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

Primary Purpose

Systemic Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CAZ-AVI
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Systemic Infections focused on measuring Ceftazidime, Avibactam, Anti-Infectives

Eligibility Criteria

3 Months - 17 Years (Child)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAZ-AVI

Arm Description

This arm will include 4 cohorts. Patients will be stratified by age.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
June 26, 2013
Last Updated
September 1, 2017
Sponsor
Pfizer
Collaborators
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01893346
Brief Title
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

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Forest Laboratories

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Infections
Keywords
Ceftazidime, Avibactam, Anti-Infectives

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CAZ-AVI
Arm Type
Experimental
Arm Description
This arm will include 4 cohorts. Patients will be stratified by age.
Intervention Type
Drug
Intervention Name(s)
CAZ-AVI
Intervention Description
Single IV dose of Ceftazidime and Avibactam. Dosage regimen will vary depending on cohort.
Primary Outcome Measure Information:
Title
Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: AUC
Description
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.
Time Frame
Day 1
Title
Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: Cmax
Description
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.
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Newell, MBBS, MRCP
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
John Bradley, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
Research Site
City
Orange
State/Province
California
Country
United States
Facility Name
Research Site
City
San Diego
State/Province
California
Country
United States
Facility Name
Research Site
City
Louisville
State/Province
Kentucky
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
Research Site
City
Akron
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Toledo
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Morgantown
State/Province
West Virginia
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34687548
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.
Results Reference
derived
PubMed Identifier
27503642
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.
Results Reference
derived

Learn more about this trial

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

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