Study of 2 Medicines (Aztreonam and Avibactam) Compared to Best Available Therapy for Serious Gram-negative Infections

Condition(s) studied

Investigational drug(s) / intervention(s)

ATM-AVI: A drug specifically designed to treat resistant gam-negative bacterial infections

BAT: BAT will be selected by the investigator and administered iv as appropriate for the selected drug(s)

Study summary

The purpose of this study is to evaluate how Aztreonam (ATM) and Avibactam (AVI) are processed in pediatric participants. This study also aims to understand participant safety and effects in pediatric participants.

The study is seeking participants who are:

* 9 months to less than 18 years of age
* Hospitalized
* Suspected/known to have a gram-negative infection
* Receiving intravenous (iv, given directly into a vein) antibiotics
* Being treated for complicated infections of various body parts that includes the abdomen, urinary tract, blood stream, and lungs.
* Participants will receive either ATM-AVI or best available therapy (BAT).
* Both therapies will be given through a vein.
* Participants with complicated abdominal infections will also receive iv Metronidazole (MTZ). Patients with cIAI and Cockayne Syndrome are excluded due to a risk of severe hepatotoxicity with the use of MTZ. - Participants on ATM-AVI treatment who have anaerobic infections will also receive iv MTZ at the study doctor's discretion.
* The iv dose of ATM-AVI will be based on the participant's weight and kidney function.
* The study doctor will determine the iv dose of BAT.
* During the first 2 study days, participants on ATM-AVI therapy will have 5 blood draws in small quantities.
* Starting on day 4, the study doctor will decide if participants may be switched to oral therapy.
* Participants will receive a maximum of 14 days of ATM-AVI treatment.
* After discharge from the hospital, 1 study visit may be required.
* Depending on the participant's response, the study duration will be from 33 to 50 days.
* The investigator will contact participants by phone 28 to 35 days after the last study treatment to check participants health status.

Eligibility

Primary outcome measure(s)

• Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI — Up to 15 Days
  Cmax is the maximum plasma concentration of ATM and AVI as population pharmacokinetic (popPK) analysis predicts.
• Minimum Predicted Trough Plasma Concentration (Cmin) of ATM and AVI — Up to 15 Days
  Cmin is the minimum trough plasma concentration of ATM and AVI as popPK analysis predicts.
• Area under the Concentration-Time Curve (AUC) of ATM-AVI — Up to 15 Days
  AUC is a measure of the plasma concentration of ATM and AVI overtime as popPK analysis predicts.
• Plasma Decay Half-Life (t1/2) — Up to 15 Days
  Half-life is the time measured for the plasma concentration of ATM and AVI to decrease by one half as popPK analysis predicts.
• Apparent Clearance (CL) — Up to 15 Days
  ATM and AVI clearance is a quantitative measure of the rate at which ATM and AVI are removed from the blood (rate at which ATM and AVI are metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed.
• Proportion of Participants reporting Adverse Events (AE) — Baseline up to Day 50
  Proportion of participant AE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each AE the last assessment made prior to the first dose of study drug will be defined as the baseline.
• Proportion of Participants reporting Serious Adverse Events (SAE) — Baseline up to Day 50
  Proportion of participant SAE reports of vital signs, physical examinations, and clinical laboratory tests overall and by age cohort. For each SAE the last assessment made prior to the first dose of study drug will be defined as the baseline.
• Proportion of Participants reporting AEs leading to discontinuation — Baseline up to Day 50
  Proportion of Participants reporting AEs leading to discontinuation from baseline. For each discontinuation the last assessment made prior to the first dose of study drug will be defined as the baseline
• Proportion of Participants reporting AEs resulting in death — Baseline up to Day 50
  Proportion of Participants reporting AE resulting in death from baseline. For each death the last assessment made prior to the first dose of study drug will be defined as the baseline
• Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT) — Baseline up to Day 50
  Proportion of Participants reporting liver injury and acute kidney injury of ATM-AVI relative to Best Available Therapy (BAT) from baseline. For each report of liver and acute kidney injury the last assessment made prior to the first dose of study drug will be defined as the baseline

Trial sites (23)