Clinical trial NCT03840148: Safety and Efficacy Study of Cefepime/VNRX-5133 in Patients With Complicated Urinary Tract Infections
Official title: A 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Tract Infections
Acute Pyelonephritis
Keywords: Bacterial Infections
Cefepime
Meropenem
Complicated Urinary Tract Infections
Anti-Infective Agents
β-Lactamase Inhibitors
VNRX-5133 (taniborbactam)
Lead sponsor: Venatorx Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-02-15
Enrollment: 661
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the safety and efficacy of cefepime/VNRX-5133 compared with meropenem in both eradication of bacteria and in symptomatic response in patients with cUTIs.


Eligibility criteria: 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

Primary outcomes:
measure: Composite Success at Test of Cure (TOC) in the Microbiological Intent-to-treat (microITT) Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
Secondary outcomes:
measure: Microbiologic Success at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Clinical Success at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Composite Success at Test of Cure (TOC) in the Extended Microbiological Intent-to-treat (emicroITT) Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Composite Success at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Microbiological Success at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Clinical Success at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Composite Success at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Microbiological Success at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Clinical Success at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Investigator Opinion of Clinical Success at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Composite Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Microbiologic Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Composite Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Composite Success at End of Treatment (EOT) in the Microbiologically-Evaluable (ME) Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Microbiologic Success at End of Treatment (EOT) in the ME Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Composite Success at Test of Cure (TOC) in the ME Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Microbiologic Success at Test of Cure (TOC) in the ME Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Composite Success at Late Follow Up (LFU) in the ME Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Microbiologic Success at Late Follow Up (LFU) in the ME Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Composite Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Microbiologic Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Composite Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Microbiologic Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Clinical Success at End of Treatment (EOT) in the Clinically Evaluable (CE) Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Clinical Success at Test of Cure (TOC) in the CE Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Clinical Success at Late Follow Up (LFU) in the CE Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the CE Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the CE Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the CE Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the ME Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the ME Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the ME Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
measure: Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the ME Population
timeFrame: Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)
measure: Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure TOC in the ME Population
timeFrame: Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)
measure: Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population
timeFrame: Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)
Other outcomes:
measure: Number of Patients With Treatment-Emergent Adverse Events
timeFrame: Study Days 1 to 35
measure: Number of Patients With Serious Adverse Events
timeFrame: Study Days 1 to 35
Locations:
city: Buena Park
country: United States
facility: Site 184003
state: California
city: Chula Vista
country: United States
facility: Site 184002
state: California
city: La Mesa
country: United States
facility: Site 184001
state: California
city: Northridge
country: United States
facility: 184012
state: California
city: Córdoba
country: Argentina
facility: Site 103203
city: Belo Horizonte
country: Brazil
facility: Site 107601
city: San Paolo
country: Brazil
facility: Site 107608
city: Gabrovo
country: Bulgaria
facility: Site 110009
city: Pleven
country: Bulgaria
facility: Site 110002
city: Plovdiv
country: Bulgaria
facility: Site 110007
city: Ruse
country: Bulgaria
facility: Site 110003
city: Sofia
country: Bulgaria
facility: Site 110010
city: Sofia
country: Bulgaria
facility: Site 110004
city: Sofia
country: Bulgaria
facility: Site 110005
city: Sofia
country: Bulgaria
facility: Site 110008
city: Veliko Tarnovo
country: Bulgaria
facility: Site 110001
city: Baotou
country: China
facility: Site 156022
city: Beijing
country: China
facility: Site 156002
city: Beijing
country: China
facility: Site 156006
city: Chendu
country: China
facility: Site 156015
city: Chongqing
country: China
facility: Site 156011
city: Chongqing
country: China
facility: Site 156012
city: Dalian
country: China
facility: Site 156004
city: Fujian
country: China
facility: Site 156030
city: Guangdong
country: China
facility: Site 156014
city: Guangdong
country: China
facility: Site 156027
city: Guangzhou
country: China
facility: Site 156025
city: Guiyang
country: China
facility: Site 156018
city: Nanchang
country: China
facility: Site 156003
city: Nanjing
country: China
facility: Site 156005
city: Nanjing
country: China
facility: Site 156008
city: Nanjing
country: China
facility: Site 156007
city: Ningbo
country: China
facility: Site 156013
city: Shandong
country: China
facility: Site 156028
city: Shanghai
country: China
facility: Site 156017
city: Shijiazhuang
country: China
facility: Site 156016
city: Tianjin
country: China
facility: Site 156020
city: Xiamen
country: China
facility: Site 156010
city: Ürümqi
country: China
facility: Site 156029
city: Split
country: Croatia
facility: Site 119103
city: Zagreb
country: Croatia
facility: Site 119101
city: Zagreb
country: Croatia
facility: Site 119106
city: Budapest
country: Hungary
facility: Site 134801
city: Nyiregyhaza
country: Hungary
facility: Site 134803
city: Szeged
country: Hungary
facility: Site 134804
city: Daugavpils
country: Latvia
facility: Site 142803
city: Riga
country: Latvia
facility: Site 142804
city: Riga
country: Latvia
facility: Site 142801
city: Colima
country: Mexico
facility: Site 148402
city: Guadalajara
country: Mexico
facility: Site 148401
city: Cuzco
country: Peru
facility: Site 160403
city: Lima
country: Peru
facility: Site 160410
city: Lima
country: Peru
facility: Site 160406
city: Trujillo
country: Peru
facility: Site 160404
city: Bucharest
country: Romania
facility: Site 164204
city: Bucuresti
country: Romania
facility: Site 164206
city: Bucuresti
country: Romania
facility: Site 164205
city: Craiova
country: Romania
facility: Site 164201
city: Moscow
country: Russian Federation
facility: Site 164307
city: Penza
country: Russian Federation
facility: Site 164301
city: Pyatigorsk
country: Russian Federation
facility: Site 164308
city: Rostov-on-Don
country: Russian Federation
facility: Site 164311
city: Sankt Peterburg
country: Russian Federation
facility: Site 164303
city: Saratov
country: Russian Federation
facility: Site 164302
city: Belgrade
country: Serbia
facility: Site 189001
city: Belgrade
country: Serbia
facility: Site 189002
city: Adapazarı
country: Turkey
facility: Site 179207
city: Bornova
country: Turkey
facility: Site 179203
city: Bostanci
country: Turkey
facility: Site 179202
city: Diyarbakır
country: Turkey
facility: Site 179204
city: Çankaya
country: Turkey
facility: Site 179205
city: Dnipro
country: Ukraine
facility: Site 180404
city: Ivano-Frankivs'k
country: Ukraine
facility: Site 180408
city: Kharkiv
country: Ukraine
facility: Site 180402
city: Kyiv
country: Ukraine
facility: Site 180406
city: Luts'k
country: Ukraine
facility: Site 180401
city: Vinnytsia
country: Ukraine
facility: Site 180403
city: Zaporizhzhya
country: Ukraine
facility: Site 180407
Study officials:
References: