Safety and Efficacy Study of Ceftaroline Versus a Comparator in Pediatric Subjects With Community Acquired Bacterial Pneumonia (CABP)

Study Overview
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Brief Summary
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This is a study of safety and effectiveness of ceftaroline fosamil in children with Community Acquired Bacterial Pneumonia receiving antibiotic therapy in the hospital.

Detailed Description
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To evaluate safety, effectiveness, pharmacokinetics and tolerance of ceftaroline fosamil in children who are initially hospitalized with Community Acquired Bacterial Pneumonia (CABP)

Official Title
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A Multicenter, Randomized, Observer-Blinded, Active-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Ceftaroline Versus Ceftriaxone in Pediatric Subjects With Community-acquired Bacterial Pneumonia Requiring Hospitalization

Conditions
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Infections, Community Acquired Pneumonia

Intervention / Treatment
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* Drug: Ceftaroline fosamil
* Drug: Ceftriaxone
* Drug: amoxicillin clavulanate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 2 months to < 18 years old. Presence of CABP requiring hospitalization and IV antibacterial therapy Exclusion Criteria: Documented history of any hypersensitivity of allergic reaction to any β-lactam antimicrobial. Confirmed or suspected infection with a pathogen known to be resistant to ceftriaxone. Confirmed or suspected respiratory tract infection attributed to sources other than CABP pathogens. Non-infectious causes of pulmonary infiltrates.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceftaroline fosamil<br> | Drug: Ceftaroline fosamil<br>* Treatment Group 1: Drug: Ceftaroline fosamil Children ≥ 6 months: IV ceftaroline fosamil 12 mg/kg for subjects weighing ≤ 33 kg or 400 mg for subjects weighing > 33 kg will be infused over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour) Children < 6 months: Ceftaroline fosamil 8 mg/kg over 60 (± 10) minutes q8h (± 1 hour)<br>* Other names: PPI0903;Drug: amoxicillin clavulanate<br>* Oral Switch for Treatment Groups 1 and 2: PO amoxicillin clavulanate 90 mg/kg/day divided q12h in subjects with infections due to susceptible organisms on or after Study Day 4 (a minimum of 7 IV doses required if randomized to ceftaroline.)<br>|
| Active Comparator: Ceftriaxone<br> | Drug: Ceftriaxone<br>* Treatment group 2: 75 mg/kg/day up to 4 g/day IV in equally divided doses, each infused over 30 (± 10) minutes q12hr (± 2 hours)<br>Drug: amoxicillin clavulanate<br>* Oral Switch for Treatment Groups 1 and 2: PO amoxicillin clavulanate 90 mg/kg/day divided q12h in subjects with infections due to susceptible organisms on or after Study Day 4 (a minimum of 7 IV doses required if randomized to ceftaroline.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety and tolerability of ceftaroline versus ceftriaxone in pediatric subjects age 2 months to <18 years with CABP requiring hospitalization | Evaluate the safety and tolerability of IV administered ceftaroline fosamil in children with CABP. Summaries of AEs, SAEs, deaths, laboratory evaluations (hematology studies, comprehensive and metabolic panel), vital signs. | Between 1 and 50 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of ceftaroline versus ceftriaxone in pediatric subjects ages 2 months to under 18 years with CABP. | Clinical response by subject and by baseline pathogen at Study Day 4 in the Modified Intent-to-Treat (MITT) and Microbiological modified Intent-to Treat (mMITT) Populations Clinical stability by subject and by baseline pathogen at Study Day 4 in the MITT and mMITT Populations Clinical outcome at EOIV, EOT, and TOC in the MITT and Clinically Evaluable (CE) Populations Clinical and microbiological outcomes by subject and by pathogen at TOC in the mMITT and Microbiologically Evaluable (ME) Populations Clinical relapse at LFU in the MITT Population Emergent infections in the mMITT Population | Between 4 and 50 days | 
| To evaluate the pharmacokinetics of ceftaroline in pediatric subjects ages 2 months to under 18 years. | Analyze concentrations of ceftaroline, ceftaroline fosamil (prodrug), and ceftaroline M-1 (inactive metabolite) in plasma, and, if available, in cerebrospinal fluid (CSF; if collected as part of standard of care). | Between 4 and 50 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infections, Pediatrics, Teflaro, cephalosporin