A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH)

Condition(s) studied

Investigational drug(s) / intervention(s)

Part A: ATM-AVI Single Dose, Cohorts 1-4: Single intravenous infusion of aztreonam-avibactam over 3 hours to assess pharmacokinetics, safety, and toleration.

Part B: Multiple-dose ATM-AVI, Cohorts 1-4: Multiple intravenous infusions of aztreonam-avibactam over 3 hours, repeated every 6-8 hours up to 14 days to assess pharmacokinetics, safety, toleration, and efficacy.

Study summary

The purpose of this study is to learn about the safety and effects of ATM-AVI for the possible treatment of infections caused by a type of bacteria called gram-negative bacteria.

The study medicine is a combination of an antibiotic, aztreonam (ATM), and another medicine, avibactam (AVI), which is used to help stop bacteria from being resistant to antibiotics. Antibiotics are medicines that fights bacteria and infections.

The study will include newborns and infants up to 9 months of age who are admitted in the hospital.

The study is conducted in 2 parts: Part A and Part B.

In Part A, all participants will receive a single intravenous (injected directly into a vein) infusion of ATM-AVI. This is to study the safety and effects of a single amount.

In Part B, all participants will receive multiple intravenous infusions of ATM-AVI as treatment for a possible or confirmed infection with gram-negative bacteria.

Eligibility

Primary outcome measure(s)

• Maximum Predicted Plasma Concentration (Cmax) of ATM and AVI — Up to Day 15
  Cmax is the maximum plasma concentration of ATM and AVI as population pharmacokinetic (popPK) analysis predicts.
• Area under the Concentration-Time Curve (AUC) of ATM-AVI — Up to Day 15
  AUC is a measure of the plasma concentration of ATM and AVI overtime as popPK analysis predicts.
• Plasma Elimination Half-Life (t1/2) — Up to Day 15
  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 Day 15
  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.
• Plasma concentrations of ATM and AVI by nominal sampling time — Up to Day 15
  Plasma concentrations of ATM and AVI on Day 1 and at steady state (Day 2 or later) will be summarized by the nominal sampling time using descriptive statistics (eg number, mean, standard deviation).
• 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 of study drug — Baseline up to Day 50
  Proportion of Participants reporting AEs leading to discontinuation of study drug 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 — Baseline up to Day 50
  Proportion of Participants reporting liver injury and acute kidney injury 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 (26)

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