Safety and Efficacy Study of Ceftaroline Versus a Comparator in Pediatric Subjects With Complicated Skin Infections

Study Overview
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Brief Summary
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This is a study of safety, effectiveness, blood levels and tolerance of Ceftaroline fosamil in children with skin infections 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 Acute Bacterial Skin and Skin Structure Infections (ABSSSI).

Official Title
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A Multicenter, Randomized, Observer-Blinded, Active-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Ceftaroline Versus Comparator in Pediatric Subjects With Acute Bacterial Skin and Skin Structure Infections

Conditions
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Infections, Pediatrics

Intervention / Treatment
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* Drug: Ceftaroline fosamil
* Drug: Vancomycin +/- Aztreonam or Cefazolin +/- Aztreonam
* Drug: Cephalexin or Clindamycin or Linezolid


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 ABSSSI warranting initial hospitalization. Presence of ABSSSI with measurable margins of erythema, that includes deeper and/or extensive soft tissue involvement, or requires significant therapeutic surgical intervention Exclusion Criteria: Documented history of any hypersensitivity or allergic reaction to vancomycin, aztreonam, or any β-lactam antimicrobial Uncomplicated skin and soft tissue infections More than 24 hours of prior antimicrobial therapy ≤ 96 hours before randomization. Requirement for any concomitant systemic antimicrobial therapy History of seizures, excluding well-documented febrile seizure of childhood. Clinical signs or suspicion of meningitis

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 17 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 old: 12 mg/kg IV for subjects weighing ≤ 33 kg and 400 mg for subjects weighing > 33 kg will be infused over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour) Subjects < 6 months old: 8mg/kg infused over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour)<br>* Other names: PPI0903;Drug: Cephalexin or Clindamycin or Linezolid<br>* Possible oral switch on or after study day 4. Cephalexin: 25 mg/kg q6h PO or Clindamycin: 10 mg/kg q8h PO or Linezolid 600mg q12h (cohort 1) or 10 mg/kg q8h (cohorts 2,3 and 4) PO.<br>|
| Active Comparator: Comparators<br>Vancomycin +/- Aztreonam Cefazolin +/- Aztreonam | Drug: Vancomycin +/- Aztreonam or Cefazolin +/- Aztreonam<br>* Vancomycin 15mg/kg IV over 60 minutes (or a maximum of 10mg/min whichever is longer) +/- Aztreonam 30 mg/kg IV every 8 hours over 60 minutes (for infections involving gram negative pathogen suspected or confirmed) Cefazolin 75mg/kg IV divided every 8 hours over 60 minutes (for sites that do not empirically cover for MRSA) +/- Aztreonam 30 mg/kg IV every 8 hours over 60 minutes (for infections involving gram negative pathogen suspected or confirmed<br>Drug: Cephalexin or Clindamycin or Linezolid<br>* Possible oral switch on or after study day 4. Cephalexin: 25 mg/kg q6h PO or Clindamycin: 10 mg/kg q8h PO or Linezolid 600mg q12h (cohort 1) or 10 mg/kg q8h (cohorts 2,3 and 4) PO.<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 comparator in pediatric subjects ages 2 months to < 18 years with ABSSSI. | Evaluate the safety and tolerability of IV administered ceftaroline fosamil in children with skin infections. Summaries of AEs, SAEs, deaths, laboratory evaluations (hematology studies, comprehensive and metabolic panel), pain scales, vital signs, and physical examinations will be provided for each treatment group. | Between 26 and 50 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of ceftaroline versus comparator in pediatric subjects ages 2 months to < 18 years with ABSSSI. | The number and percentage of subjects in each treatment group classified as clinical cure in the Modified Intent to Treat (MITT) and Clinical Evaluable (CE) populations at Day 3, EOIV, EOT and TOC. | Between 1 and 5 days | 
| Evaluate the pharmacokinetics of ceftaroline versus comparator in pediatric subjects ages 2 months to < 18 years with ABSSSI. | Analyze concentrations of ceftaroline fosamil, ceftaroline, and M-1 in plasma, and if available, in cerebrospinal fluid (CSF; if collected as part of routine medical care) | Between 1 and 5 days | 

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