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 -
Conditions
Interventions
Product Code: AAI101
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: NA
CAS Number: 1001404-83-6
Current Spon
Sponsors
Allecra Therapeutics SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients =18 years of age at the time of signing of informed consent; 2. Expectation that the patient’s cUTI or AP will require hospitalization and initial treatment withat least 7 days of i.v. antibiotics; 3. Female patients who are no longer of childbearing potential must meet 1 of the following criteria: (a) Women =50 years of age who are considered post-menopausal as they have beenamenorrhoeic for =12 months following cessation of all pharmaceutical or exogenoushormonal treatment; (b) Women 10 cells/mm3 in unspun urine or =10 cells/high power field in spun urine sediment; or (b) Urinalysis/dipstick analysis positive for leukocyte esterase; 7. Clinical signs and/or symptoms of cUTI (Complicated Urinary Tract Infection) or AP (Acute Pyelonephritis), as defined in Protocol, Table 1; NOTE: If the criteria for both cUTI and AP are met, the infection type will be considered cUTI for randomization and analysis purposes. 8. Have a baseline urine culture specimen obtained within
Exclusion criteria
Exclusion criteria: 1. Known urine culture with Gram positive primary pathogen at > or = 10[5] colony-forming units (CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note: Gram staining is optional) 2. History of significant hypersensitivity or allergic reaction to cefepime, piperacillin/tazobactam, any of the excipients used in the respective formulations, any beta lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams), or any BLIs (e.g., tazobactam, sulbactam, or clavulanic acid); 3. In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period; 4. Weight >180 kg; 5. Concurrent infection that would interfere with evaluation of response to the study antibiotics; 6. Need for or receipt of concomitant systemic antimicrobial agents after signing of informed consent, in addition to those designated in the study-treatment groups, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis; 7. Receipt of potentially effective systemic antibacterial therapy for a continuous duration of >24 hours during the previous 72 hours before the study-qualifying baseline urine is obtained (Exception defined in Protocol, Exc. Criteria 7) 8. Complicated urinary tract infection (UTI) known at study entry to be caused by pathogens resistant to the study antibiotics; 9. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient’s participation in the study; 10. Intractable UTI at baseline that the Investigator anticipates would require >14 days of study drug therapy; 11. Complete, permanent obstruction of the urinary tract that is not anticipated to be medically or surgically relieved during i.v. study therapy and before EOT; 12. Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter; 13. Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy. (Explained in Protocol, Exc. Criteria 13) 14. Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination; 15. Impairment of renal function with estimated glomerular filtration rate <30 mL/min/1.73 m2 calculated by the 4-variable Modification of Diet in Renal Disease (MDRD) study equation (see Appendix D); 16. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy prior to EOT); 17. Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of study data; 18. Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure and respiratory failure; 19. Presence of sepsis, producing life-threatening organ dysfunction, defined as =2 of the following criteria: a. Systolic blood pressure =100 mmHg that is not responsive to fluid challenge; b. Respi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy of cefepime-AAI101 compared to Piperacillin/Tazobactam in the treatment of cUTI, including acute pyelonephritis (AP).; Secondary Objective: The secondary objectives of this study are the following: • To assess the safety and tolerability of cefepime-AAI101 in hospitalized patients with cUTI or AP; and • To characterize the PK of cefepime-AAI101 in patients with cUTI or AP. ;Primary end point(s): The primary efficacy parameter is the proportion of patients in the Microbiological Modified Intent-to-Treat (m-MITT) Population who achieve overall treatment success at TOC.;Timepoint(s) of evaluation of this end point: “Test of Cure” is the time point. All patients will be treated for a minimum of 7 days; however, treatment may continue for up to 14 days for patients with a positive blood culture at baseline at the discretion of the Investigator. A Test of Cure (TOC) visit will occur 7 days after End of Treatment (EOT) (EOT + 7 days [±2 days]). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Day 3, EOT, TOC, LFU are the timepoints for the secondary endpoints.; Secondary end point(s): There are multiple secondary endpoints: • The proportion of patients in the m-MITT Population with overall treatment success at EOT and LFU; • The proportion of patients in the m-MITT and ME Populations with a microbiological outcome of Eradication at Day 3, EOT, TOC, and LFU; • The proportion of patients with a clinical outcome of Cure or Improvement (Day 3 only) in the m-MITT, Clinically Evaluable (CE), and ME Populations at Day 3, EOT, TOC, and LFU; • Per-pathogen clinical outcome of Cure and microbiological outcome of Eradication in the m-MITT and ME Populations at Day 3, EOT, TOC, and LFU; and • Subset of patients infected with extended-spectrum ß-lactamase producing pathogens with a clinical outcome of Cure and microbiological outcome of Eradication in the m-MITT and ME Populations at Day 3, EOT, TOC, and LFU. | — |
Countries
Argentina, Belarus, Bulgaria, Croatia, Estonia, Georgia, Hungary, Latvia, Lithuania, Mexico, Peru, Poland, Russian Federation, Serbia, Slovakia, South Africa, Spain, Ukraine, United States
Contacts
Public ContactHead of Regulatory Affairs
Allecra Therapeutics SAS
Outcome results
None listed