Study Comparing the Safety and Efficacy of Cethromycin to Clarithromycin for the Treatment of Community-Acquired Pneumonia (CAP)

A Double-Blinded, Randomized, Parallel Group, Multi-Center, Multi-National Comparative Study of the Safety and Efficacy of Cethromycin 300 mg QD to Clarithromycin (BIAXIN® Filmtab®) 250 mg BID for the Treatment of Community-Acquired Pneumonia in Adults

The purpose of this study is to compare the efficacy of cethromycin to clarithromycin for the treatment of mild to moderate community-acquired pneumonia (CAP).

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Clarithromycin; Drug: Cethromycin

Detailed Description

Lower respiratory tract infections remain one of the leading causes of death worldwide. Increasing rates of antibiotic resistance and newer, more pervasive pneumonia-causative pathogens contribute to this statistic. Currently available macrolide antibiotics for the treatment of community-acquired pneumonia are slowly losing effectiveness, resulting in the need to develop newer drugs to fight resistant infections. In this study, we compare the safety and efficacy of a common macrolide, clarithromycin, to a new ketolide, cethromycin.

• Study Type: Interventional
• Enrollment (Actual): 584
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Woodridge, Illinois, United States, 60517
      • CANADA - Advanced Life Sciences
    • Woodridge, Illinois, United States, 60517
      • SOUTH AFRICA - Advanced Life Sciences
    • Woodridge, Illinois, United States, 60517
      • USA - Advanced Life Sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ambulatory male or female, 18 years of age or older
• If female, non-lactating and at no risk or pregnancy (post-menopausal or must use adequate birth control)
• Positive Chest X-ray consistent with diagnosis of bacterial pneumonia
• Must be a suitable candidate for oral antibiotic therapy and must be able to swallow capsules intact
• Recent history of respiratory illness consistent with the clinical signs and symptoms of bacterial CAP
• Must be able to produce sputum

Exclusion Criteria:

• Prior hospitalization within previous 4 weeks
• Residence at a chronic care facility
• Active tuberculosis (or other mycobacterial infection, empyema, lung abscess, pulmonary embolism, pulmonary edema, cystic fibrosis, tumor (primary or metastatic) involving the lung, bronchial obstruction, a history of post-obstructive pneumonia (chronic obstructive pulmonary disease [COPD] is not exclusionary), known or suspected Pneumocystis carinii pneumonia
• Treatment with long-acting antimicrobial agents within the last 4 weeks, treatment with ceftriaxone, azithromycin or dirithromycin antibiotic within the last 7 days, or subjects who have received more than 24 hours of treatment with other antibiotics within 7 days prior to study drug administration
• Any infection which requires the use of a concomitant antimicrobial agent
• History of hypersensitivity or allergic reactions to macrolide, ketolide, quinolone, azalide or streptogramin antimicrobials
• Treatment with another investigational drug within the last 4 weeks
• Females who are pregnant or lactating
• Subjects with known significant renal or hepatic impairment or disease
• Subjects with a history of impaired renal function
• Evidence of uncontrolled clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological or endocrine disease, malignancy, or other abnormality (other than the disease being studied)
• Subjects who would require parenteral antimicrobial therapy for the treatment of pneumonia
• Any underlying disease or condition that would interfere with the completion of the study procedures and evaluations or absorption of the study drug
• Currently receiving or are likely to require any of the following medications during the period between 2 weeks prior to Evaluation 1 and within 24 hours after the last dose of study drug: astemizol (Hismanal®) or pimozide (Orap®)
• Currently receiving or are likely to require any of the following during the period from Evaluation 1 and within 24 hours after the last dose of study drug: theophylline or theophylline analogues (unless adequately monitored), carbamazepine, dexamethasone, phenobarbital, phenytoin, St. John's Wort, lamotrigine, troglitazone, warfarin and digitalis glycoside. Other barbiturates may be used with careful monitoring
• Subjects who are currently receiving or who are likely to require any of the following medications during the period between Evaluation 1 and 4: other systemic antibiotic therapy, rifampin or rifabutin
• Immunocompromised subjects, subjects receiving immunosuppressive agents, subjects with known human immunodeficiency virus (HIV) infections and history of acquired immune deficiency syndrome (AIDS) defining conditions or CD4+ T-lymphocyte count <200.
• Subject with known or suspected central nervous system (CNS) disorder that predisposes them to seizures/lower seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy)
• Previous treatment with cethromycin
• Subjects with signs of septic shock (e.g., mental confusion, severe hypoxemia, severe hypotension, any other condition requiring intensive care unit [ICU] admission)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clarithromycin	Drug: Clarithromycin; Clarithromycin 250 mg twice per day (BID) for 7 days, administered orally; Other Names: Biaxin; Klacid; Klaracid
Experimental: Cethromycin	Drug: Cethromycin; Cethromycin 300 mg once per day (QD) for 7 days, administered orally; Other Names: Restanza; ABT-773

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cures in the Intent to Treat Population	Investigators evaluated subjects for a clinical response of cure, failure, or indeterminate. Cure: Improvement or return to preinfection state or lack of progression of all pulmonary infiltrates, and resolution of all signs/symptoms present at enrollment. Failure: Persistence or worsening of signs/symptoms, the need for additional antibiotic, new pulmonary infection, progression of the chest radiograph, or death due to pneumonia. Indeterminate: Evaluation was not possible (lost to follow up, adverse event, major protocol violation). Indeterminates default to failure for analysis.	Test of Cure Visit, defined as 14-22 days after the first dose of study drug.
Clinical Cures in the Per Protocol Clinically Evaluable Population	Investigators evaluated subjects for a clinical response of cure, failure, or indeterminate. Cure: Improvement or return to preinfection state or lack of progression of all pulmonary infiltrates, and resolution of all signs/symptoms present at enrollment. Failure: Persistence or worsening of signs/symptoms, the need for additional antibiotic, new pulmonary infection, progression of the chest radiograph, or death due to pneumonia. Indeterminate: Evaluation was not possible (lost to follow up, adverse event, major protocol violation). Indeterminates default to failure for analysis.	Test of Cure Visit, defined as 14-22 days after the first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteriologic Cures in the Intent to Treat Population	All bacteriologically evaluable subjects (ie., the subject had at least one, protocol-defined evaluable pathogen) who demonstrated eradication of all evaluable pathogens (S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, L. pneumophila).	Test of Cure Visit, defined as 14-22 days after the first dose of study drug.
Bacteriologic Cures in the Per Protocol Clinically Evaluable Population	All bacteriologically evaluable subjects (ie., the subject had at least one, protocol-defined evaluable pathogen) who demonstrated eradication of all evaluable pathogens (S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, L. pneumophila).	Test of Cure Visit, defined as 14-22 days after the first dose of study drug.

Collaborators and Investigators

• Sponsor: Advanced Life Sciences, Inc.
• Investigators: Study Director: David A. Eiznhamer, PhD, Advanced Life Sciences

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: June 9, 2006
• First Submitted That Met QC Criteria: June 9, 2006
• First Posted (Estimate): June 13, 2006

Study Record Updates

• Last Update Posted (Estimate): February 26, 2010
• Last Update Submitted That Met QC Criteria: January 29, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Infection; Pneumonia; Advanced; Lung; Pulmonary; Clarithromycin; Respiratory; Infectious; Life; Sciences; Cethromycin; Restanza; Biaxin
• 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; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Clarithromycin; Cethromycin
• Other Study ID Numbers: CL05-001