A Study to Investigate PK, Safety, Tolerability of Cefepime-enmetazobactam in Pediatric Participants With cUTI

NCT05826990 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AT-202
• Study Type: interventional
• Target: 40
• Locations: 6 countries
• Sites: 6

Brief Summary

This phase 2 study is part of regulatory commitments in the United States (PSP) and Europe (PIP) to evaluate cefepime-enmetazobactam in paediatric participants with cUTI to support extension of the indication for cefepime-enmetazobactam to children with cUTI.

Conditions

Complicated Urinary Tract Infection

Outcome Measures

Primary Outcomes (12)

• Pharmacokinetics Cmax

  Maximum Plasma Concentration \[Cmax\] ; unit= mg/L

  Day 1 - Day 2

• Pharmacokinetics Tmax

  Time to reach Cmax (Tmax) ; unit= h

  Day 1 - Day 2

• Pharmacokinetics AUC0-tau

  Area under the plasma concentration time curve from time zero to the end of the dosing interval (AUC0-tau) ; unit= mg.h/L

  Day 1 - Day 2

• Pharmacokinetics AUC0-inf

  Area under the concentration time curve from time zero extrapolated to infinity (AUC0-inf) ; unit= mg.h/L

  Day 1 - Day 2

• Pharmacokinetics t1/2

  Elimination half-life (t1/2), apparent terminal elimination rate constant (λz) ; unit= h

  Day 1 - Day 2

• Pharmacokinetics CL & Vd

  Clearance (CL, volume of plasma cleared of the drug per unit time) ; unit= L, Volume of distribution (Vd) ; unit= L

  Day 1 - Day 2

• Pharmacokinetics Cmin

  Trough observed plasma concentration (Cmin) ; unit= mg/L

  Day 1 - Day 2

• Safety and Tolerability

  Patients with treatment emergent adverse events (AE); unit=percentage

  before 1st study intervention until EOT +28 Days (±5 Days)

• Safety and Tolerability

  Patients with drug related related treatment emergent (AE); unit=percentage

  before 1st study intervention until EOT +28 Days (±5 Days)

• Safety and Tolerability

  Patients with study intervention discontinuation due to AE; unit=percentage

  before 1st study intervention until EOT +28 Days (±5 Days)

• Safety and Tolerability

  Patients with serious adverse event (SAE); unit=percentage

  before 1st study intervention until EOT +28 Days (±5 Days)

• Safety and Tolerability

  Patients with drug related serious adverse event; unit=percentage

  before 1st study intervention until EOT +28 Days (±5 Days)

Secondary Outcomes (1)

• Efficacy assessment

  7 Days (±2 Days) after the end-of-therapy (EOT)

Study Arms (1)

cefepime and enmetazobactam unique study arm

EXPERIMENTAL

Each study participant will receive a two-hour intravenous administration of cefepime and enmetazobactam every 8 hours, as single drug in fixed dose combination (FDC) formulation at a ratio of 4 to 1.

Drug: cefepime and enmetazobactam combination

Interventions

cefepime and enmetazobactam combination DRUG

Cefepime and enmetazobactam fixed dose combination administered intravenously every 8 hours as single drug formulation

Also known as: cefepime-enmetazobactam

cefepime and enmetazobactam unique study arm

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant must be from birth to \<18 years of age. Participants up to 2 months must have been born at term or preterm with a gestational age ≥32 weeks.
• Written informed consent from parent(s) or other legally acceptable representative(s), and informed assent from participant (if age appropriate according to local regulations).
• If female and has reached menarche, or has reached Tanner stage 3 development, (even if not having reached menarche) the participant is authorized to participate in this clinical study if the following criteria are met:
• Participant has a negative urine and/or serum human chorionic gonadotropin test at screening visit. As serum tests may miss an early pregnancy, relevant menstrual history, and sexual history, including methods of contraception, should be considered
• Participant agrees to avoid conception from the time of screening until 7 days after receipt of study intervention and agrees not to attempt pregnancy from the time of screening until 7 days after EOT with study intervention, and participant agrees to follow guidelines received regarding continuation of abstinence, initiation of abstinence or about allowed contraception, and
• Participant reports sexual abstinence for the prior 3 months or reported the use of at least 1 of the acceptable methods of contraception, including an intrauterine device (with copper banded coil), levonorgestrel intrauterine system or regular medroxyprogesterone injections, or participant agrees to initiate sexual abstinence from the time of screening until 7 days after end of treatment (EOT) with study intervention.
• Participant has a clinically suspected and/or bacteriologically documented complicated urinary tract infection (cUTI) or acute pyelonephritis judged by the investigator to require the participant to be hospitalized for treatment with intravenous (i.v.) therapy.
• The causative pathogen is confirmed or suspected to be susceptible to cefepime-enmetazobactam.
• Participant has pyuria, defined as dipstick analysis positive for leukocyte esterase OR:
• If ≥1 year of age: White blood cell (WBC) count \>10 cells/µL in unspun urine or ≥10 cells/high power field in spun urine.
• If \<1 year of age: WBC count \>5 cells/µL in unspun urine or ≥5 cells/high power field in spun urine.
• 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

You may not qualify if:

• History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to cefepime, any cephalosporin, penicillins, β-lactamase inhibitors (e.g., tazobactam, sulbactam, or clavulanic acid), or other β-lactam agents.
• Previous enrolment in this study, or in another interventional study ≤30 days before i.v. administration of study intervention.
• Concurrent infection requiring systemic antibiotics in addition to the i.v. study intervention therapy at the time of first study intervention administration.
• 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. (Refer protocol ► Section 10.5, Appendix 5 for the list of allowed and disallowed antibiotics).
• 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.
• 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.
• Participant has suspected or known complete obstruction of any portion of the urinary tract, perinephric abscess, or ileal loops.
• Participant has trauma to the pelvis or urinary tract.
• Participant has undergone renal transplantation.
• 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).
• 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.
• At the time of first study intervention administration, known presence of a cUTI caused by pathogens resistant to Cefepime - enmetazobactam.
• Presence of any of the following clinically significant laboratory abnormalities:

Sponsors & Collaborators

• Allecra: lead
• Linical Co., Ltd.: collaborator

Study Sites (6)

Fakultní nemocnice Hradec Králové -Ústav klinické biochemie a diagnostiky

Hradec Králové, 500 05, Czechia

RECRUITING

Hopital des Enfants

Toulouse, France

NOT YET RECRUITING

Debreceni Egyetem Klinikai Központ Gyermekgyógyászati Klinika

Debrecen, Hungary

NOT YET RECRUITING

SZPZOZ im. Dzieci Warszawy w Dziekanowie Leśnym

Łomianki, Poland

RECRUITING

Národný ústav detských chorôb (NÚDCH)

Bratislava, Slovakia

NOT YET RECRUITING

Hospital Universitario La Paz

Madrid, Spain

NOT YET RECRUITING

MeSH Terms

Interventions

Cefepime; cefepime, enmetazobactam drug combination

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: April 24, 2023
• Study Start: September 11, 2023
• Primary Completion: September 30, 2025
• Study Completion: March 30, 2026
• Last Updated: January 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); CZ (1); PL (1); SL (1); FR (1); ES (1)