kozhikode, Kerala, India, 673323
        • Malabar Medical College
        • Contatto:
    • Maharashtra
      • Nagpur, Maharashtra, India, 440024
        • Shravan Hospital Multispeciality and Kidney Institute Private Limited
        • Contatto:
      • Nashik, Maharashtra, India, 422002
        • Supe Heart and Diabetes Hospital and Research Centre
        • Contatto:
      • Pune, Maharashtra, India, 411039
      • Pune, Maharashtra, India, 412105
    • Rajasthan
      • Jaipur, Rajasthan, India, 302012
      • Jaipur, Rajasthan, India, 302017
      • Jaipur, Rajasthan, India, 302004
        • SMS Medical College and Hospital
        • Contatto:
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 600113
        • VHS Infectious Diseases Medical Centre
        • Contatto:
      • Coimbatore, Tamil Nadu, India, 641 018
        • KG Hospital and Post Graduate Medical Institute & Research Centre
        • Contatto:
      • Kanchipuram, Tamil Nadu, India, 603203
        • SRM Medical College Hospital and Research Centre
        • Contatto:
      • Madurai, Tamil Nadu, India, 625107
        • Meenakshi Mission Hospital and Research Centre
        • Contatto:
    • Telangana
      • Hyderabad, Telangana, India, 500003
        • Yashoda Hospital
        • Contatto:
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India, 226030
        • Medanta Hospital, Lucknow
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 90 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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 following clinical criteria for either cUTI or AP:

A. cUTI:

  1. 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

  2. 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 postvoid residual urine volume of ≥100 mL
    • Complete or partial obstructive uropathy (e.g., nephrolithiasis, tumour, 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 >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 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, AP will be considered the study entry diagnosis for randomization and analysis purposes. 4. 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 in urine sediment (spun urine) Note: The screening/baseline urine sample (within 48 hours prior to randomization) will be submitted for culture; however, trial participants may be randomized and administered study drug therapy prior to knowledge of screening/baseline urine culture results. 5. If known, the screening/baseline urine culture taken within 48 hours prior to randomization contains ≥105 colony forming units (CFU)/mL of a gram negative uropathogen likely to be susceptible to CAZ-AVI.

      6. Expectation, in the judgment of the investigator, that any implanted urinary instrumentation (e.g., nephrostomy tubes, ureteric stents) will be surgically removed or replaced before randomization or within 24 hours after randomization, unless removal or replacement is considered unsafe or contraindicated; note that temporary 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 sample for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated.

    Note: Urinary stone(s) (nephrolithiasis) present at Screening are also considered a removable source of infection.

    7. Requires hospitalization with administration of parenteral antibiotic therapy to manage the cUTI or AP in accordance with standard of care.

    8. All females (except those who have a documented surgical sterilization or are postmenopausal as defined below) must have a negative urine or serum pregnancy test (beta-human chorionic gonadotropin [β-HCG]) at Screening

    AND agree to the use of one of the following highly effective methods of contraception from Screening through TOC:

    • Surgical sterilization (defined as bilateral oophorectomy or bilateral salpingectomy, but excluding bilateral tubal occlusion)
    • Postmenopausal (defined by amenorrhea for at least 24 months following cessation of all exogenous hormonal treatments)
    • Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
    • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
    • Intrauterine device
    • Intrauterine hormone-releasing system
    • Sexual intercourse with only vasectomized partners, or
    • Abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the trial participant Note: A serum or urine pregnancy test will be performed at Screening for all female participants except those who are documented postmenopausal or surgically sterile.

    A negative result is required to confirm eligibility. All males must agree to use an acceptable barrier method of birth control (i.e., condom) with female partner(s) and must not donate sperm from Screening through TOC.

    Exclusion Criteria:

    1. 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 trial participant requiring haemodialysis
      • Where a urine culture result is available: - At least 1 uropathogen at ≥105 colony forming units per millilitre (CFU/mL) is resistant to CAZ-AVI, or - A gram-negative bacterial pathogen is not identified, or - The trial participant has a confirmed fungal cUTI with colony count ≥103 CFU/mL

    2. cUTI or AP that is known at Screening to be caused by a pathogen that is resistant to CAZ-AVI, including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis).

    3. Receipt of potentially effective systemic antibacterial therapy within 72 hours prior to randomization, with the exception of any of the following:

      • Receipt of a single dose of an allowed short-acting antibacterial agent within 72 hours prior to randomization (see Section25.1). For trial participants without documentation of failure on this prior therapy and/or documented uropathogen resistant to this prior therapy, this exception will be capped at a maximum of 10% of enrolment.
      • 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.

    4. Trial participants who may need ongoing antibacterial drug prophylaxis after treatment of cUTI (such as vesico-ureteral reflux etc).

    5. Confirmed or clinical suspicion of CAZ-AVI resistance.

    6. History of previous exposure to CAZ-AVI treatment (full course of treatment) in the last 90 days prior to randomization

    7. 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 trial participant is unlikely to survive the study period.

    8. Pregnant or breastfeeding women.

    9. Likely to require >10 days of antibiotic treatment to cure the current acute cUTI or AP, 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.

    10. 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).

    11. History of epilepsy or known seizure disorder requiring current treatment with anti-seizure medication, or confirmed or suspected encephalopathy (e.g., myoclonus, altered mental status, depressed level of consciousness).

    12. Trial participant requires concomitant treatment with valproic acid, divalproex, or probenecid.

    13. CrCl <30 mL/min or requirement for haemodialysis or CVVH

    14. Current or anticipated neutropenia defined as <500 neutrophils/mm3, or platelet count <50,000 per microliter.

    15. Screening serum total bilirubin ≥2 times the upper limit of normal (ULN) (unless elevated indirect bilirubin due to known Gilbert's syndrome), alanine aminotransferase ≥5 × ULN (or aspartate aminotransferase ≥5 × ULN if alanine aminotransferase activity not available), or alkaline phosphatase ≥2 × ULN.

    16. History of Clostridioides difficile-associated disease within 6 months prior to enrolment.

    17. History of serious or significant hypersensitivity or allergic reaction (e.g., anaphylaxis, urticaria, other significant reaction) to any β-lactam antibiotic.

    18. Prior receipt of ERT-ZID, prior randomization in this study, or use of any experimental drug or device within 30 days prior to enrolment.

    19. Unlikely to comply with the protocol (e.g., inability to return for all study visits), or any condition (including social circumstances) or clinically significant abnormality that, in the opinion of the investigator, is likely to interfere with optimal study participation (e.g., evaluation of study drug efficacy, determination of safety, or completion of the expected course of treatment).

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Ertapenem-zidebactam
Droga: Ertapenem-zidebactam

(2 g ERT + 2 g ZID) 4 g intravenously (IV) once daily (q24h) for 5 to 7 days
Comparatore attivo: Ceftazidime-Avibactam
Droga: Ceftazidime-Avibactam

(2 g ceftazidime + 0.5 g avibactam) 2.5 g IV every 8 hours (q8h) for 7 to 10 days
Sperimentale: Ertapenem Zidebactam
Droga: Ertapenam-Zidebactam

(2 g ERT + 2 g ZID) 4 g intravenously (IV) once daily (q24h) for 7 to 10 days

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Clinical Outcome at Test of Cure (TOC) - mMITT Analysis Set:
Lasso di tempo: Day 17 +3 days (TOC)

Clinical outcome assessed as Clinical Cure, Clinical Failure, or Clinical Indeterminate using the Daily Symptom Assessment questionnaire and Investigator assessment. Unit of measure: categorical (Clinical Cure/Clinical Failure/Clinical Indeterminate)
Day 17 +3 days (TOC)
Microbiological Outcome at Test of Cure (TOC) - mMITT Analysis Set
Lasso di tempo: Day 17 +3 days (TOC)

Microbiological outcome assessed as Microbiological Eradication, Microbiological Persistence, or Microbiological Indeterminate using urine culture with species-level identification and quantitative assessment of bacterial growth. Unit of measure: categorical (Microbiological Eradication/Microbiological Persistence/Microbiological Indeterminate).
Day 17 +3 days (TOC)
Safety and Tolerability
Lasso di tempo: Day 1 to Day 26 ± 2 days

Incidence of treatment-emergent adverse events (TEAEs), drug-related TEAEs, TEAEs leading to study drug discontinuation, and serious adverse events (SAEs), and incidence of potentially clinically significant changes in laboratory parameters, vital signs, and ECG parameters. Measurement tool: adverse-event reporting, clinical laboratory tests, vital signs, and electrocardiograms. Unit of measure: number and percentage of participants.
Day 1 to Day 26 ± 2 days

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Clinical Response at End of Treatment (EOT) - mMITT Analysis Set
Lasso di tempo: Day 5 to 10 days +24 hours (EOT)

Clinical response assessed as Clinical Response, Clinical Non-response, or Clinical Indeterminate using the Daily Symptom Assessment questionnaire and Investigator assessment. Unit of measure: categorical (Clinical Response/Clinical Non-response/Clinical Indeterminate).
Day 5 to 10 days +24 hours (EOT)
Microbiological Outcome at EOT - mMITT Analysis Set
Lasso di tempo: Day 5 to 10 days +24 hours (EOT)

Microbiological outcome assessed as Microbiological Eradication, Microbiological Persistence, or Microbiological Indeterminate using urine culture with species-level identification and quantitative assessment of bacterial growth. Unit of measure: categorical (Microbiological Eradication/Microbiological Persistence/Microbiological Indeterminate)
Day 5 to 10 days +24 hours (EOT)
By-Pathogen Overall Outcome at TOC
Lasso di tempo: Day 17 +3 days (TOC)

Overall outcome for each baseline uropathogen, based on the corresponding clinical and microbiological outcomes. Unit of measure: categorical (Overall Success/Overall Failure/Overall Indeterminate). Measurement tools: Daily Symptom Assessment questionnaire and Investigator assessment, and urine culture.
Day 17 +3 days (TOC)
By-Pathogen Microbiological Outcome at TOC
Lasso di tempo: Day 17 +3 days (TOC)

Microbiological outcome for each baseline uropathogen assessed using urine culture with species-level identification and quantitative assessment of bacterial growth. Unit of measure: categorical (Microbiological Eradication/Microbiological Persistence/Microbiological Indeterminate)
Day 17 +3 days (TOC)
By-Pathogen Clinical Outcome at TOC
Lasso di tempo: Day 17 +3 days (TOC)

Clinical outcome for each baseline uropathogen assessed using the Daily Symptom Assessment questionnaire and Investigator assessment. Unit of measure: categorical (Clinical Cure/Clinical Failure/Clinical Indeterminate)
Day 17 +3 days (TOC)
Maximum Plasma Concentration (Cmax) of ERT-ZID
Lasso di tempo: During the treatment period according to scheduled PK sampling on Day 1, Day 3 and Day 4.

Maximum plasma concentration of ertapenem-zidebactam measured from plasma PK samples. Unit of measure: concentration x time (15 min, between 1 to 2 hrs, between 5 to 7 hrs, between 9 to 11 hrs, between 20 to 23 hrs from the infusion of drug).
During the treatment period according to scheduled PK sampling on Day 1, Day 3 and Day 4.
AUC0-t of ERT-ZID
Lasso di tempo: During the treatment period according to scheduled PK sampling on Day 1, Day 3 and Day 4

Area under the plasma concentration-time curve of ertapenem-zidebactam from time 0 to the last quantifiable concentration. Unit of measure: concentration × time (15 min, between 1 to 2 hrs, between 5 to 7 hrs, between 9 to 11 hrs, between 20 to 23 hrs from the infusion of drug).
During the treatment period according to scheduled PK sampling on Day 1, Day 3 and Day 4
AUC0-inf of ERT-ZID
Lasso di tempo: During the treatment period according to scheduled PK sampling on Day 1, Day 3 and Day 4.

Area under the plasma concentration-time curve of ertapenem-zidebactam from time 0 to infinity. Unit of measure: concentration × time (15 min, between 1 to 2 hrs, between 5 to 7 hrs, between 9 to 11 hrs, between 20 to 23 hrs from the infusion of drug).
During the treatment period according to scheduled PK sampling on Day 1, Day 3 and Day 4.

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage (%) Plasma Protein Binding of ERT and ZID
Lasso di tempo: Day 1 to Day 26 ± 2 days

Percentage of plasma protein binding of ertapenem and zidebactam determined from blood samples collected from participants receiving ERT-ZID. Unit of measure: percentage (%). Measurement tool: plasma protein binding assessment from collected blood samples.
Day 1 to Day 26 ± 2 days

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Wockhardt

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

30 settembre 2026

Completamento primario (Stimato)

1 settembre 2027

Completamento dello studio (Stimato)

1 settembre 2027

Date di iscrizione allo studio

Primo inviato

6 settembre 2026

Primo inviato che soddisfa i criteri di controllo qualità

20 settembre 2026

Primo Inserito (Effettivo)

24 settembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

24 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

20 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • W-6777-202

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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