E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hospitalized pediatric patients receiving systemic antibiotic therapy for suspected or confirmed infection. |
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E.1.1.1 | Medical condition in easily understood language |
hospitalized pediatric patients receiving systemic antibiotic therapy for suspected or confirmed infection. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021804 |
E.1.2 | Term | Infection bacterial |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Characterization of the pharmacokinetics of single-dose CAZ-AVI in a pediatric population |
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E.2.2 | Secondary objectives of the trial |
Assessment of the safety and tolerability of a single IV dose of CAZ-AVI given to hospitalized pediatric patients via Adverse Events, Vital Signs, Physical Examiniation, Laboratory Parameters and ECGs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.) Male or female children ages ≥3 months to <18 years 2.) 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 3.) 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 abstinant 4.) Likely to survive the current illness or hospitalization 5.) Sufficient intravascular access (peripheral or central) to receive study drug. |
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E.4 | Principal 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 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following PK parameters will be determined for ceftazidime and avibactam and will be listed and summarized: maximum plasma concentration (Cmax; μg/mL) following a single dose administration; time to Cmax (tmax; in hours) following a single-dose administration; area under the plasma concentration-time curve from zero to 8 hours after the end of infusion (AUC[0-8]), the time of the last quantifiable concentration (AUC[0-t]), extrapolated to infinity (AUC[0-∞]); time of last quantifiable plasma concentration (tlast; in hours) taken directly from the individual concentration-time curve; terminal plasma half-life (t½; in hours) estimated as (ln2)/λz; systemic plasma clearance (CL; L/hour) estimated as dose divided by AUC(0-∞); volume of distribution at the terminal phase (Vz; L) estimated by dividing the systemic clearance by λz; volume of distribution at steady state (Vss, L) estimated by multiplying the mean residence time (MRT) by the CL; and terminal elimination phase rate constant (λz). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Co-hort 1: Up to 22 hours post dose
Co-hort 2: Up to 13 hours post dose
Co-horts 3 and 4: Up to 6 hours post dose |
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E.5.2 | Secondary end point(s) |
Safety and tolerability will be assessed by Adverse Events reports and the results of vital sign measurements, physical examinations, clinical laboratory tests and ECGs. Tabulations and listings of data for vital signs, physical examinations, clinical laboratory tests, and ECGs will be presented. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From consent to 48 hours post dose |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |