Safety and Efficacy Study of Ceftaroline Versus a Comparator in Pediatric Subjects With Complicated Community Acquired 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 Complicated Community-acquired Pneumonia receiving antibiotic therapy in the hospital.

Detailed Description
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To evaluate safety, effectiveness, pharmacokinetics and tolerance of ceftaroline fosamil in pediatric subjects ages 2 months to < 18 years who are initially hospitalized with Complicated Community Acquired Bacterial Pneumonia (CABP) at high risk of infection due to methicillin-resistant Staphylococcus aureus (MRSA)

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 Plus Vancomycin in Pediatric Subjects With Complicated Community-acquired Bacterial Pneumonia (CABP)

Conditions
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Infections, Pneumonia

Intervention / Treatment
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* Drug: Ceftaroline fosamil
* Drug: IV Ceftriaxone and Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of CABP warranting 3 days of initial hospitalization Confirmed presence of indicators of complicated CABP Exclusion Criteria: Hypersensitivity or allergic reaction to vancomycin or any β-lactam antimicrobial Confirmed or suspected infection with a pathogen known to be resistant to IV study drugs or known infection at baseline with a sole atypical organism Confirmed or suspected respiratory tract infection attributable to sources other than community acquired bacterial pneumonia 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>* Subjects ≥ 6 months: IV ceftaroline fosamil 15 mg/kg (or 600 mg if > 40 kg) infused over 120 (± 10) minutes q8h (± 1 hour) Subjects < 6 months: IV ceftaroline fosamil 10 mg/kg infused over 120 (± 10) minutes q8h (± 1 hour) Optional Oral Switch: PO amoxicillin clavulanate 45 to 90 mg/kg/day divided q12h PO clindamycin 13 mg/kg/dose PO linezolid 600 mg q12h (Cohort 1) or 10 mg/kg q8h<br>* Other names: PPI0903;|
| Active Comparator: IV Ceftriaxone and Vancomycin<br> | Drug: IV Ceftriaxone and Vancomycin<br>* IV ceftriaxone 75 mg/kg/day (up to 4 g/day) divided equally every 12 hours (q12h) (± 2 hours) infused over 30 (± 10) minutes AND IV vancomycin 15 mg/kg every 6 hours (q6h) (± 1 hour) infused over at least 60 minutes. Optional Oral Switch: PO amoxicillin clavulanate 45 to 90 mg/kg/day divided q12h PO clindamycin 13 mg/kg/dose PO linezolid 600 mg q12h (Cohort 1) or 10 mg/kg q8h<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 plus vancomycin in pediatric subjects ages 2 months to < 18 years with complicated community-acquired bacterial pneumonia (CABP) | Evaluate the safety and tolerability of IV administered ceftaroline fosamil in children with complicated CABP. Summaries of patient AEs, SAEs, deaths, discontinuations due to AEs, laboratory evaluations (hematology studies, comprehensive and metabolic panel), and vital signs will be provided for each treatment group. | between 1 and 57 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of ceftaroline versus ceftriaxone plus vancomycin in pediatric subjects with complicated CABP at high risk of infection due to methicillin-resistant Staphylococcus aureus (MRSA). | Evaluate the efficacy of ceftaroline versus ceftriaxone plus vancomycin in pediatric subjects with complicated CABP at high risk of infection due to methicillin-resistant Staphylococcus aureus (MRSA) by assessing clinical stability of the subject at study day 4 and clinical outcome at End of IV, End of Treatment and Test of Cure. | between 4 and 57 days | 
| Evaluate the pharmacokinetics of ceftaroline in pediatric subjects with complicated CABP at high risk of infection due to methicillin-resistant Staphylococcus aureus (MRSA) | 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 57 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infections, Pediatrics, Teflaro, Ceftriaxone, cephalosporin, Vancomycin, Clindamycin, Amoxicillin Clavulanate, Linezolid, MRSA, pneumonia