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

Phase 3

Completed

Conditions: Acute Pyelonephritis
Urinary Tract Infections

Interventions: Drug: Cefepime/VNRX-5133 (taniborbactam)
Drug: Meropenem

Registration Number: NCT03840148

Lead Sponsor: Venatorx Pharmaceuticals, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 661

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cefepime/VNRX-5133 (taniborbactam)	Cefepime/VNRX-5133 (taniborbactam)	Cefepime/VNRX-5133 administered q8h intravenously (IV) over a 2-hour period.
Meropenem	Meropenem	Meropenem will be administered q8h IV over 30 minutes.

Primary Outcome Measures

Name	Time	Method
Composite Success at Test of Cure (TOC) in the Microbiological Intent-to-treat (microITT) Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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

Name	Time	Method
Composite Success at Test of Cure (TOC) in the Extended Microbiological Intent-to-treat (emicroITT) Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Composite Success at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Clinical Success at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Microbiologic Success at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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 at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Composite Success at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Microbiological Success at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Microbiological Success at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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 at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Investigator Opinion of Clinical Success at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	The proportion of patients with clinical success based on investigator opinion at TOC.
Composite Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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 in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Composite Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Composite Success at End of Treatment (EOT) in the Microbiologically-Evaluable (ME) Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Microbiologic Success at End of Treatment (EOT) in the ME Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Composite Success at Test of Cure (TOC) in the ME Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Composite Success at Late Follow Up (LFU) in the ME Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Microbiologic Success at Late Follow Up (LFU) in the ME Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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 at Late Follow Up (LFU) in the CE Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Clinical Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the CE Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Microbiologic Success at Test of Cure (TOC) in the ME Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Composite Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at the End of Treatment (EOT) in the ME Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Composite Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Microbiologic Success in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the ME Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Composite Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Microbiologic Success in Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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 at End of Treatment (EOT) in the Clinically Evaluable (CE) Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Clinical Success at Test of Cure (TOC) in the CE Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Clinical Success in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the CE Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Clinical Success in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the CE Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure TOC in the ME Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the ME Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the microITT Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Test of Cure (TOC) in the microITT Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at Late Follow Up (LFU) in the microITT Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Per-Pathogen Microbiologic Eradication at End of Treatment (EOT) in the ME Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.
Per-Pathogen Microbiologic Eradication at Test of Cure (TOC) in the ME Population	Assessed at Test of Cure visit (occurred once per participant between Study Days 19 to 23)	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.
Per-Pathogen Microbiologic Eradication at Late Follow Up (LFU) in the ME Population	Assessed at Late Follow Up visit (occurred once per participant between Study Days 28 to 35)	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.
Per-Pathogen Microbiologic Eradication in Patients With Cefepime-Resistant Pathogens at End of Treatment (EOT) in the ME Population	Assessed within 24 hours after last IV dose (up to 15 days from start of treatment)	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.

Trial Locations

Locations (78): Site 184003
🇺🇸
Buena Park, California, United States
Site 184002
🇺🇸
Chula Vista, California, United States
Site 184001
🇺🇸
La Mesa, California, United States
184012
🇺🇸
Northridge, California, United States
Site 103203
🇦🇷
Córdoba, Argentina
Site 107601
🇧🇷
Belo Horizonte, Brazil
Site 107608
🇧🇷
San Paolo, Brazil
Site 110009
🇧🇬
Gabrovo, Bulgaria
Site 110002
🇧🇬
Pleven, Bulgaria
Site 110007
🇧🇬
Plovdiv, Bulgaria
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Site 184003
🇺🇸Buena Park, California, United States