Safety and Tolerability of Ceftazidime-Avibactam for Pediatric Patients With Suspected or Confirmed Infections

Study Overview
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Brief Summary
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To assess the pharmacokinetics, safety and tolerability of a single dose of CAZ-AVI in children from 3 months of age to <18 years.

Detailed Description
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This is a phase I, open-label, single-dose study. The study aims to characterize the pharmacokinetics of CAZ-AVI and assess its safety and tolerability following a single IV dose given to hospitalized pediatric patients receiving systemic antibiotic therapy for suspected or confirmed infection. This study will include 4 cohorts, each consisting of at least 8 evaluable pediatric patients, aged ≥3 months to <18 years, who are hospitalized with infections.

Official Title
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A Phase I Study to Assess the Pharmacokinetics, Safety and Tolerability of a Single Dose of Ceftazidime-Avibactam (CAZ-AVI) in Children From 3 Months of Age to <18 Years Who Are Receiving Systemic Antibiotic Therapy for Suspected or Confirmed Infection

Conditions
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Systemic Infections

Intervention / Treatment
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* Drug: CAZ-AVI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent will be obtained from parent(s) or other legally acceptable representative(s), and informed assent from patient (if age appropriate) will be obtained Male or female children ages ≥3 months to <18 years. Hospitalized, receiving systemic antibiotic therapy for the treatment of a suspected or confirmed infection, and expected to require hospitalization until after the end of treatment (EOT) evaluations are completed. If female and has reached menarche, or has reached Tanner stage 3 breast development (even if not having reached menarche), the patient is practicing appropriate birth control or is sexually abstinent. Likely to survive the current illness or hospitalization. Sufficient intravascular access (peripheral or central) to receive study drug. Exclusion Criteria: History of hypersensitivity reactions to carbapenems, cephalosporins, penicillin, other β-lactam antibiotics. If female, currently pregnant or breast feeding or has a positive serum β-human chorionic gonadotropin (β-hCG) pregnancy test. Receipt of a blood or blood component (e.g., red blood cells, fresh frozen plasma, platelets) transfusion during the 24-hour period before enrolment. BMI outside the range (below the 5th percentile or above the 85th percentile) for height, age, and weight except for children <2 years of age. Babies born prior to 37 weeks gestation (cohort 4 only).

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAZ-AVI<br>This arm will include 4 cohorts. Patients will be stratified by age. | Drug: CAZ-AVI<br>* Single IV dose of Ceftazidime and Avibactam. Dosage regimen will vary depending on cohort.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: AUC | Key PK parameters were prespecified to be calculated for cohorts 1 and 2. For cohorts 3 and 4 (where children were <6 years of age), sparse sampling scheme was used for PK samples to limit the volume of blood required. PK parameters cannot be derived from these sparse PK samples without population PK analysis. Thus the PK is not described here, but will be reported in a separate population PK report. | Day 1 | 
| Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: Cmax | Key PK parameters are shown for cohorts 1 and 2. For cohorts 3 and 4 (where children were <6 years of age), sparse sampling scheme was used for PK samples to limit the volume of blood required. PK parameters cannot be derived from these sparse PK samples without population PK analysis. Thus the PK is not described here, but will be reported in a separate population PK report. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ceftazidime, Avibactam, Anti-Infectives