Evaluation of Ceftaroline Fosamil Versus a Comparator in Adult Subjects With Community-acquired Bacterial Pneumonia (CABP) With Risk for Methicillin-resistant Staphylococcus Aureus

NCT01645735 | Completed Phase 4 Results

• 1 other identifier: P903-25
• Study Type: interventional
• Target: 49
• Locations: 8 countries
• Sites: 31

Brief Summary

The purpose of this study is to determine whether ceftaroline is effective and safe for the treatment of patients with Community-acquired Bacterial Pneumonia (CABP) at risk for infection due to Methicillin-resistant Staphylococcus aureus (MRSA).

Conditions

Infections

Keywords

Infections; Teflaro; cephalosporin; Ceftaroline; antibiotics; pneumonia

Outcome Measures

Primary Outcomes (2)

• Clinical Response at Study Day 4 in the Modified Intent-to-Treat (MITT) Population

  Clinical response was defined as meeting all of the following criteria: * Symptom Improvement - Improvement in at least 2 and no worsening of any of the following symptoms compared to baseline: * Cough * Dyspnea * Sputum production * Chest pain * Clinical Stability (per Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines; Mandell et al, 2007): * Temperature ≤ 37.8°C * Heart rate ≤ 100 beats/min * Respiratory rate ≤ 24 breaths/min * Systolic blood pressure ≥ 90 mmHg * Oxygen saturation ≥ 90% * Confusion/disorientation absent

  Study Day 4

• Clinical Outcome at Test of Cure (TOC) in the MITT Population

  An assessment of clinical outcome was made by the Investigator at TOC. The clinical outcome categories were: Cure: Resolution of all acute signs and symptoms of CABP or improvement to such an extent that no further antimicrobial therapy was required Failure: Subjects who meet either of the following criteria: * Incomplete resolution or worsening of CABP signs and symptoms or development of new CABP signs or symptoms requiring alternative nonstudy antimicrobial therapy * Death in which CABP is contributory Indeterminate: Study data are not available for evaluation of efficacy for any reason, including: * Death in which CABP is clearly noncontributory * Lost to follow-up * Extenuating circumstances precluding classification as a cure or failure A favorable clinical outcome at Test-of Cure (TOC) was clinical cure.

  Test of Cure, an average of 3 weeks

Other Outcomes (2)

• Microbiological Outcomes by Baseline Pathogen at TOC in the Microbiological Modified Intent-to-Treat (mMITT) Population

  Test of Cure, an average of 3 weeks

• Safety Evaluation

  Baseline (Day 0) to Day 49

Study Arms (2)

Ceftaroline

EXPERIMENTAL

Ceftaroline fosamil 600 mg Intravenous (IV) administration over 60 minutes, every 8 hours (q8h); dosing to be adjusted for renal function; treatment duration 5 to 14 days

Drug: Ceftaroline fosamil

Ceftriaxone plus vancomycin

ACTIVE COMPARATOR

Ceftriaxone 2 g IV over 30 minutes once per day (q24h) plus vancomycin 15 mg/kg IV every 12 hours (q12h) initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days

Drug: Ceftriaxone plus vancomycin

Interventions

Ceftaroline fosamil DRUG

Ceftaroline fosamil 600 mg IV over 60 minutes q8h; treatment duration 5 to 14 days

Also known as: Teflaro, PPI-0903, TAK-599, TAK599, PPI0903 Teflaro

Ceftaroline

Ceftriaxone plus vancomycin DRUG

Ceftriaxone 2g IV over 30 minutes q24h plus vancomycin 15 mg/kg IV q12h initially and then dose adjusted based on trough concentrations; treatment duration 5 to 14 days

Ceftriaxone plus vancomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, ≥ 18 years old
• Presence of CABP requiring hospitalization
• Presence of CABP meeting the following criteria:
• I. confirmed pneumonia (new or progressive pulmonary) II. Acute illness (≤ 7 days' duration) with at least 3 clinical signs or symptoms consistent with a lower respiratory tract infection
• MRSA Risk Factors
• MRSA-positive blood culture or respiratory specimen or a risk factor for MRSA such as a history of colonization with MRSA

You may not qualify if:

• History of any hypersensitivity or allergic reaction to any β-lactam antimicrobial
• Suspected or microbiologically-documented infection with a pathogen known to be resistant to any of the study drugs
• Non-infectious causes of pulmonary infiltrates (eg, pulmonary embolism, chemical pneumonitis from aspiration, hypersensitivity pneumonia, congestive heart failure)
• More than 24 hours of potentially effective systemic antibacterial therapy for CABP within 96 hours before randomization
• End-stage renal disease \[Creatinine Clearance (CrCl) \< 15\], including hemodialysis
• Evidence of significant hepatic, hematological, or immunocompromising condition

Sponsors & Collaborators

• Forest Laboratories: lead
• AstraZeneca: collaborator

Study Sites (31)

Investigational Site

Phoenix, Arizona, 85008, United States

Location

Investigational Site

Sylmar, California, 91342, United States

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DeLand, Florida, 32720, United States

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Chicago, Illinois, 60611, United States

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Kansas City, Kansas, 66012, United States

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Royal Oak, Michigan, 48073, United States

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Minneapolis, Minnesota, 55145, United States

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St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68131, United States

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Laconia, New Hampshire, 03246, United States

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Columbus, Ohio, 43215, United States

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Lima, Ohio, 45801, United States

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Oklahoma City, Oklahoma, 73104, United States

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Tbilisi, 0144, Georgia

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Mátraháza, 3233, Hungary

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Lodz, 90-153, Poland

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Lublin, 20-954, Poland

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Wilkowice-Bystra, 43-365, Poland

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Craiova, Dolj, 200515, Romania

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Bucharest, 030303, Romania

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Iași, 700115, Romania

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Moscow, 109240, Russia

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Saint Petersburg, 196247, Russia

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Yaroslavl, 150003, Russia

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Alicante, 03010, Spain

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Barcelona, 08304, Spain

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Dnipropetrovsk, 49059, Ukraine

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Ivano-Frankivsik, 76018, Ukraine

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Kharkiv, 61115, Ukraine

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Kyiv, 03680, Ukraine

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Investigational Site

Zaporizhzhya, 69035, Ukraine

Location

Related Links

• Related Info

MeSH Terms

Conditions

Infections; Pneumonia

Interventions

Ceftaroline; Ceftriaxone; Vancomycin

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cefotaxime; Cephacetrile; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Small number of subjects enrolled

Results Point of Contact

• Title: Medical Monitor
• Organization: Cerexa, Inc

(510) 285-9200

Study Officials

• Medical Monitor

  Forest Laboratories Inc, an affiliate of Allergan plc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2012
• First Posted: July 20, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 1, 2016
• Results First Posted: February 1, 2016

Record last verified: 2015-12

Locations

ES (2); US (13); RO (3); GE (1); PL (3); HU (1); UA (5); RU (3)