Complicated urinary tract infections including acute pyelonephritis MedDRA version: 20.1 Level: PT Classification code 10037597 Term: Pyelonephritis acute System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: cefepime-enmetazobactam
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Enmetazobactam
CAS Number: 1001404-83-6
Concentration unit: mg milligra
Sponsors
Allecra Therapeutics SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be from birth to 10 cells/µL in unspun urine or =10 cells/high power field in spun urine. b) If 5 cells/µL in unspun urine or =5 cells/high power field in spun urine. 7. Participant demonstrates clinical signs and/or symptoms of either acute pyelonephritis or cUTI at the Screening Visit, as defined by the following criteria: a. For pyelonephritis, participants must have at least 2 of the following new or worsening signs and/or symptoms: i. If 0 to <2 years of age: • Fever (as defined by the investigator) • Failure to thrive • Recent weight loss • Irritability • Poor feeding • Lack of normal level of activity • Abdominal tenderness on physical examination • Vomiting ii. If 2 to <18 years of age: • Fever (as defined by the investigator) • Dysuria • Urinary urgency • Urinary frequency • New-onset urinary incontinence • Suprapubic pain, flank pain, or abdominal pain • Suprapubic tenderness or CVA tenderness on physical examination • Nausea or vomiting OR b. For cUTI, participants must have at least 2 of the new or worsening signs and/or symptoms listed above AND must have at least 1 of the following complicating factors: • Obstructive uropathy • Congenital, functional, or anatomic abnormality of the urogenital tract • Temporary indwelling urinary catheter • Bladder instrumentation within <24 hours • Recurrent UTI (=2 events within a 12-mo
Exclusion criteria
Exclusion criteria: 1. History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to cefepime, any cephalosporin, penicillins, ß-lactamase inhibitors (e.g., tazobactam, sulbactam, or clavulanic acid), or other ß-lactam agents. 2. Previous enrolment in this study, or in another interventional study =30 days before i.v. administration of study intervention. 3. Concurrent infection requiring systemic antibiotics in addition to the i.v. study intervention therapy at the time of first study intervention administration. 4. Receipt of systemic antibiotics within 24 hours before obtaining the study qualifying pre-treatment baseline urine sample and before study intervention therapy. Exceptions are: • Receipt up to 24 hours of short-acting antibacterial agent with a daily dose not completed. • Patients who received prior antimicrobial therapy for the current cUTI/AP, and 1) in the Investigator’s opinion, failed that prior antibiotic therapy (i.e., presented with worsening signs and symptoms), AND 2) were documented that the pathogen is non-susceptible to the prior antibiotic therapy. • Patients who have received antimicrobial prophylaxis for recurrent cUTI and then presented signs and symptoms consistent with an active new cUTI or AP. 5. A permanent indwelling bladder catheter or instrumentation including nephrostomy or current urinary catheter or anticipation of urinary catheter placement that would not be removed during the course of i.v. study intervention therapy administration. 6. Participant has suspected or known complete obstruction of any portion of the urinary tract, perinephric abscess, or ileal loops. 7. Participant has trauma to the pelvis or urinary tract. 8. Participant has undergone renal transplantation. 9. Participant has a condition or history of any illness that, in the opinion of the investigator, would have made the participant unsuitable for the study (e.g., may have confounded the results of the study or posed additional risk in administering the study therapy to the participant). 10. Participant is considered unlikely to survive the 6-week study period or had a rapidly progressive illness, including septic shock, that was associated with a high risk of mortality. 11. At the time of first study intervention administration, known presence of a cUTI caused by pathogens resistant to Cefepime - enmetazobactam. 12. Presence of any of the following clinically significant laboratory abnormalities: a. Haematocrit 3 times the age-specific upper limit of normal (ULN), or total bilirubin >2 times ULN (except known Gilbert’s disease) and Absolute Neutrophil count<1000/ mm3. c. eGFR <30 mL/min/1.73m2. (updated creatinine-based “Bedside Schwartz”) 13. Participant has baseline QTcB (corrected Bazett’s formula) of greater than 450 msec. 14. History of seizures, excluding well-documented febrile seizures of childhood. 15. If female, currently pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are to determine the pharmacokinetics, safety, and tolerability of cefepime-enmetazobactam in all paediatric population subsets from birth to less than 18 years of age with cUTI .;Secondary Objective: The secondary objectives of this study are to assess efficacy of the combination of cefepime-enmetazobactam in all paediatric population subsets from birth to less than 18 years of age with cUTI.;Primary end point(s): •Cmax, Tmax, AUC0-tau (repeat dose), AUC0-inf, t1/2, ?z, CL, Vd, Cmin. •Treatment emergent adverse events including monitoring of adverse events of special interests: o Any increase in ALT or AST >3 times the age-specific upper limit of normal or total bilirubin >2 times ULN. o Clostridium difficile-associated diarrhoea (CDAD)/Pseudomembranous colitis o Hypersensitivity reactions, anaphylactic reactions, angioedema o Encephalopathy/ seizures / convulsions/delirium •Laboratory parameters, ECGs, vital signs, and physical examination ;Timepoint(s) of evaluation of this end point: The treatment duration will be 3 - 7 days, depending on the time needed for disappearance of symptoms of the infection. The participant will be hospitalized at least during the treatment administration period. After the last administration of cefepime and enmetazobactam, there will be the end of treatment visit (EOT), then 2 follow-up visits at 7 days (Test of Cure (TOC)), then 14 days (Late Follow-up (LFU)) after the end of treatment visit. The End of study Visit (EOS) will be conducted via telephone call (or a visit deemed necessary as per the investigator) 28 days after the EOT visit. The participants may be discharged from hospital at the discretion of the investigator after the end of treatment visit but will be required to return to the hospital for the 2 follow-up visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall Response (composite of clinical and microbiological outcome) • Clinical response • Microbiological response ;Timepoint(s) of evaluation of this end point: Day 3 or 7, EOT, TOC, LFU are the timepoints for the secondary endpoints. | — |
Countries
Czechia, Czech Republic, France, Hungary, Poland, Slovakia, Spain
Contacts
Public ContactHead of Regulatory Affairs
Allecra Therapeutics SAS
Outcome results
None listed