Efficacy and Safety Study of Oral CEM-101 Compared to Oral Levofloxacin in Treatment of Patients With Community-Acquired Bacterial Pneumonia

Study Overview
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Brief Summary
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Study to evaluate the safety and efficacy of oral CEM-101 compared to oral Levofloxacin in the treatment of adults with moderate to moderately severe community-acquired bacterial pneumonia.

Detailed Description
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Community-acquired bacterial pneumonia is an acute infection of the pulmonary parenchyma with symptoms such as fever or hypothermia, chills, rigors, chest pain, and/or dyspnea. The widespread emergence of antibiotic resistant pathogens, including the macrolide-resistant Streptococcus pneumoniae, has resulted in a need for new and effective antibiotics that have activity again CABP pathogens. CEM-101 is the first fluoroketolide with excellent in vitro and in vivo activity against resistant S. pneumoniae and other key typical and atypical bacterial respiratory pathogens.

Official Title
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A Randomized, Double-Blind, Multi-Center Study to Evaluate the Efficacy and Safety of Oral CEM-101 Compared to Oral Levofloxacin in the Treatment of Patients With Community-Acquired Bacterial Pneumonia

Conditions
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Community-Acquired Bacterial Pneumonia

Intervention / Treatment
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* Drug: Levofloxacin
* Drug: CEM-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of community acquired bacterial pneumonia (e.g. cough with purulent sputum or change in character of sputum consistent with bacterial infection, dyspnea or tachypnea, chest pain due to pneumonia, fever, presence of rales and/or signs of consolidation). No prior systemic antibacterial therapy, unless failed other therapy. Chest Xray shows new lobar or multilobar infiltrate(s) consistent with acute bacterial pneumonia. PORT Risk Class II, III, or IV <=105 Ability to take oral medication. Exclusion Criteria: Severe chronic obstructive pulmonary disease FEV1 <30%. Hospitalization within 90 days or residence in a long-term-care facility within 30 days prior to the onset of symptoms Chemotherapy or radiation therapy within the previous 3 months. Significant hepatic, hematological, renal abnormalities. Any concomitant condition that, in the opinion of the Investigator, would preclude an evaluation of a response or make it unlikely that the contemplated course of therapy and follow-up could be completed (e.g. life expectancy <30 days).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levofloxacin<br> | Drug: Levofloxacin<br>* Levofloxacin once daily for 5 days: Levofloxacin 750 mg PO Days 1-5<br>* Other names: Levaquin;|
| Experimental: CEM-101<br> | Drug: CEM-101<br>* CEM-101 once daily for 5 days: CEM-101 800 mg PO Day 1 CEM-101 400 mg PO Days 2-5<br>* Other names: Solithromycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Success in the Intent to Treat (ITT) population at the Treatment of Cure (TOC) visit | Clinical Success defined as continued improvement or complete resolution of baseline signs and symptoms and if available, an improved/stable chest radiograph after the end of treatment | 5 to 10 days after the last dose of study drug | 
| Clinical Success in the Clinically Evaluable (CE) population at the Treatment of Cure (TOC) Visit | Clinical Success defined as continued improvement or complete resolution of baseline signs and symptoms and if available, an improved/stable chest radiograph after the end of treatment | 5 to 10 days after the last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| By Patient Microbiological Response in the Microbiological Intent to Treat (microlITT) population at the end of treatment (EOT) | Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen. | 5 days of study drug treatment | 
| By Patient Microbiological Response in the Microbiological Intent to Treat (microlITT) population at the Treatment of Cure (TOC) visit | Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen | 5 to 10 days after the last dose of study drug | 
| By-patient Microbiological Response in the Microbiologically Evaluable (ME) populations at the end of treatment (EOT) | Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen | 5 days of study drug treatment | 
| By-patient Microbiological Response in the Microbiologically Evaluable (ME) populations at Treatment of Cure (TOC) visit | Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen | 5 to 10 days after the last dose of study drug | 
| Clinical Response in the Intent to Treat (ITT) population at End of Treatment (EOT) | Clinical Success is defined as complete or near-complete resolution of the baseline signs and symptoms of community acquired bacterial pneumonia (CABP); no further study drug for treatment of CABP | 5 days of study drug treatment | 
| Clinical Response in the microbiological intent to treat (microlITT) population at the end of treatment (EOT) | Clinical Success is defined as complete or near-complete resolution of the baseline signs and symptoms of community acquired bacterial pneumonia (CABP); no further study drug for treatment of CABP | 5 days of study drug treatment | 
| Clinical Response in the clinically evaluable (CE) population at the end of treatment (EOT) | Clinical Success is defined as complete or near-complete resolution of the baseline signs and symptoms of community acquired bacterial pneumonia (CABP); no further study drug for treatment of CABP | 5 days of study drug treatment | 
| Clinical REsponse in the Microbiologically Evaluable (ME) population at the end of treatment (EOT) | Clinical Success is defined as complete or near-complete resolution of the baseline signs and symptoms of community acquired bacterial pneumonia (CABP); no further study drug for treatment of CABP | 5 days of study drug treatment | 
| Early Clinical Response in the intent to treat (ITT) population at Day 3 | Clinical success is defined as being both clinically stable and showing clinical improvement based on the symptoms of community acquired bacterial pneumonia (CABP) | 3 days of study drug treatment | 
| Percentage of patients at each visit who have resolution of all baseline signs and symptoms in the clinically evaluable (CE) population | Resolution of all baseline signs and symptoms in the clinically evaluable (CE) population | Day 3, Day 5 (end of treatment), and 5 to 10 days after the last dose of study drug (test of cure visit) | 
| Percentage of patients at Day 3 who have resolution of cough, dyspnea, chest pain due to pneumonia and sputum production | Resolution of cough, dyspnea, chest pain due to pneumonia and sputum production | 3 days of study drug treatment | 
| Percentage of patients at the end of treatment (EOT) who have resolution of cough, dyspnea, chest pain due to pneumonia and sputum production | resolution of cough, dyspnea, chest pain due to pneumonia and sputum production | 5 days of study drug treatment | 
| Percentage of patients at Day 3 who are clinically stable | clinical stability defined as: Temperature <=37.8°C Heart rate <=100 beats/min Systolic blood pressure ≥90 mm Hg Ability to maintain oral intake Normal mental status (oriented to person, place or time) | 3 days of study drug treatment | 
| Percentage of patients at the end of treatment (EOT) who are clinically stable | Clinically stable defined as: Temperature ≤37.8°C Heart rate ≤100 beats/min Systolic blood pressure ≥90 mm Hg Ability to maintain oral intake Normal mental status (oriented to person, place or time) | 5 days of study drug treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults with Community-Acquired Bacterial Pneumonia