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

Phase 2

Completed

• Conditions: Community-Acquired Bacterial Pneumonia
• Interventions: Drug: CEM-101; Drug: Levofloxacin

• Registration Number: NCT01168713
• Lead Sponsor: Melinta Therapeutics, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2010-07-22
• Study First Submitted QC: 2010-07-22
• Study First Posted: 2010-07-23
• Study Start: 2010-08
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Disposition First Submitted: 2012-06-20
• Disposition First Submitted QC: 2012-06-29
• Disposition First Posted: 2012-07-03
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-01
• Last Update Posted: 2017-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

1. 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).
2. No prior systemic antibacterial therapy, unless failed other therapy.
3. Chest Xray shows new lobar or multilobar infiltrate(s) consistent with acute bacterial pneumonia.
4. PORT Risk Class II, III, or IV <=105
5. Ability to take oral medication.

Exclusion Criteria

1. Severe chronic obstructive pulmonary disease FEV1 <30%.
2. Hospitalization within 90 days or residence in a long-term-care facility within 30 days prior to the onset of symptoms
3. Chemotherapy or radiation therapy within the previous 3 months.
4. Significant hepatic, hematological, renal abnormalities.
5. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CEM-101	CEM-101	-
Levofloxacin	Levofloxacin	-

Primary Outcome Measures

Name	Time	Method
Clinical Success in the Intent to Treat (ITT) population at the Treatment of Cure (TOC) visit	5 to 10 days after the last dose of study drug	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
Clinical Success in the Clinically Evaluable (CE) population at the Treatment of Cure (TOC) Visit	5 to 10 days after the last dose of study drug	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

Secondary Outcome Measures

Name	Time	Method
By Patient Microbiological Response in the Microbiological Intent to Treat (microlITT) population at the Treatment of Cure (TOC) visit	5 to 10 days after the last dose of study drug	Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen
By Patient Microbiological Response in the Microbiological Intent to Treat (microlITT) population at the end of treatment (EOT)	5 days of study drug treatment	Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen.
By-patient Microbiological Response in the Microbiologically Evaluable (ME) populations at the end of treatment (EOT)	5 days of study drug treatment	Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen
By-patient Microbiological Response in the Microbiologically Evaluable (ME) populations at Treatment of Cure (TOC) visit	5 to 10 days after the last dose of study drug	Successful response is eradication, presumed eradication or combined eradication/presumed eradication of baseline pathogen
Clinical Response in the Intent to Treat (ITT) population at End of Treatment (EOT)	5 days of study drug treatment	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
Clinical Response in the microbiological intent to treat (microlITT) population at the end of treatment (EOT)	5 days of study drug treatment	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
Clinical Response in the clinically evaluable (CE) population at the end of treatment (EOT)	5 days of study drug treatment	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
Clinical REsponse in the Microbiologically Evaluable (ME) population at the end of treatment (EOT)	5 days of study drug treatment	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
Early Clinical Response in the intent to treat (ITT) population at Day 3	3 days of study drug treatment	Clinical success is defined as being both clinically stable and showing clinical improvement based on the symptoms of community acquired bacterial pneumonia (CABP)
Percentage of patients at each visit who have 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)	Resolution of all baseline signs and symptoms in the clinically evaluable (CE) population
Percentage of patients at Day 3 who have resolution of cough, dyspnea, chest pain due to pneumonia and sputum production	3 days of study drug treatment	Resolution of cough, dyspnea, chest pain due to pneumonia and sputum production
Percentage of patients at the end of treatment (EOT) who have resolution of cough, dyspnea, chest pain due to pneumonia and sputum production	5 days of study drug treatment	resolution of cough, dyspnea, chest pain due to pneumonia and sputum production
Percentage of patients at Day 3 who are clinically stable	3 days of study drug treatment	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)
Percentage of patients at the end of treatment (EOT) who are clinically stable	5 days of study drug treatment	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)