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| Name | Class |
|---|---|
| Forest Laboratories | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAZ-AVI | Experimental | This arm will include 4 cohorts. Patients will be stratified by age. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAZ-AVI | Drug | Single IV dose of Ceftazidime and Avibactam. Dosage regimen will vary depending on cohort. |
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| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul Newell, MBBS, MRCP | AstraZeneca | Study Director |
| John Bradley, MD | University of California, San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Little Rock | Arkansas | United States | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34687548 | Derived | 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. | |
| 27503642 |
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Eligibility was determined by investigator, prior to enrollment. Patients were selected on the basis of the age requirements for the appropriate cohort and after obtaining written informed consent from the parent or legal guardian and assent from patients (as appropriate). Screening assessments were completed prior to study drug administration.
First patient enrolled: 26 July 2013 Last patient last visit: 09 October 2014
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | aged ≥12 to <18 years 2000 mg ceftazidime and 500 mg avibactam |
| FG001 | Cohort 2 | aged ≥6 to <12 years Weight <40 kg: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam Weight ≥40 kg: 2000 mg ceftazidime and 500 mg avibactam |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Orange |
| California |
| United States |
| Research Site | San Diego | California | United States |
| Research Site | Louisville | Kentucky | United States |
| Research Site | Omaha | Nebraska | United States |
| Research Site | Akron | Ohio | United States |
| Research Site | Cleveland | Ohio | United States |
| Research Site | Toledo | Ohio | United States |
| Research Site | Houston | Texas | United States |
| Research Site | Morgantown | West Virginia | United States |
| 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. |
| FG002 | Cohort 3 | aged ≥2 to <6 years Normal renal function or mild renal insufficiency: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam. Moderate renal insufficiency: 25 mg/kg ceftazidime and 6.25 mg/kg avibactam |
| FG003 | Cohort 4 | aged ≥3 months to <2 years Normal renal function or mild renal insufficiency: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam. Moderate renal insufficiency: 25 mg/kg ceftazidime and 6.25 mg/kg avibactam |
| Patients Who Received Full Infusion |
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| COMPLETED |
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| NOT COMPLETED |
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Baseline characteristics are shown for safety analysis set. The safety analysis set included all patients who received any amount of IV study dose of CAZ AVI.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | aged ≥12 to <18 years 2000 mg ceftazidime and 500 mg avibactam |
| BG001 | Cohort 2 | aged ≥6 to <12 years Weight <40 kg: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam Weight ≥40 kg: 2000 mg ceftazidime and 500 mg avibactam |
| BG002 | Cohort 3 | aged ≥2 to <6 years Normal renal function or mild renal insufficiency: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam. Moderate renal insufficiency: 25 mg/kg ceftazidime and 6.25 mg/kg avibactam |
| BG003 | Cohort 4 | aged ≥3 months to <2 years Normal renal function or mild renal insufficiency: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam. Moderate renal insufficiency: 25 mg/kg ceftazidime and 6.25 mg/kg avibactam |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 analysis set | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1 |
|
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| ||||||||||||||||||||||||||||||||||
| Primary | 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. | Pharmacokinetic analysis set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 |
|
From start of study dose infusion of CAZ AVI through the follow up period (Day 2 and Day 3)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | aged ≥12 to <18 years 2000 mg ceftazidime and 500 mg avibactam | 0 | 8 | 0 | 8 | ||
| EG001 | Cohort 2 | aged ≥6 to <12 years Weight <40 kg: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam Weight ≥40 kg: 2000 mg ceftazidime and 500 mg avibactam | 0 | 8 | 0 | 8 | ||
| EG002 | Cohort 3 | aged ≥2 to <6 years Normal renal function or mild renal insufficiency: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam. Moderate renal insufficiency: 25 mg/kg ceftazidime and 6.25 mg/kg avibactam | 0 | 8 | 4 | 8 | ||
| EG003 | Cohort 4 | aged ≥3 months to <2 years Normal renal function or mild renal insufficiency: 50 mg/kg ceftazidime and 12.5 mg/kg avibactam. Moderate renal insufficiency: 25 mg/kg ceftazidime and 6.25 mg/kg avibactam | 0 | 8 | 2 | 8 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
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| Blood triglycerides increased | Investigations | MedDRA 16.1 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
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| Procedural site reaction | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul Newell, MBBS MRCP MFPM | AstraZeneca Pharmaceuticals | +44 1625 515727 | paul.newell@astrazeneca.com |
| ID | Term |
|---|---|
| D014115 | Toxemia |
| ID | Term |
|---|---|
| D007239 | Infections |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| AUC(0-t) |
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| AUC(0-inf) |
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| Units | Counts |
|---|---|
| Participants |
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