Safety and Efficacy Study of Cefepime/VNRX-5133 in Patients With Complicated Urinary Tract Infections

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified May 2025 by Venatorx Pharmaceuticals, Inc.
Sponsor
Venatorx Pharmaceuticals, Inc.
Information Provided by (Responsible Party)
Venatorx Pharmaceuticals, Inc.
Clinicaltrials.gov Identifier
NCT03840148
Other Study ID Numbers:
VNRX-5133-201
First Submitted
February 5, 2019
First Posted
February 14, 2019
Results First Posted
March 22, 2024
Last Update Posted
June 5, 2025
Last Verified
May 2025

ClinicalTrials.gov processed this data on June 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Urinary Tract InfectionsAcute Pyelonephritis
Drug: Cefepime/VNRX-5133 (taniborbactam)Drug: Meropenem

Study Design

Study TypeInterventional
Actual Enrollment661 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-blind, Active Controlled Noninferiority Study Evaluating the Efficacy, Safety, and Tolerability of Cefepime/VNRX-5133 in Adults With Complicated Urinary Tract Infections (cUTI), Including Acute Pyelonephritis
Study Start DateAugust 6, 2019
Actual Primary Completion DateDecember 13, 2021
Actual Study Completion DateDecember 13, 2021

Groups and Cohorts

Group/CohortIntervention/Treatment
Cefepime/VNRX-5133 (taniborbactam)
Cefepime/VNRX-5133 administered q8h intravenously (IV) over a 2-hour period.
Drug: Cefepime/VNRX-5133 (taniborbactam)
Cefepime/VNRX-5133 administered q8h intravenously (IV) over a 2-hour period for 7 days (up to 14 days for patients with bacteremia). Patients will also receive meropenem placebo administered via IV over 30 minutes.
Meropenem
Meropenem will be administered q8h IV over 30 minutes.
Drug: Meropenem
Meropenem will be administered q8h IV over 30 minutes for 7 days (up to 14 days for patients with bacteremia). Patients will also receive cefepime/VNRX-5133 placebo administered via IV over a 2-hour period.

Outcome Measures

Primary Outcome Measures
  1. Composite Success at Test of Cure (TOC) in the Microbiological Intent-to-treat (microITT) Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
Secondary Outcome Measures
  1. Microbiologic Success at Test of Cure (TOC) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  2. Clinical Success at Test of Cure (TOC) in the microITT Population
    Symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  3. Composite Success at Test of Cure (TOC) in the Extended Microbiological Intent-to-treat (emicroITT) Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  4. Composite Success at End of Treatment (EOT) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  5. Microbiological Success at End of Treatment (EOT) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  6. Clinical Success at End of Treatment (EOT) in the microITT Population
    Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  7. Composite Success at Late Follow Up (LFU) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  8. Microbiological Success at Late Follow Up (LFU) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  9. Clinical Success at Late Follow Up (LFU) in the microITT Population
    Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  10. Investigator Opinion of Clinical Success at Test of Cure (TOC) in the microITT Population
    The proportion of patients with clinical success based on investigator opinion at TOC.
  11. Composite Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  12. Microbiologic Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  13. Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
    Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  14. Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  15. Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  16. Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
    Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  17. Composite Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  18. Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  19. Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
    Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  20. Composite Success at End of Treatment (EOT) in the Microbiologically-Evaluable (ME) Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  21. Microbiologic Success at End of Treatment (EOT) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  22. Composite Success at Test of Cure (TOC) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  23. Microbiologic Success at Test of Cure (TOC) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  24. Composite Success at Late Follow Up (LFU) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  25. Microbiologic Success at Late Follow Up (LFU) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  26. Composite Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  27. Microbiologic Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  28. Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  29. Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  30. Composite Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  31. Microbiologic Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
    Microbiologic success is eradication defined as demonstration that any gram-negative bacterial pathogen found at study entry (≥10\^5 CFU/mL) is eradicated to \<10\^3 CFU/mL.
  32. Clinical Success at End of Treatment (EOT) in the Clinically Evaluable (CE) Population
    Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  33. Clinical Success at Test of Cure (TOC) in the CE Population
    Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  34. Clinical Success at Late Follow Up (LFU) in the CE Population
    Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  35. Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the CE Population
    Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  36. Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the CE Population
    Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  37. Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the CE Population
    Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI.
  38. Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the microITT Population
    Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  39. Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the microITT Population
    Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  40. Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the microITT Population
    Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  41. Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
    Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  42. Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
    Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  43. Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
    Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  44. Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the ME Population
    Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  45. Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the ME Population
    Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  46. Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the ME Population
    Per-pathogen eradication by baseline gram-negative pathogens. The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  47. Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the ME Population
    Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  48. Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure TOC in the ME Population
    Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.
  49. Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
    Per-pathogen eradication by baseline gram-negative pathogens (only pathogens identified 10 or more times are reported). The number analyzed corresponds to the number of specified pathogens. The number is the percent of the specified pathogen identified at baseline in each treatment group that had been eradicated.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Adult male and female
Documented diagnosis of pyuria
Documented diagnosis of cUTI or Acute Pyelonephritis (AP)
Exclusion Criteria
Receipt of effective antibacterial drug therapy for cUTI for more than 24 hours during the previous 72 hours prior to randomization
A urine culture result is resistant to meropenem or a gram negative pathogen is not identified or more than 2 microorganisms are isolated or a confirmed fungal UTI is identified
Required use of nonstudy systemic bacterial therapy
Suspected or confirmed prostatitis or urinary tract symptoms attributable to sexually transmitted disease
Patients with perinephric or renal abscess
Patients with renal transplantation or receiving hemodialysis or peritoneal dialysis
Abnormal labs

Contacts and Locations

Sponsors and CollaboratorsVenatorx Pharmaceuticals, Inc.
Locations
Site 184003 | Buena Park California, United States, 90620Site 184002 | Chula Vista California, United States, 91911Site 184001 | La Mesa California, United States, 91942184012 | Northridge California, United States, 91324Site 103203 | Córdoba , Argentina, X5016KEHSite 107601 | Belo Horizonte , Brazil, 30150-221Site 107608 | São Paulo , Brazil, 04039-901Site 110009 | Gabrovo , Bulgaria, 5300Site 110002 | Pleven , Bulgaria, 5800Site 110007 | Plovdiv , Bulgaria, 4003Site 110003 | Rousse , Bulgaria, 7002Site 110010 | Sofia , Bulgaria, 1407Site 110004 | Sofia , Bulgaria, 1606Site 110005 | Sofia , Bulgaria, 1606Site 110008 | Sofia , Bulgaria, 1606Site 110001 | Veliko Tarnovo , Bulgaria, 5000Site 156022 | Baotou , China, 014010Site 156002 | Beijing , China, 100034Site 156006 | Beijing , China, 100050Site 156015 | Chendu , China, 610041Site 156011 | Chongqing , China, 400016Site 156012 | Chongqing , China, 400038Site 156004 | Dalian , China, 116023Site 156030 | Fujian , China, 362202Site 156014 | Guangdong , China, 515041Site 156027 | Guangdong , China, 518035Site 156025 | Guangzhou , China, 510120Site 156018 | Guiyang , China, 550002Site 156003 | Nanchang , China, 330006Site 156005 | Nanjing , China, 156005Site 156008 | Nanjing , China, 210008Site 156007 | Nanjing , China, 210009Site 156013 | Ningbo , China, 315010Site 156028 | Shandong , China, 276000Site 156017 | Shanghai , China, 200025Site 156016 | Shijiazhuang , China, 050000Site 156020 | Tianjin , China, 300192Site 156029 | Ürümqi , China, 830054Site 156010 | Xiamen , China, 361003Site 119103 | Split , Croatia, 21000Site 119101 | Zagreb , Croatia, 10000Site 119106 | Zagreb , Croatia, 10000Site 134801 | Budapest , Hungary, 1204Site 134803 | Nyíregyháza , Hungary, 4400Site 134804 | Szeged , Hungary, 6725Site 142803 | Daugavpils , Latvia, LV-5417Site 142804 | Riga , Latvia, LV-1002Site 142801 | Riga , Latvia, LV-1038Site 148402 | Colima , Mexico, 28018Site 148401 | Guadalajara , Mexico, 44280Site 160403 | Cuzco , Peru, 84Site 160410 | Lima , Peru, 29Site 160406 | Lima , Peru, 41Site 160404 | Trujillo , Peru, TRUJ 01Site 164206 | Bucharest , Romania, 010825Site 164205 | Bucharest , Romania, 020125Site 164204 | Bucharest , Romania, 050653Site 164201 | Craiova , Romania, 200642Site 164307 | Moscow , Russia, 117593Site 164301 | Penza , Russia, 440026Site 164308 | Pyatigorsk , Russia, 357500Site 164311 | Rostov-on-Don , Russia, 344011Site 164303 | Saint Petersburg , Russia, 194044Site 164302 | Saratov , Russia, 410054Site 189001 | Belgrade , Serbia, 11000Site 189002 | Belgrade , Serbia, 11080Site 179207 | Adapazarı , Turkey (Türkiye), 54100Site 179203 | Bornova , Turkey (Türkiye), 35040Site 179202 | Bostancı , Turkey (Türkiye), 61080Site 179205 | Çankaya , Turkey (Türkiye), 06800Site 179204 | Diyarbakır , Turkey (Türkiye), 21280Site 180404 | Dnipro , Ukraine, 49005Site 180408 | Ivano-Frankivsk , Ukraine, 76014Site 180402 | Kharkiv , Ukraine, 6111Site 180406 | Kyiv , Ukraine, 02125Site 180401 | Lutsk , Ukraine, 43000Site 180403 | Vinnytsia , Ukraine, 21018Site 180407 | Zaporizhzhya , Ukraine, 69600
Study Documents (Full Text)
Documents provided by Venatorx Pharmaceuticals, Inc.: Study Protocol  December 9, 2019Documents provided by Venatorx Pharmaceuticals, Inc.: Statistical Analysis Plan  February 1, 2022