Adults Subjects with Community-Acquired Pneumonia MedDRA version: 9.1 Level: LLT Classification code 10010120 Term: Community acquired pneumonia
Conditions
Interventions
Product Name: Ceftaroline for Injection (Ceftaroline)
Product Code: USAN: Ceftaroline fosamil
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Ceftaroline fosamil
CAS Number:
Sponsors
Cerexa, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females 18 or more years of age 2. Community-acquired pneumonia 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 (=7 days’ duration) with at least three of the following clinical signs or symptoms consistent with a lower respiratory tract infection: • New or increased cough • Purulent sputum or change in sputum character • Auscultatory findings consistent with pneumonia (e.g. rales, egophony, findings of consolidation) • Dyspnea, tachypnea, or hypoxemia (O2 saturation 38.5ºC rectally or tympanically) or hypothermia (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. PORT score less than or equal to 70 (PORT Risk Class I, or II), PORT score greater than 130 (PORT Risk Class V), or requiring admission to an intensive care unit 2. CAP suitable for outpatient therapy with an oral antimicrobial agent. Confirmed or suspected respiratory tract infections attributable to sources other than community-acquired bacterial pathogens. 4. Non-infectious causes of pulmonary infiltrates (e.g. pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure) 5. Pleural empyema (not including non-purulent parapneumonic effusions) 6. Microbiologically-documented infection with a pathogen known to be resistant to ceftriaxone, or epidemiological or clinical context suggesting high likelihood of a ceftriaxone-resistant “typical” bacterial pathogen. 7. Infection with an atypical organism (M. pneumoniae, C. pneumoniae, Legionella spp.) is confirmed, or suspected based upon the epidemiological context. 8. Previous treatment with an antimicrobial for treatment of CAP within 96 hours leading up to randomization. EXCEPTIONS: subjects may be eligible despite prior antimicrobial therapy if they meet the following conditions: EITHER: A single dose of an oral or intravenous short-acting antibiotic for CAP (see Appendix 2 for a list of allowed and disallowed antibiotics) OR BOTH OF THE FOLLOWING: • Unequivocal clinical evidence of treatment failure (e.g. worsening signs and symptoms) following at least 48 hours of prior systemic antimicrobial therapy • Isolation of an organism resistant to the prior, systemic, antimicrobial therapy 9. Failure of ceftriaxone (or other third-generation cephalosporin) as therapy for this episode of CAP or prior isolation of an organism associated with this episode of CAP and resistant in vitro to ceftriaxone 10. History of any hypersensitivity or allergic reaction to any ß-lactam antimicrobial 11. History of any hypersensitivity or allergic reaction to clarithromycin or any macrolide/ ketolide 12. Inability to take oral clarithromycin 13. Requirement for concomitant therapy with any drug known to exhibit a contraindicated drug-drug interaction with clarithromycin; or labeled contraindication to use of clarithromycin 14. Past or current history of epilepsy or seizure disorder- EXCEPTION: well-documented febrile seizure of childhood 15. Requirement for concomitant antimicrobial or systemic antifungal therapy for any reason. EXCEPTIONS: topical antifungal or antimicrobial therapy, a single oral dose of any antifungal for treatment of vaginal candidiasis 16. Neoplastic lung disease, cystic fibrosis, progressively fatal disease, chronic neurological disorder preventing clearance of pulmonary secretions, or life expectancy of less than or equal to 3 months. 17. Probenecid administration within 3 days prior to initiation of the study treatment regimen or requirement for concomitant therapy with probenecid 18. Infections or conditions requiring concomitant systemic corticosteroids. EXCEPTION: the corticosteroid dose equivalent is less than 40 mg prednisone per day 19. Severely impaired renal function (CrCl = 30 mL/min) estimated by the Cockroft-Gault formula. 20. Evidence of significant hepatic, hematological, or immunologic disease. 21. Evidence of immediately life-threatening disease. 22. Residence in a nursing home or assisted living facility that provides 24-hour medical supervision (not including extended living facilities for ambulatory elderly persons)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the non-inferiority in the clinical cure rate for ceftaroline compared to that for ceftriaxone at the TOC visit in the CE and MITT Efficacy (MITTE) Populations in adult subjects with CAP.;Secondary Objective: • Evaluate the clinical response at the End-of-Therapy (EOT) • Evaluate the microbiological favorable outcome rate at the TOC visit • Evaluate the overall (clinical and radiographic) success rate at the TOC visit • Evaluate the clinical and microbiological response by pathogen at the TOC visit • Evaluate clinical response at the LFU visit • Evaluate microbiological re-infection/recurrence at the LFU visit • Evaluate safety;Primary end point(s): The Investigator will assess clinical outcome at the EOT and TOC visits, and radiographic outcomes at the TOC and LFU visits. The primary efficacy outcome measure is the per-subject clinical cure rate at the TOC visit in the CE and MITTE Populations. Subjects will be considered clinically cured at the TOC visit if they have total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy is necessary. Clinical improvement includes the absence of fever (temperature = 38°C oral or = 38.5°C rectally or tympanically) for at least 24 continuous hours, with temperature recorded twice daily, in addition to a substantial improvement in signs and symptoms of CAP. Substantial improvement includes a return to pre-CAP baseline levels for subjects with decreased pulmonary function (eg, subjects with chronic obstructive pulmonary disease). | — |
Countries
Austria, Bulgaria, Estonia, Germany, Hungary, Lithuania, Spain
Outcome results
None listed