Systemic InfectionsPhase 1NCT01893346
Safety and Tolerability of Ceftazidime-Avibactam for Pediatric Patients With Suspected or Confirmed Infections
A Phase 1 study testing CAZ-AVI in people with Systemic Infections, run by Pfizer at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months to 17 years
- Conditions the study is for
- Systemic Infections
- What is being tested?
- CAZ-AVI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 10 sitesUnited States
- Study dates
- Jul 2013to Oct 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Research Site
Akron, Ohio
Research Site
Cleveland, Ohio
Research Site
Houston, Texas
Research Site
Little Rock, Arkansas
Research Site
Louisville, Kentucky
Research Site
Morgantown, West Virginia
Research Site
Omaha, Nebraska
Research Site
Orange, California
Research Site
San Diego, California
Research Site
Toledo, Ohio
About this study
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
To assess the pharmacokinetics, safety and tolerability of a single dose of CAZ-AVI in children from 3 months of age to <18 years.
Read the 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.
- Conditions
- Systemic Infections
- Being tested
- CAZ-AVI
- Keywords
- Ceftazidime, Avibactam, Anti-Infectives
- Medical subject headings
- Toxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAZ-AVIDrug
Single IV dose of Ceftazidime and Avibactam. Dosage regimen will vary depending on cohort.
| Study group | Role | What they receive |
|---|---|---|
| CAZ-AVI | Experimental | This arm will include 4 cohorts. Patients will be stratified by age. Receives: Drug: CAZ-AVI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic InfectionsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Paul Newell, MBBS, MRCP, Study director, AstraZenecaJohn Bradley, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01893346
- Sponsor's protocol ID
- D4280C00014
- Status last verified
- Sep 2017
- First submitted
- 26 Jun 2013
- Last updated
- 6 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 34687548Bradley 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.
PubMed 27503642
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01893346
- Acronym / sponsor ID
- D4280C00014
- Conditions
- Systemic Infections
- Keywords
- Ceftazidime, Avibactam, Anti-Infectives
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Study start
- Jul 2013
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 9 Jul 2013 (estimated)
- Results
- Posted 27 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAZ-AVI | Experimental | Drug: CAZ-AVIThis arm will include 4 cohorts. Patients will be stratified by age. |
Who may qualify
- Ages
- 3 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAZ-AVISingle IV dose of Ceftazidime and Avibactam. Dosage regimen will vary depending on cohort. | Drug | CAZ-AVI |
Primary outcome
Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: AUC
Time frame: Day 1
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
Time frame: Day 1
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34687548Franzese 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.
- Derived from this study: PubMed 27503642Bradley 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Newell, MBBS, MRCP study director
AstraZeneca
John Bradley, MD principal investigator
University of California, San Diego
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAZ-AVI in people with Systemic Infections, run by Pfizer at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic Parameters of Avibactam and Ceftazidime for Cohort 1 and 2: AUC (time frame: Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01893346, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2017.