None listed
Conditions
Interventions
Experimental Arm Type of group
Patients randomized to cefepime/VNRX-5133 will receive meropenem placebo IV immediately followed by cefepime/VNRX-5133 (2 g/0.5 g IV q8h). Meropenem placebo will be administered via IV pump over 30 minutes. Cefepime/VNRX-5133 will be administered via IV pump over a 2-hour period.
Group name:Comparator Arm Type of group
Patients randomized to receive meropenem will also receive cefepime/VNRX-5133 placebo IV immediately following meropenem (1 g IV q8h). Meropenem will be infused over 30 minutes. Cefepime/VNRX-5133 placebo will be administered via IV pump over a 2-hour period.
Sponsors
VenatoRx Pharmaceuticals, Inc. (VenatoRx),
Eligibility
Inclusion criteria
Inclusion criteria: 1. Provide signed informed consent 2. Adult male or female, ≥18 years of age 3. If female, meets at least 1 of the following criteria: • Surgically sterile • Age ≥50 years and postmenopausal for ≥12 months • Age 10 cells/μL in unspun urine • WBC >10 cells/μL in urine sediment 5. Demonstrates either AP or complicated lower UTI as defined by the following criteria: a. AP is indicated by the presence of both of the following criteria: • At least 1 of the following is present: o Nausea or vomiting o Chills or rigors or warmth associated with fever, defined as body temperature >38°C • Has flank pain or costovertebral angle tenderness b. Complicated lower UTI is indicated by the presence of all 3 of the following criteria: • At least 1 of the following is present: o Nausea or vomiting o Chills or rigors or warmth associated with fever, defined as body temperature >38°C • At least 1 of the following signs/symptoms is present: o Dysuria o Urinary urgency o Urinary frequency o Pelvic pain or suprapubic tenderness/pelvic tenderness • At least 1 of the following complicating factors is present: o Chronic urinary retention o Obstructive uropathy (if complete obstruction, should intend to relieve obstruction within 48 hours after randomization) o Neurogenic bladder with presence or history of urine residual volume of >100 mL o Indwelling catheter (with expectation for permanent discontinuation of the catheter by Study Day 5) 6. Requires IV antibacterial therapy as initial treatment for cUTI
Exclusion criteria
Exclusion criteria: 1. Receipt of effective antibacterial drug therapy for cUTI for a continuous duration of more than 24 hours during the previous 72 hours prior to randomization 2. Where a urine culture result is available: • At least 1 uropathogen at ≥105 colony forming units per milliliter (CFU/mL) is resistant to meropenem, or • A gram-negative bacterial pathogen is not identified • More than 2 microorganisms are isolated regardless of the colony count, or • The patient has a confirmed fungal UTI with colony count ≥103 CFU/mL 3. Requirement for use of nonstudy systemic antibacterial drug therapy that would have a potential effect on outcome evaluations in patients with cUTI 4. Patients with suspected or confirmed prostatitis or urinary tract symptoms attributable to a sexually transmitted disease 5. Patients with perinephric or renal abscess 6. Patients with renal transplantation or receiving hemodialysis or peritoneal dialysis 7. Patients with urinary diversions (e.g., ileal loops, cutaneous urostomy) 8. Patients who may need ongoing antibacterial drug prophylaxis after treatment of cUTI (such as vesico-ureteral reflux) 9. Any recent history of trauma to the pelvis or urinary tract 10. Patient has any urinary catheter or device or foreign body that will not be discontinued by Study Day 5, including but not limited to indwelling bladder catheter, urinary catheter, nephrostomy tubes, or stent 11. Patient is unlikely to respond to 7 days of antibacterial therapy for the treatment of cUTI without bacteremia or up to 14 days of therapy for treatment of cUTI with bacteremia 12. Patient has acute hepatitis, cirrhosis (Child-Pugh Class B or C), acute hepatic failure, or acute decompensation of chronic hepatic failure 13. Patient has had a heart, lung, heart-lung, or pancreatic transplant at any time; or bone marrow transplant in the preceding year 14. Patient has any of the following laboratory values: • Estimated glomerular filtration rate (eGFR) 3.0× the upper limit of normal (ULN), unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert’s disease aminotransferase (AST) >3.0× ULN at screening. Patients with values >3.0× ULN and 3.0× ULN. Patients with values >3.0× ULN and <5.0× ULN are eligible if this value is acute and documented as being directly related to the infectious process being treated. 15. Patient has a history of serious hypersensitivity (e.g., anaphylaxis), serious allergy, or any serious reaction to cephalosporin, penicillin, carbapenem, or other β-lactam antibacterials 16. Patient is considered unlikely to survive the 4- to 5-week study period or have a rapidly progressive or terminal illness, including septic shock, that is associated with a high risk of mortality 17. Patient requires concomitant medication with valproic acid or divalproex investigator’s opinion, may interfere with optimal participation in the study, or is unlikely to comply with protocol (e.g., inability to fully comprehend and clearly respond
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Microbiologic response is assessed by obtaining a urine culture from a clean catch to ensure that any bacteria that were causing the urine infection have been eradicated. Clinical response is assessed using a set of questions related to the patients symptoms and comparing that to the same questions that were answered at the time of study entry about the symptoms they have when they are not ill with a urine infection to see if they have returned to the same state. Measure:Demonstration of microbiological success and clinical symptoms success at TOC in the microbiological intent-to-treat (microITT) population. Timepoints:At the test of cure visit, performed between study Day 19 and study Day 23. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:• The proportion of patients with both microbiological success and symptomatic clinical success at TOC in the extended microITT population • The proportion of patients with per-patient microbiological success at TOC in the microbiologically evaluable (ME)-TOC population • The proportion of patients with symptomatic clinical success at TOC in the clinically evaluable (CE)-TOC and ME-TOC populations • The proportion of patients with clinical success based on investigator opinion at EOT, TOC, and LFU in the microITT and relevant CE and ME populations • The proportion of patients with per-patient microbiological success at EOT and LFU in the microITT, ME-EOT, and ME-LFU populations • The proportion of patients with symptomatic clinical success at EOT and LFU in the microITT, CE-EOT, ME-EOT, CE-LFU, and ME-LFU populations • The proportion of patients with per-pathogen microbiological success in the microITT, ME-EOT, ME-TOC, and ME-LFU populations • The proportion of patients with per-patient microbiological success among those with cefepime-resistant pathogens in the microITT, ME-EOT, ME-TOC, and ME-LFU populations • The proportion of patients with per-pathogen microbiological success among those with cefepime-resistant pathogens in the microITT, ME-EOT, ME-TOC, and ME-LFU populations • The proportion of patients with symptomatic clinical success among those with cefepime-resistant pathogens in the microITT, CE-EOT, CE-TOC, CE-LFU, ME-EOT, ME-TOC, and ME-LFU populations Measure:Clinical and Microbiological Efficacy Timepoints:These secondary endpoints will be evaluated at the end of treatment (EOT), test of cure (TOC) and late follow-up (LFU) visits. ; Outcome name:Safety and tolerability will be assessed based on the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), exposure, mortality, reasons for discontinuation of study drug and study withdrawal, vital sign me | — |
Countries
Argentina, Brazil, Bulgaria, China, Croatia, Czech Republic, Hungary, Latvia, Mexico, Peru, Romania, Russian Federation, Serbia, Turkey, Ukraine, United States
Contacts
Public ContactFlor de Liz Jacome
Labcorp Peru Services S.A
Outcome results
None listed