Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02753946
• Date of registration: 13/04/2016
• Prospective Registration: No
• Primary sponsor: Nabriva Therapeutics AG
• Public title: Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections ZEUS
• Scientific title: Randomized, Double-Blind, Comparative Study to Evaluate the Safety and Efficacy of ZTI-01 vs Piperacillin/Tazobactam in the Treatment of cUTI/AP Infection in Hospitalized Adults
• Date of first enrolment: April 2016
• Target sample size: 465
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02753946
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2/Phase 3

Countries of recruitment

Belarus, Bulgaria, Croatia, Czech Republic, Czechia, Estonia, Georgia, Greece, Hungary, Latvia, Lithuania, Poland, Romania, Russian Federation, Slovakia, Ukraine, United States

Contacts

• Name: Evelyn J Ellis-Grosse, PhD
• Affiliation: Zavante Therapeutics, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. A signed informed consent form (ICF);

2. Male or female, at least 18 years of age;

3. Diagnosis requires hospitalization and treatment with intravenous (IV) antibiotics;

4. Documented or suspected cUTI or AP including at least 2 protocol defined signs and
symptoms and a urine specimen with evidence of pyuria plus at least one protocol
defined associated risk

5. Pretreatment baseline urine culture specimen

6. Expectation that any implanted urinary instrumentation will be removed or replaced not
longer than 24 hours, after randomization;

7. Expectation that patient will survive anticipated duration of the study;

8. Patient requires initial hospitalization to manage the cUTI or AP;

9. Women of childbearing potential have had a negative pregnancy test before
randomization and be willing to consistently use a highly effective method of
contraception

10. Male study participants will be required to use condoms with a spermicide throughout
study

Exclusion Criteria:

1. Presence of any of the following conditions: perinephric abscess, renal
corticomedullary abscess, uncomplicated urinary tract infection, recent history of
trauma to the pelvis or urinary tract, polycystic kidney disease, chronic
vesicoureteral reflux, previous or planned renal transplantation; patients receiving
dialysis/hemodialysis/CVVH, previous or planned cystectomy or ileal loop surgery;
known or suspected infection; caused by pathogen resistant to study treatment
antibiotics

2. Presence of suspected or confirmed acute bacterial prostatitis, orchitis,
epididymitis, or chronic bacterial prostatitis as determined by history and/or
physical examination;

3. Gross hematuria requiring intervention;

4. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery
planned during the study period;

5. Creatinine clearance <20 mL/min using the Cockcroft-Gault formula;

6. Non-renal source of infection such as endocarditis, osteomyelitis, abscess,
meningitis, or pneumonia diagnosed within 7 days prior to randomization;

7. Signs of severe sepsis as defined per protocol;

8. Pregnant or breastfeeding women;

9. Known seizure disorder requiring current treatment with anti-seizure medication which
would prohibit the patient from complying with the protocol;

10. Cancer chemotherapy, immunosuppressive medications for transplantation, or medications
for rejection of transplantation with 30 days of randomization;

11. Significant hepatic disease or dysfunction, including known acute viral hepatitis or
hepatic encephalopathy;

12. ALT/AST >5 × ULN or total bilirubin >3 × ULN at Screening;

13. Receipt of any potentially-effective systemic antibiotic with activity against
Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to
randomization (exceptions defined in protocol);

14. Requirement for additional systemic antibiotic therapy (other than study drug) or
antifungal therapy for vaginal candidiasis;

15. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the
study;

16. Known history of HIV virus infection and known recent CD4 count <200/mm3;

17. Presence of significant immunodeficiency or an immunocompromised condition and
long-term use of systemic corticosteroids;

18. Presence of neutropenia;

19. Presence of thrombocytopenia;

20. A QT interval corrected using Fridericia's formula >480 msec;

21. History of significant hypersensitivity or allergic reaction to fosfomycin, any
contraindication to the use of piperacillin/tazobactam;

22. Participation in a clinical study involving investigational medication or
investigational device within the last 30 days prior to randomization;

23. Inability, in the judgment of the Investigator, to tolerate the salt load required for
study drug administration;

24. Unable or unwilling, in the judgment of the Investigator, to comply with the protocol;

25. Any patients previously randomized in this study.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Urinary Tract Infection Complicated

Acute Pyelonephritis

Urinary Tract Infection Symptomatic

Intervention(s)

Drug: ZTI-01

Drug: Piperacillin-tazobactam

Primary Outcome(s)

Number of Patients With an Overall Success [Time Frame: TOC Visit (Day 19)]

Secondary Outcome(s)

Number of Patients With a Response of Clinical Cure in Various Protocol Populations [Time Frame: TOC Visit (Day 19)]

Number of Patients With a Response of Microbiologic Eradication [Time Frame: TOC Visit (Day 19)]

Secondary ID(s)

2015-003372-73

ZTI-01-200

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Medpace, Inc.

Results

• Results available: Yes
• Date Posted: 11/12/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02753946