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

NCT01893346 | Completed Phase 1 Results DMC

• 1 other identifier: D4280C00014
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 10

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.

Conditions

Systemic Infections

Keywords

Ceftazidime, Avibactam, Anti-Infectives

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

CAZ-AVI

EXPERIMENTAL

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

Drug: CAZ-AVI

Interventions

CAZ-AVI DRUG

Single IV dose of Ceftazidime and Avibactam. Dosage regimen will vary depending on cohort.

CAZ-AVI

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead
• Forest Laboratories: collaborator

Study Sites (10)

Research Site

Little Rock, Arkansas, United States

Location

Research Site

Orange, California, United States

Location

Research Site

San Diego, California, United States

Location

Research Site

Louisville, Kentucky, United States

Location

Research Site

Omaha, Nebraska, United States

Location

Research Site

Akron, Ohio, United States

Location

Research Site

Cleveland, Ohio, United States

Location

Research Site

Toledo, Ohio, United States

Location

Research Site

Houston, Texas, United States

Location

Research Site

Morgantown, West Virginia, United States

Location

Related Publications (2)

• 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.

  PMID: 34687548 DERIVED

• 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.

  PMID: 27503642 DERIVED

MeSH Terms

Conditions

Toxemia

Condition Hierarchy (Ancestors)

Infections

Results Point of Contact

• Title: Paul Newell, MBBS MRCP MFPM
• Organization: AstraZeneca Pharmaceuticals

paul.newell@astrazeneca.com

+44 1625 515727

Study Officials

• Paul Newell, MBBS, MRCP

  AstraZeneca

  STUDY DIRECTOR

• John Bradley, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2013
• First Posted: July 9, 2013
• Study Start: July 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: September 6, 2017
• Results First Posted: May 27, 2015

Record last verified: 2017-09

Locations

US (10)