Clinical trial NCT01893346: Safety and Tolerability of Ceftazidime-Avibactam for Pediatric Patients With Suspected or Confirmed Infections
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Infections
Keywords: Ceftazidime, Avibactam, Anti-Infectives
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2013-07-09
Enrollment: 35
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Male or female children ages ≥3 months to \<18 years.
3. 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.
4. 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.
5. Likely to survive the current illness or hospitalization.
6. Sufficient intravascular access (peripheral or central) to receive study drug.

Exclusion Criteria:

1. History of hypersensitivity reactions to carbapenems, cephalosporins, penicillin, other β-lactam antibiotics.
2. If female, currently pregnant or breast feeding or has a positive serum β-human chorionic gonadotropin (β-hCG) pregnancy test.
3. Receipt of a blood or blood component (e.g., red blood cells, fresh frozen plasma, platelets) transfusion during the 24-hour period before enrolment.
4. 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.
5. Babies born prior to 37 weeks gestation (cohort 4 only).

Primary outcomes:
measure: Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: AUC
timeFrame: Day 1
measure: Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: Cmax
timeFrame: Day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Toledo
country: United States
facility: Research Site
state: Ohio
city: Houston
country: United States
facility: Research Site
state: Texas
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
Study officials:
affiliation: AstraZeneca
name: Paul Newell, MBBS, MRCP
role: STUDY_DIRECTOR
affiliation: University of California, San Diego
name: John Bradley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Franzese RC, McFadyen L, Watson KJ, Riccobene T, Carrothers TJ, Vourvahis M, Chan PLS, Raber S, Bradley JS, Lovern M. Population Pharmacokinetic Modeling and Probability of Pharmacodynamic Target Attainment for Ceftazidime-Avibactam in Pediatric Patients Aged 3 Months and Older. Clin Pharmacol Ther. 2022 Mar;111(3):635-645. doi: 10.1002/cpt.2460. Epub 2021 Nov 22.
citation: Bradley JS, Armstrong J, Arrieta A, Bishai R, Das S, Delair S, Edeki T, Holmes WC, Li J, Moffett KS, Mukundan D, Perez N, Romero JR, Speicher D, Sullivan JE, Zhou D. Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6252-9. doi: 10.1128/AAC.00862-16. Print 2016 Oct.