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

Urinary Tract Infections Clinical Trial

— CERTAIN-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03840148
• Other study ID #: VNRX-5133-201
• Secondary ID: 2018-001451-13
• Status: Completed
• Phase: Phase 3
• Start date: August 7, 2019
• Est. completion date: December 14, 2021

Study information

• Verified date: February 2024
• Source: Venatorx Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 661
• Est. completion date: December 14, 2021
• Est. primary completion date: December 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Pyelonephritis
• Communicable Diseases
• Infections
• Pyelonephritis
• Urinary Tract Infections

Intervention

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 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.

Locations

Country	Name	City	State
Argentina	Site 103203	Córdoba
Brazil	Site 107601	Belo Horizonte
Brazil	Site 107608	San Paolo
Bulgaria	Site 110009	Gabrovo
Bulgaria	Site 110002	Pleven
Bulgaria	Site 110007	Plovdiv
Bulgaria	Site 110003	Ruse
Bulgaria	Site 110004	Sofia
Bulgaria	Site 110005	Sofia
Bulgaria	Site 110008	Sofia
Bulgaria	Site 110010	Sofia
Bulgaria	Site 110001	Veliko Tarnovo
China	Site 156022	Baotou
China	Site 156002	Beijing
China	Site 156006	Beijing
China	Site 156015	Chendu
China	Site 156011	Chongqing
China	Site 156012	Chongqing
China	Site 156004	Dalian
China	Site 156030	Fujian
China	Site 156014	Guangdong
China	Site 156027	Guangdong
China	Site 156025	Guangzhou
China	Site 156018	Guiyang
China	Site 156003	Nanchang
China	Site 156005	Nanjing
China	Site 156007	Nanjing
China	Site 156008	Nanjing
China	Site 156013	Ningbo
China	Site 156028	Shandong
China	Site 156017	Shanghai
China	Site 156016	Shijiazhuang
China	Site 156020	Tianjin
China	Site 156029	Ürümqi
China	Site 156010	Xiamen
Croatia	Site 119103	Split
Croatia	Site 119101	Zagreb
Croatia	Site 119106	Zagreb
Hungary	Site 134801	Budapest
Hungary	Site 134803	Nyiregyhaza
Hungary	Site 134804	Szeged
Latvia	Site 142803	Daugavpils
Latvia	Site 142801	Riga
Latvia	Site 142804	Riga
Mexico	Site 148402	Colima
Mexico	Site 148401	Guadalajara
Peru	Site 160403	Cuzco
Peru	Site 160406	Lima
Peru	Site 160410	Lima
Peru	Site 160404	Trujillo
Romania	Site 164204	Bucharest
Romania	Site 164205	Bucuresti
Romania	Site 164206	Bucuresti
Romania	Site 164201	Craiova
Russian Federation	Site 164307	Moscow
Russian Federation	Site 164301	Penza
Russian Federation	Site 164308	Pyatigorsk
Russian Federation	Site 164311	Rostov-on-Don
Russian Federation	Site 164303	Sankt Peterburg
Russian Federation	Site 164302	Saratov
Serbia	Site 189001	Belgrade
Serbia	Site 189002	Belgrade
Turkey	Site 179207	Adapazari
Turkey	Site 179203	Bornova
Turkey	Site 179202	Bostanci
Turkey	Site 179205	Çankaya
Turkey	Site 179204	Diyarbakir
Ukraine	Site 180404	Dnipro
Ukraine	Site 180408	Ivano-Frankivs'k
Ukraine	Site 180402	Kharkiv
Ukraine	Site 180406	Kyiv
Ukraine	Site 180401	Luts'k
Ukraine	Site 180403	Vinnytsia
Ukraine	Site 180407	Zaporizhzhya
United States	Site 184003	Buena Park	California
United States	Site 184002	Chula Vista	California
United States	Site 184001	La Mesa	California
United States	184012	Northridge	California

Sponsors (1)

Lead Sponsor	Collaborator
Venatorx Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  China,  Croatia,  Hungary,  Latvia,  Mexico,  Peru,  Romania,  Russian Federation,  Serbia,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with adverse events	Percent of participants experiencing adverse events.	Days 35
Other	Number of participants with serious adverse events	Percent of participants experiencing serious adverse events.	Days 35
Primary	Composite of microbiological eradication and symptomatic clinical success in the microbiological intent-to-treat (microITT) population at test of cure (TOC)	Microbiologic eradication is 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.	Days 19-23
Secondary	Microbiological and symptomatic success at test of cure (TOC)	The proportion of patients with both microbiological success and symptomatic clinical success at TOC in the extended microITT population.	Days 19-23
Secondary	Clinical and microbiological success at end of treatment (EOT) and last follow-up (LFU)	The proportion of patients with both microbiological success and symptomatic clinical success at EOT and LFU.	24 hours after last IV dose, Days 28-35
Secondary	Per-patient microbiological success at EOT, TOC and LFU	The proportion of patients with per-patient microbiological success at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35
Secondary	Patients with symptomatic clinical success at EOT, TOC and LFU	The proportion of patients with symptomatic clinical success at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35
Secondary	Investigator opinion of clinical success at TOC	The proportion of patients with clinical success based on investigator opinion at TOC.	Days 19-23
Secondary	Per-pathogen microbiological success at EOT, TOC and LFU	The proportion of patients with per-pathogen microbiological success at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35
Secondary	Microbiological and clinical success in cefepime-resistant pathogens at EOT, TOC and LFU	The proportion of patients with both microbiological success and symptomatic clinical success among those with cefepime-resistant pathogens at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35
Secondary	Per-patient microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU	The proportion of patients with per-patient microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35
Secondary	Per-pathogen microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU	The proportion of patients with per-pathogen microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35
Secondary	Symptomatic clinical success among those with cefepime-resistant pathogens at EOT, TOC and LFU cefepime-resistant pathogens	The proportion of patients with symptomatic clinical success among those with cefepime-resistant pathogens at EOT, TOC and LFU.	Within 24 hours of last IV dose, Days 19-23, Days 28-35