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

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

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.

Study Overview

• Status: Completed
• Conditions: Community-Acquired Bacterial Pneumonia
• Intervention / Treatment: Drug: Levofloxacin; Drug: CEM-101

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 Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N2T9
  • Ontario
    • Hamilton, Ontario, Canada, L8N3Z5
    • Hamilton, Ontario, Canada, L8N4A6
    • Hamilton, Ontario, Canada, L8V1C3
    • Ottawa, Ontario, Canada, K1Y 4E9
    • Toronto, Ontario, Canada, M9W 4L6
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H-5H6
    • Sherbrooke, Quebec, Canada, J1H5N4
    • St. Jerome, Quebec, Canada, J7Z5T3
    • Trios-Rivieres, Quebec, Canada, G8Z3R9
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
  • Arizona
    • Flagstaff, Arizona, United States, 86001
  • California
    • Bell Gardens, California, United States, 90201
    • Chula Vista, California, United States, 91911
    • LeMesa, California, United States, 91942
    • Los Angeles, California, United States, 90015
    • Montclaire, California, United States, 91763
    • Norwalk, California, United States, 90650
    • Oceanside, California, United States, 92056
    • Oxnard, California, United States, 93030
    • Pasadena, California, United States, 91105
    • Torrence, California, United States, 90501
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • Debary, Florida, United States, 32713
    • Gainesville, Florida, United States, 32605
    • Hialeah, Florida, United States, 33012
    • Kissimmee, Florida, United States, 34741
    • Orlando, Florida, United States, 32837
  • Georgia
    • Blue Ridge, Georgia, United States, 30513
    • Columbus, Georgia, United States, 31904
    • Savannah, Georgia, United States, 31406
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Illinois
    • Morton, Illinois, United States, 61550
  • Iowa
    • Dubuque, Iowa, United States, 52001
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
    • New Bedford, Massachusetts, United States, 02740
  • Michigan
    • Detroit, Michigan, United States, 48202
    • Traverse City, Michigan, United States, 49684
  • Montana
    • Butte, Montana, United States, 59701
  • Nevada
    • Las Vegas, Nevada, United States, 89109
  • Ohio
    • Akron, Ohio, United States, 44304
    • Carlisle, Ohio, United States, 45005
  • Oregon
    • Eugene, Oregon, United States, 97404
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
  • South Carolina
    • Simpsonville, South Carolina, United States, 29681
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
  • Tennessee
    • Franklin, Tennessee, United States, 37067
  • Texas
    • Corsicana, Texas, United States, 75110
    • Houston, Texas, United States, 77093
    • Houston, Texas, United States, 77002
    • San Antonio, Texas, United States, 78238
  • Utah
    • Draper, Utah, United States, 84020
    • Magna, Utah, United States, 84044
    • Salt Lake City, Utah, United States, 84121

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:

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Levofloxacin	Drug: Levofloxacin; Levofloxacin once daily for 5 days: Levofloxacin 750 mg PO Days 1-5; Other Names: Levaquin
EXPERIMENTAL: CEM-101	Drug: CEM-101; CEM-101 once daily for 5 days: CEM-101 800 mg PO Day 1 CEM-101 400 mg PO Days 2-5; Other Names: Solithromycin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.

Publications and helpful links

General Publications

• Oldach D, Clark K, Schranz J, Das A, Craft JC, Scott D, Jamieson BD, Fernandes P. Randomized, double-blind, multicenter phase 2 study comparing the efficacy and safety of oral solithromycin (CEM-101) to those of oral levofloxacin in the treatment of patients with community-acquired bacterial pneumonia. Antimicrob Agents Chemother. 2013 Jun;57(6):2526-34. doi: 10.1128/AAC.00197-13. Epub 2013 Mar 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: July 22, 2010
• First Submitted That Met QC Criteria: July 22, 2010
• First Posted (ESTIMATE): July 23, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Adults with Community-Acquired Bacterial Pneumonia
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Pneumonia, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin; Solithromycin
• Other Study ID Numbers: CE01-200