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).

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.

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)