Safety and Efficacy Study of Oxazolidinone to Treat Pneumonia

A Phase 2, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of RX-1741 in the Treatment of Adult Patients With Mild to Moderate Severity of Community-Acquired Pneumonia (CAP)

The purpose of this study is to determine whether RX-1741, an oxazolidinone antibiotic, is safe and effective in the treatment of mild to moderate community acquired pneumonia (CAP).

Study Overview

• Status: Completed
• Conditions: Community-Acquired Pneumonia (CAP)
• Intervention / Treatment: Drug: Radezolid; Drug: Radezolid; Drug: Radezolid

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Burnaby, British Columbia, Canada
      • Ronald Collette, MD
    • Kelowna, British Columbia, Canada
      • The Medical Arts Health Research Group
    • North Vancouver, British Columbia, Canada
      • Westview Research
    • Penticton, British Columbia, Canada
      • The Medical Arts Health Research Group
  • New Brunswick
    • Bathurst, New Brunswick, Canada
      • Maritime Research Center
  • Ontario
    • Hawkesbury, Ontario, Canada
      • Source Unique Research
    • London, Ontario, Canada
      • Gordon Schacter, MD
    • London, Ontario, Canada
      • London East Medical Centre
    • Newmarket, Ontario, Canada
      • SKDS Research Inc.
    • Ottawa, Ontario, Canada
      • University of Ottawa Health Services
    • Sarnia, Ontario, Canada
      • London Road Diagnostic Clinic and Medical Centre
  • Prince Edward Island
    • Montague, Prince Edward Island, Canada
      • Kings County Medical Centre
  • Quebec
    • Drummondville, Quebec, Canada
      • Rhodin Recherche Clinique
    • Montreal, Quebec, Canada
      • Centre Medical Acadie
• Russian Federation
  • Moscow, Russian Federation
    • Moscow Regional Scientific Research Clinical Institute named after M.F. Vladimirsky
  • Moscow, Russian Federation
    • Moscow State Medico-Stomatological University
  • Moscow, Russian Federation
    • State Healthcare Institution "City Clinical Hospital # 29"
  • Moscow, Russian Federation
    • State Healthcare Institution Moscow
  • St. Petersburg, Russian Federation
    • City Hospital # 31
  • St. Petersburg, Russian Federation
    • St. Petersburg City Hospital # 26
  • St. Petersburg, Russian Federation
    • St. Petersburg Pavlov State Medical University
  • St. Petersburg, Russian Federation
    • St. Petersburg Scientific-Research Institute of Pulmonology at State Medical University named after Academician I.P. Pavlov
• United States
  • California
    • San Diego, California, United States
      • eStudySite
    • Sylmar, California, United States
      • Olive View- UCLA Center, Dept. Emergency Medicine
  • Michigan
    • Detroit, Michigan, United States
      • Wayne State University School of Medicine/Detroit Receiving Hospital
    • Keego Harbor, Michigan, United States
      • Arnold Markowitz, MD
  • Montana
    • Butte, Montana, United States
      • Mercury Street Medical Group, LLC
  • New Jersey
    • Belvidere, New Jersey, United States
      • Dr. John Bernard
    • Cherry Hill, New Jersey, United States
      • University of Medicine & Dentistry of New Jersey, School of Osteopathic Medicine (UMDNJ-SOM)
  • Pennsylvania
    • Warminster, Pennsylvania, United States
      • Warminster Medical Associates, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with mild to moderate CAP.
• Adult men and women ≥18 years.
• Females must be post-menopausal for at least 1 year or surgically sterile (hysterectomy or tubal ligation).
• Sexually active males must use a barrier method of birth control during and for 30 days after the study. Their female partner should also use an additional reliable method of contraception during and for 30 days after the study.
• The patient must present with an acute respiratory illness (≤7 days duration) with which history and physical examination is consistent with a diagnosis of CAP.

Patients requiring immediate study drug therapy before serology or culture results are known may be entered with a presumptive diagnosis of CAP based on:

A chest radiograph at baseline, which shows a new infiltrate(s) consistent with pneumonia as interpreted by the radiologist or the investigator and subsequently confirmed by the radiologist.

AND at least 2 of the following signs and symptoms:

New or increased cough. Purulent sputum or change in sputum character. Auscultatory findings consistent with pneumonia. New onset or progressive dyspnea or tachypnea. Fever >38ºC oral or >38.5ºC tympanic. White blood cell (WBC) count greater than 10,000 cells/mm3 or >15% immature neutrophils (bands), regardless of total peripheral WBC count, or less than 4,500 cells/mm3.

Patient must be able to swallow large capsules intact.

A written, voluntarily signed informed consent must be obtained from the patient prior to the initiation of any study-related procedures.

Exclusion Criteria:

• Hypersensitivity to linezolid.
• Patients are excluded if they have taken oral or parenteral antibiotics as follows:

long-acting penicillin within 28 days of enrollment azithromycin, ceftriaxone, or telithromycin within 14 days prior to enrollment any other antibiotics for >24 hours within 3 days of enrollment

• Require parenteral antibiotics for the treatment for CAP.
• Patient should not have been hospitalized or resided in a long-term facility for at least 14 days before the onset of symptoms.
• Evidence of other pulmonary disease that precluded evaluation of therapeutic response. Patients with known bronchial obstruction or a history of postobstructive pneumonia. (This does not exclude patients who have chronic obstructive pulmonary disease).
• Experienced a recent clinically significant coagulopathy.
• History of cystic fibrosis, active tuberculosis, meningitis, endocarditis, or osteomyelitis.
• Immunocompromised patients including, but not limited to patients with a CD4+ cell count of <350 cells/mm3 secondary to human immunodeficiency virus (HIV) infection, neutropenic patients with granulocytes <1000/mm3 or immunosuppression secondary to drugs such as corticosteroid therapy (>10 mg/day of prednisone or equivalent for at least the past 3 months), splenectomized patients or patients with known hyposplenia or asplenia.
• Patients who have severe liver disease.
• Treatment with an investigational drug within 4 weeks prior to study drug administration.
• Any underlying condition or disease state that would interfere with the completion of the study procedures and evaluation of the absorption of study drug.
• Patients with bronchiectasis and a history of recent respiratory infection caused by Pseudomonas aeruginosa.
• Any infection which requires the use of a concomitant antimicrobial agent, in addition to study drug.
• Patients taking serotonergic agents, selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Radezolid 300 mg	Drug: Radezolid; 300 mg/day, orally for 7-10 days; Other Names: RX-1741; Drug: Radezolid; 450 mg/day orally for 7-10 days; Other Names: RX-1741; Drug: Radezolid; 900 mg/day orally for 7-10 days; Other Names: RX-1741
Experimental: 2; Radezolid 450 mg	Drug: Radezolid; 300 mg/day, orally for 7-10 days; Other Names: RX-1741; Drug: Radezolid; 450 mg/day orally for 7-10 days; Other Names: RX-1741; Drug: Radezolid; 900 mg/day orally for 7-10 days; Other Names: RX-1741
Experimental: 3; Radezolid 450 mg BID	Drug: Radezolid; 300 mg/day, orally for 7-10 days; Other Names: RX-1741; Drug: Radezolid; 450 mg/day orally for 7-10 days; Other Names: RX-1741; Drug: Radezolid; 900 mg/day orally for 7-10 days; Other Names: RX-1741

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure in the Clinically Evaluable (CE) Population at Test of Cure (TOC)	Patients were considered cured if all systemic signs and symptoms of CAP present at screening were improved or resolved and no further antibiotic therapy was necessary. In addition, the follow-up chest X-ray was to be either stable or improved.	Study days 14-38

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Per Patient Microbiological Response of Eradicated in the Microbiologically Evaluable (ME) Population at Test of Cure (TOC)	The number of ME patients (defined as those CE patients with evidence of 1 or more of 7 key CAP pathogens: S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, and L. pneumophila) with a microbiologic response of eradicated, i.e. either documented eradication of the baseline pathogen(s), or presumed eradication in the setting of clinical cure with no material to culture.	Study Days 14-38

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 18, 2008
• First Submitted That Met QC Criteria: March 20, 2008
• First Posted (Estimate): March 21, 2008

Study Record Updates

• Last Update Posted (Estimate): May 12, 2016
• Last Update Submitted That Met QC Criteria: April 7, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Oxazolidinones; Radezolid
• Other Study ID Numbers: RX-1741-201