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Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults With Community-acquired Bacterial Pneumonia (DEFINE-CABP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02679573
Recruitment Status : Completed
First Posted : February 10, 2016
Results First Posted : February 27, 2020
Last Update Posted : February 27, 2020
Sponsor:
Information provided by (Responsible Party):
Melinta Therapeutics, Inc.

Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of delafloxacin compared to moxifloxacin in the treatment of adult patients with community-acquired pneumonia.

Condition or disease Intervention/treatment Phase
Community Acquired Bacterial Pneumonia Drug: Delafloxacin Drug: Moxifloxacin Drug: Linezolid Phase 3

Detailed Description:
The purpose of this study is to determine if delafloxacin, an investigational drug, is safe and effective in the treatment of community-acquired bacterial pneumonia compared with moxifloxacin, or linezolid in the case of confirmed MRSA.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 860 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate the Safety and Efficacy of Intravenous to Oral Delafloxacin in Adult Subjects With Community-Acquired Bacterial Pneumonia
Actual Study Start Date : December 14, 2016
Actual Primary Completion Date : July 31, 2018
Actual Study Completion Date : August 7, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Delafloxacin
IV delafloxacin with potential to switch to oral delafloxacin
Drug: Delafloxacin
Antibacterial agent, 300 mg IV, Q12H for at least 6 doses with potential to switch to 450 mg oral tablet, Q12H for up to 20 doses total
Other Name: RX-3341

Active Comparator: Moxifloxacin/Linezolid
IV moxifloxacin with potential to switch to oral moxifloxacin, and potential to switch moxifloxacin to IV linezolid for confirmed MRSA
Drug: Moxifloxacin
Antibacterial Agent, 400 mg IV, Q24H for at least 3 doses with potential to switch to 400 mg oral over-encapsulated tablet, Q24H for up to 10 doses total
Other Name: Avelox

Drug: Linezolid
Antibacterial Agent, at local investigator discretion, subjects in the moxifloxacin arm with confirmed MRSA can switch to linezolid 600 mg IV Q12H for all remaining doses
Other Name: Zyvox




Primary Outcome Measures :
  1. Early Clinical Response [ Time Frame: 96 (+/- 24) hours after the first dose of study drug ]
    Early clinical response defined as improvement in at least 2 of the following symptoms (as assessed by the investigator): chest pain, frequency or severity of cough, amount and quality of productive sputum, and difficulty breathing, and no worsening of the other symptoms in the ITT population. Symptom severity evaluated by the investigator on a 4-point scale: Absent (0), Mild (1), Moderate (2), Severe (3). Improvement defined as at least a 1-point decrease from baseline.


Secondary Outcome Measures :
  1. Early Clinical Response Plus Improvement in Vital Signs and no Worsening of the 4 Symptoms [ Time Frame: 96 (+/- 24) hours after the first dose of study drug ]
    Early clinical response with the addition of improvement in vital signs and no worsening of the following 4 symptoms: chest pain, cough, productive sputum, and difficulty breathing in the ITT population. Symptom severity evaluated by the investigator on a 4-point scale: Absent (0), Mild (1), Moderate (2), Severe (3). Improvement defined as at least a 1-point decrease from baseline. Improvement in vital signs defined as a return to normal of any abnormal vital signs at baseline, and no worsening (ie, be abnormal) of any vital sign that was normal at baseline.

  2. Clinical Outcome at Test of Cure [ Time Frame: 5 to 10 days after the last dose of study drug ]
    Clinical outcome (Success, Failure, or Indeterminate/missing) based on the investigator's assessment of the patient's signs and symptoms of infection in the ITT population.

  3. Clinical Outcome at End of Treatment [ Time Frame: Up to 24 (+4) hours after the last dose of study drug ]
    Clinical outcome (Success, Failure, or Indeterminate/missing) based on the investigator's assessment of the patient's signs and symptoms of infection in the ITT population.

  4. Microbiologic Response [ Time Frame: 5 to 10 days after the last dose of study drug ]
    Microbiological response for subjects in the MITT set will be based on results of the baseline and follow-up cultures and susceptibility testing or serology.

  5. All-cause Mortality [ Time Frame: Day 28 (+/- 2 days) ]
    Time to all-cause Mortality was assessed on Day 28.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female 18 years of age or older
  2. Evidence of acute onset of CABP with 2 or more of the following symptoms (new or worsening)

    • Cough
    • Production of purulent sputum consistent with bacterial infection
    • Difficulty breathing
    • Chest pain due to pneumonia

    AND have at least 2 of the following findings:

    • Fever (oral temperature >38.0°C)
    • Hypothermia (oral temperature <35.0°C)
    • Tachycardia (heart rate >100 beats/min)
    • Tachypnea (respiratory rate >18 breaths/min)

    AND have at least 1 of the following findings:

    • Hypoxemia (oxygen saturation <90% or PaO2 < 60 mmHg) on room air or with subject's baseline (pre-CABP under study) supplemental oxygen
    • Clinical evidence of pulmonary consolidation and/or presence of pulmonary rales
    • An elevated white blood cell count (WBC) >10,000/mm3 or 15% immature neutrophils (bands), regardless of total peripheral WBC count or leukopenia with WBC <4500/mm^3
  3. Presence of lobar, multilobar, or patchy parenchymal infiltrate(s) consistent with acute bacterial pneumonia on a pulmonary imaging study within 48 hours before the first dose of study drug
  4. PORT risk class of II to V (PSI score >50)
  5. Must be a suitable candidate for possible IV to oral switch antibiotic therapy and must also be able to swallow large tablets/capsules intact without crushing

Exclusion Criteria:

  1. A medical history of significant hypersensitivity or allergic reaction to antibiotics of the quinolone or oxazolidinone class or study drug excipients according to the investigator
  2. Any infection expected to require other systemic antibiotics in addition to study drug
  3. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless 1 of the following is documented:

    • Received at least 48 hours of antibiotic therapy for CABP and clinic notes document treatment failure (i.e., not by patient history or pulmonary imaging alone) with new or worsening symptoms while on pre-study therapy
    • Received 1 dose of a single, potentially effective, short-acting antibacterial drug or drug regimen for CABP within 24 hours before enrollment (limited to 25% of enrolled patients)
  4. Respiratory infection confirmed or suspected to be secondary to hospital-acquired or ventilator-associated pneumonia OR requires treatment in an intensive care setting, OR requires mechanical ventilation
  5. Current or suspected diagnosis of viral, fungal, or aspiration pneumonia, noninfectious causes of pulmonary infiltrates, lung cancer, cystic fibrosis, tuberculosis, empyema (not including sterile parapneumonic effusions)
  6. Known anatomical or pathological bronchial obstruction OR history of bronchiectasis OR GOLD Stage 4 COPD OR history of post obstructive pneumonia
  7. Severely compromised immune system
  8. Known history of Child-Pugh Class B or C liver disease
  9. History of post-antibiotic colitis within last 3 months
  10. Other exclusions include those described in the safety label for drugs in the quinolone and/or oxazolidinone classes such as QT prolongation, proarrhythmic conditions, concomitant use of drugs known to cause QT prolongation, peripheral neuropathy, tendon disorders, history of myasthenia gravis, liver disease, severe renal disease, seizures and concomitant use of MAO A or B inhibitor agents and adrenergic serotonergic agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02679573


Locations
Show Show 90 study locations
Sponsors and Collaborators
Melinta Therapeutics, Inc.
Investigators
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Study Director: Sue Cammarata, MD Melinta Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Melinta Therapeutics, Inc.:
Study Protocol  [PDF] December 4, 2017
Statistical Analysis Plan  [PDF] October 2, 2018

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Responsible Party: Melinta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02679573    
Other Study ID Numbers: ML-3341-306
2015-003026-14 ( EudraCT Number )
First Posted: February 10, 2016    Key Record Dates
Results First Posted: February 27, 2020
Last Update Posted: February 27, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Melinta Therapeutics, Inc.:
Pneumonia
Additional relevant MeSH terms:
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Delafloxacin
Pneumonia, Bacterial
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Bacterial Infections
Moxifloxacin
Linezolid
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Synthesis Inhibitors