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

March 5, 2019 updated by: Nabriva Therapeutics AG

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

The purpose of the study is to demonstrate the safety and efficacy of ZTI-01 (IV fosfomycin) as non-inferior to piperacillin/tazobactam in overall success (clinical cure and microbiologic eradication) for the treatment of hospitalized patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multi-center, randomized, double-blind, parallel-group study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of ZTI-01 (IV fosfomycin) compared to piperacillin/tazobactam in the treatment of hospitalized adults with cUTI or AP. Diagnosed and prescreened hospitalized patients will be randomized 1:1 to receive one of two intravenous treatments: 6 g ZTI-01 three times daily (18g total daily dose) or 4.5 g piperacillin/tazobactam three times daily (13.5g total daily dose) for 7 calendar days, with option to extend treatment up to 14 days in patients with positive blood culture at pretreatment. Patients will participate in the study for approximately 26 days. Urine cultures will be obtained and organisms quantified for qualified patients at baseline, during treatment, at end of treatment (EOT), at test of cure (TOC) and late follow up visits (LFU). Blood cultures will be obtained at baseline and repeated if positive throughout the study. Safety and efficacy evaluations will include vital signs, labs, physical exams, ECG and overall response as evaluated by the Investigator. Pharmacokinetic samples will be obtained (sparse sampling) for all patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
465

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Brest, Belarus
      • Gomel, Belarus
      • Grodno, Belarus
      • Minsk, Belarus
      • Vitebsk, Belarus
  • Bulgaria
      • Plovdiv, Bulgaria
      • Sofia, Bulgaria
  • Croatia
      • Slavonski Brod, Croatia
      • Split, Croatia
      • Zagreb, Croatia
  • Czechia
      • Brno, Czechia
      • Hradec Kralove, Czechia
      • Liberec, Czechia
  • Estonia
      • Kohtla Jarve, Estonia
      • Tallinn, Estonia
  • Georgia
      • Batumi, Georgia
      • Kutaisi, Georgia
      • Tbilisi, Georgia
  • Greece
      • Ambelokipoi, Greece
      • Athens, Greece
      • Thessaloníki, Greece
  • Hungary
      • Budapest, Hungary
      • Miskolc, Hungary
      • Nagykanizsa, Hungary
      • Pecs, Hungary
      • Szekszard, Hungary
      • Szentes, Hungary
  • Latvia
      • Riga, Latvia
      • Valmiera, Latvia
  • Lithuania
      • Kaunas, Lithuania
      • Klaipeda, Lithuania
      • Vilnius, Lithuania
  • Poland
      • Bielsko-Biala, Poland
      • Krakow, Poland
      • Lodz, Poland
      • Piaseczno, Poland
      • Tychy, Poland
      • Wrocław, Poland
      • Zamosc, Poland
  • Romania
      • Bucharest, Romania
      • Craiova, Romania
      • Oradea, Romania
  • Russian Federation
      • Krasnoyarsk, Russian Federation
      • Moscow, Russian Federation
      • Moscow, Zelenograd, Russian Federation
      • Nizhny Novgorod, Russian Federation
      • Novosibirsk, Russian Federation
      • Penza, Russian Federation
      • Rostov-On-Don, Russian Federation
      • Saratov, Russian Federation
      • Smolensk, Russian Federation
      • St Petersburg, Russian Federation
      • St. Petersburg, Russian Federation
      • Vsevolozhsk, Russian Federation
  • Slovakia
      • Martin, Slovakia
      • Poprad, Slovakia
      • Zilina, Slovakia
  • Ukraine
      • Chernihiv, Ukraine
      • Dnipropetrovsk, Ukraine
      • Kharkiv, Ukraine
      • Kyiv, Ukraine
      • Odesa, Ukraine
      • Zaporizhzhia, Ukraine
  • United States
    • Florida
      • Pensacola, Florida, United States
    • Georgia
      • Augusta, Georgia, United States
      • Columbus, Georgia, United States
    • Massachusetts
      • Boylston, Massachusetts, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • Montana
      • Butte, Montana, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ZTI-01
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
Drug: ZTI-01
6g ZTI-01 intravenous infusion TID q8 hours
Other Names:
  • disodium fosfomycin
Active Comparator: piperacillin tazobactam
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Drug: Piperacillin-tazobactam
4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
Other Names:
  • piperacillin-tazobactam combination product

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Patients With an Overall Success
Time Frame: TOC Visit (Day 19)
Clinical cure (resolution or significant improvement in signs and symptoms) and microbiologic eradication (baseline pathogen) in m-MITT population
TOC Visit (Day 19)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Patients With a Response of Clinical Cure in Various Protocol Populations
Time Frame: TOC Visit (Day 19)
mMITT
TOC Visit (Day 19)
Number of Patients With a Response of Microbiologic Eradication
Time Frame: TOC Visit (Day 19)
mMITT
TOC Visit (Day 19)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nabriva Therapeutics AG

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medpace, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Evelyn J Ellis-Grosse, PhD, Zavante Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 12, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 7, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZTI-01-200
  • 2015-003372-73 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Individual IPD data will be shared in listings with FDA, IRB/ECs, Data Monitoring Committee

IPD Sharing Time Frame

ongoing submissions to IND

IPD Sharing Access Criteria

IND/NDA submission, CTA submissions

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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