Community-acquired bacterial pneumonia (CABP) MedDRA version: 14.1 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Ceftaroline fosamil
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: ceftaroline fosamil
CAS Number: 229016-73-3
Other descriptive name: PPI-0903, TAK-599, ceft
Sponsors
Cerexa, Inc. (subsidiary of Forest Laboratories)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects are required to meet the following iinclusion criteria: 1. Provides written informed consent, and has the willingness and ability to comply with all study procedures 2. Male or female, 18 years old 3. Presence of CABP warranting 3 days of initial hospitalization, a minimum of 3 days of intravenous (IV) antibacterial therapy, and a minimum of 5 days but no more than 14 days total of study therapy (IV and oral combined) 4. Presence of CABP meeting the following criteria: I. Radiographically-confirmed pneumonia (new or progressive pulmonary infiltrate[s] on chest radiograph [CXR] or chest computed tomography [CT] scan consistent with bacterial pneumonia) AND II. Acute illness ( 24 breaths/min), or hypoxemia (oxygen saturation 38?C) or hypothermia (temperature 10,000 white blood cells [WBC]/mm3 or 15% immature neutrophils (bands) regardless of total peripheral WBC count 5. At least 1 major or at least 2 minor risk factors for CABP due to MRSA, as defined by the following: Major MRSA Risk Factors . Gram-positive cocci in clusters identified on Gram stain of an adequate baseline sputum specimen (defined as 25 polymorphonuclear cells/low power field [LPF]) or other respiratory specimen (eg, pleural fluid, deep bronchial, deep tracheal) . MRSA-positive blood culture or respiratory specimen from current episode of CABP (including induced or expectorated sputum, pleural fluid, deep bronchial, or deep tracheal sample) by culture or diagnostic test Minor MRSA Risk Factors . Confirmed or suspected pleural empyema, pulmonary abscess, or necrotizing pneumonia, based on chest radiography characteristics (eg, CXR or CT scan) or diagnostic testing (eg, thoracentesis with pleural fluid analysis) . Severe CABP, defined as: A. Requirement for management in an intensive care unit OR B. Meets modified American Thoracic Society criteria for severe community-acquired pneumonia: - At least 1 major criterion: either a requirement for invasive mechanical ventilation or septic shock with the need for vasopressor therapy OR - At least 3 minor criteria: respiratory rate >= 30 breaths/min, PaO2/FiO2 ratio = 20 mg/dL, = 38 C plus cough or sore throat in the absence of a known cause other than influenza) or documented influenza infection (eg, by culture or diagnostic test) within 28 days of randomization 6. Subjects with healthcare-associate
Exclusion criteria
Exclusion criteria: Subjects must NOT meet any of the following exclusion criteria: 1. History of any hypersensitivity or allergic reaction to any ?-lactam antimicrobial, vancomycin, azithromycin, linezolid, or amoxicillin clavulanate 2. Diagnosed with CABP suitable for outpatient therapy with an oral antimicrobial agent, initial outpatient parenteral antimicrobial therapy (OPAT), or initial IV therapy in a home care setting 3. Suspected or microbiologically-documented infection with a pathogen known to be resistant to any of the study drugs (eg, Pseudomonas aeruginosa, extended-spectrum ?-lactamase [ESBL]-producing gram-negative rods) 4. Confirmed or suspected respiratory tract infection attributable to sources other than community-acquired bacterial pathogens (eg, ventilator-associated pneumonia, hospital-acquired pneumonia, visible/gross aspiration pneumonia, suspected viral, fungal, or mycobacterial infection of the lung [eg, cavitation due to tuberculosis]) 5. Non-infectious causes of pulmonary infiltrates (eg, pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure) 6. Positive Legionella pneumophila urinary antigen test 7. More than 24 hours of any potentially effective systemic antibacterial therapy for CABP within 96 hours before randomization. Exception: Unequivocal clinical evidence of treatment failure (eg, worsening signs and symptoms) following at least 48 hours of prior systemic antimicrobial therapy (not including failure to any of the study drugs), PLUS documented isolation of MRSA from blood or respiratory culture from current episode of CABP that is resistant to the prior systemic antimicrobial therapy. 8. Requirement for any potentially effective concomitant systemic antibacterial therapy 9. Requirement for high-dose (eg, equivalent to > 40 mg of prednisone per day) or prolonged (ie, > 14 days) systemic corticosteroid therapy 10. Past or current history of epilepsy or seizure disorder. Exception: well-documented febrile seizure of childhood. 11. End-stage renal disease (creatinine clearance 10 times the upper limit of normal (× ULN) or total bilirubin > 3 × ULN ? Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy ? Neutropenia defined as < 500 neutrophils/mm3 ? Thrombocytopenia defined as < 60,000 platelets/mm3 ? If human immunodeficiency virus (HIV)-positive, has either a CD4 count of ? 200 cells/mm3 at the last measurement or current diagnosis of another AIDS-defining illness 13. Participation in any study involving administration of an investigational agent or device within 30 days before randomization into this study or previously participated in the current study or in another study of ceftaroline fosamil (in which an active agent was taken or received) 14. Unable or unwilling to adhere to the study-specified procedures and restrictions 15. Evidence of immediately life-threatening disease, including, but not limited to, neoplastic lung disease, cystic fibrosis, acute heart failure, acute coronary syndrome, unstable arrhythmias, acute cerebrovascular events, chronic neurological disorder preventing clearance of pulmonary secretions, or life expectancy of 3 months or less 16. Any condition that would make
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Not applicable;Main Objective: ? Evaluate the efficacy of ceftaroline and azithromycin versus ceftriaxone and azithromycin plus vancomycin in adult subjects with community-acquired bacterial pneumonia (CABP) at risk for infection due to methicillin-resistant taphylococcus aureus (MRSA) ? Evaluate the safety of ceftaroline and azithromycin versus ceftriaxone and azithromycin plus vancomycin in adult subjects with CABP at risk for infection due to MRSA ? Evaluate the pharmacokinetics of ceftaroline in adult subjects with CABP at risk for infection due to MRSA;Primary end point(s): The primary endpoints for this study are efficacy, safety and pharmacokinetics of ceftaroline fosamil versus ceftriaxone plus vancomycin in adult subjects with CABP at risk for infection due to MRSA. Efficacy ? Symptom improvement at Study Day 4 in the Modified Intent-to-Treat (MITT) and Microbiological Modified Intent-to-Treat (mMITT) Populations ? Clinical stability at Study Day 4 in the MITT and mMITT Populations ? Clinical success (both symptom improvement and clinical stability) at Study Day 4 in the MITT and mMITT Populations ? Symptom improvement, clinical stability, and clinical success at Study Day 4 by baseline pathogen in the mMITT Population ? Clinical outcome at End-of-Intravenous Study Drug (EOIV), End-of-Therapy (EOT), and Test-of-Cure (TOC) in the MITT and Clinically Evaluable (CE) Populations ? Clinical and microbiological outcomes by subject and by baseline pathogen at TOC in the mMITT and Microbiologically Evaluable (ME) Populations ? Clinical relapse at Late Follow-up (LFU) in the MITT Population ? Emergent infections at EOT and TOC in the MITT and mMITT Populations ? 30-day all-cause mortality in the MITT Population Safety ? Adverse events (AEs), serious adverse events (SAEs), deaths, and discontinuations due to AEs ? Vital signs, hematology parameters, and chemistry parameters Pharmacokinetic Plasma concentrations of ceftaroline, ceftaroline f | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Georgia, Hungary, Poland, Romania, Russian Federation, Spain, Ukraine, United States
Contacts
Public ContactExecutive Director, Reg Affairs
Cerexa, Inc. (subisidiary of Forest Laboratories)
Outcome results
None listed