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

Phase 3
Completed
Conditions
Pneumonia
Interventions
Registration Number
NCT00336544
Lead Sponsor
Advanced Life Sciences, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
522
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 (HismanalĀ®) or pimozide (OrapĀ®)
  • 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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ClarithromycinClarithromycin-
CethromycinCethromycin-
Primary Outcome Measures
NameTimeMethod
Clinical Cures in the Intent to Treat PopulationTest of Cure Visit, defined as 14-22 days after the first dose of study

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.

Clinical Cures in the Per Protocol Clinically Evaluable PopulationTest of Cure Visit, defined as 14-22 days after the first dose of study

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.

Secondary Outcome Measures
NameTimeMethod
Bacteriologic Cures in the Intent to Treat PopulationTest of Cure Visit, defined as 14-22 days after the first dose of study

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).

Bacteriologic Cures in the Per Protocol Clinically Evaluable PopulationTest of Cure Visit, defined as 14-22 days after the first dose of study

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).

Trial Locations

Locations (13)

ISRAEL - Advanced Life Sciences

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Woodridge, Illinois, United States

PERU - Advanced Life Sciences

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Woodridge, Illinois, United States

POLAND - Advanced Life Sciences

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Woodridge, Illinois, United States

UKRAINE - Advanced Life Sciences

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Woodridge, Illinois, United States

ARGENTINA - Advanced Life Sciences

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Woodridge, Illinois, United States

ROMANIA - Advanced Life Sciences

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Woodridge, Illinois, United States

HUNGARY - Advanced Life Sciences

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Woodridge, Illinois, United States

BULGARIA - Advanced Life Sciences

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Woodridge, Illinois, United States

CHILE - Advanced Life Sciences

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Woodridge, Illinois, United States

CROATIA - Advanced Life Sciences

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Woodridge, Illinois, United States

ESTONIA - Advanced Life Sciences

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Woodridge, Illinois, United States

GERMANY - Advanced Life Sciences

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Woodridge, Illinois, United States

THE NETHERLANDS - Advanced Life Sciences

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Woodridge, Illinois, United States

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