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

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

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.

Study Overview

• Status: Completed
• Conditions: Community Acquired Bacterial Pneumonia
• Intervention / Treatment: Drug: Delafloxacin; Drug: Moxifloxacin; Drug: Linezolid

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.

• Study Type: Interventional
• Enrollment (Actual): 860
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Melinta 306 Study Site
  • Córdoba, Argentina
    • Melinta 306 Study Site
  • La Plata, Argentina
    • Melinta 306 Study Site
• Bulgaria
  • Pleven, Bulgaria
    • Melinta 306 Study Site
  • Ruse, Bulgaria
    • Melinta 306 Study Site
  • Sofia, Bulgaria
    • Melinta 306 Study Site
  • Stara Zagora, Bulgaria
    • Melinta 306 Study Site
• Colombia
  • Barranquilla, Colombia
    • Melinta 306 Study Site
  • Cali, Colombia
    • Melinta 306 Study Site
  • Manizales, Colombia
    • Melinta 306 Study Site
  • Medellín, Colombia
    • Melinta 306 Study Site
  • Quindío, Colombia
    • Melinta 306 Study Site
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Melinta 306 Study Site
• Georgia
  • Tbilisi, Georgia
    • Melinta 306 Study Site
• Germany
  • Leverkusen, Germany
    • Melinta 306 Study Site
  • Munich, Germany
    • Melinta 306 Study Site
• Hungary
  • Budapest, Hungary
    • Melinta 306 Study Site
  • Debrecen, Hungary
    • Melinta 306 Study Site
  • Deszk, Hungary
    • Melinta 306 Study Site
  • Miskolc, Hungary
    • Melinta 306 Study Site
  • Nyíregyháza, Hungary
    • Melinta 306 Study Site
  • Szombathely, Hungary
    • Melinta 306 Study Site
• Latvia
  • Daugavpils, Latvia
    • Melinta 306 Study Site
  • Liepaja, Latvia
    • Melinta 306 Study Site
  • Riga, Latvia
    • Melinta 306 Study Site
• Peru
  • Lima, Peru
    • Melinta 306 Study Site
• Poland
  • Chrzanow, Poland
    • Melinta 306 Study Site
  • Katowice, Poland
    • Melinta 306 Study Site
  • Lodz, Poland
    • Melinta 306 Study Site
  • Wroclaw, Poland
    • Melinta 306 Study Site
• Romania
  • Braşov, Romania
    • Melinta 306 Study Site
  • Bucharest, Romania
    • Melinta 306 Study Site
  • Craiova, Romania
    • Melinta 306 Study Site
  • Timisoara, Romania
    • Melinta 306 Study Site
• Russian Federation
  • Arkhangel'sk, Russian Federation
    • Melinta 306 Study Site
  • Moscow, Russian Federation
    • Melinta 306 Study Site
  • Smolensk, Russian Federation
    • Melinta 306 Study Site
  • St. Petersburg, Russian Federation
    • Melinta 306 Study Site
  • Vsevolozhsk, Russian Federation
    • Melinta 306 Study Site
• Serbia
  • Belgrade, Serbia
    • Melinta 306 Study Site
  • Kragujevac, Serbia
    • Melinta 306 Study Site
  • Nis, Serbia
    • Melinta 306 Study Site
  • Sremska Kamenica, Serbia
    • Melinta 306 Study Site
• Slovenia
  • Golnik, Slovenia
    • Melinta 306 Study Site
  • Ljubljana, Slovenia
    • Melinta 306 Study Site
• South Africa
  • Benoni, South Africa
    • Melinta 306 Study Site
  • Chatsworth, South Africa
    • Melinta 306 Study Site
  • Krugersdorp, South Africa
    • Melinta 306 Study Site
  • Middelburg, South Africa
    • Melinta 306 Study Site
  • Phoenix, South Africa
    • Melinta 306 Study Site
  • Port Elizabeth, South Africa
    • Melinta 306 Study Site
  • Pretoria, South Africa
    • Melinta 306 Study Site
  • Worcester, South Africa
    • Melinta 306 Study Site
• Spain
  • Badalona, Spain
    • Melinta 306 Study Site
  • Barcelona, Spain
    • Melinta 306 Study Site
  • Madrid, Spain
    • Melinta 306 Study Site
  • Terrassa, Spain
    • Melinta 306 Study Site
  • Valencia, Spain
    • Melinta 306 Study Site
• Ukraine
  • Dnipro, Ukraine
    • Melinta 306 Study Site
  • Kharkiv, Ukraine
    • Melinta 306 Study Site
  • Kyiv, Ukraine
    • Melinta 306 Study Site
  • Poltava, Ukraine
    • Melinta 306 Study Site
  • Vinnytsia, Ukraine
    • Melinta 306 Study Site
  • Zaporizhia, Ukraine
    • Melinta 306 Study Site
  • Zhytomyr, Ukraine
    • Melinta 306 Study Site
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36106
      • Melinta 306 Study Site
  • Delaware
    • Newark, Delaware, United States, 19718
      • Melinta 306 Study Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Melinta 306 Study Site
    • DeBary, Florida, United States, 32713
      • Melinta 306 Study Site
    • DeLand, Florida, United States, 32720
      • Melinta 306 Study Site
    • Fort Myers, Florida, United States, 33901
      • Melinta 306 Study Site
    • Miami, Florida, United States, 33126
      • Melinta 306 Study Site
    • Miami, Florida, United States, 33185
      • Melinta 306 Study Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Melinta 306 Study Site
  • Louisiana
    • Natchitoches, Louisiana, United States, 71457-6215
      • Melinta 306 Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Melinta 306 Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Melinta 306 Study Site
    • Burlington, Massachusetts, United States, 01805
      • Melinta 306 Study Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55104
      • Melinta 306 Study Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Melinta 306 Study Site
  • Montana
    • Butte, Montana, United States, 59701
      • Melinta 306 Study Site
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Melinta 306 Study Site
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Melinta 306 Study Site
  • New York
    • Buffalo, New York, United States, 14215
      • Melinta 306 Study Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Melinta 306 Study Site
  • Ohio
    • Cleveland, Ohio, United States, 44106-5029
      • Melinta 306 Study Site
    • Dayton, Ohio, United States, 45402
      • Melinta 306 Study Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Melinta 306 Study Site
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Melinta 306 Study Site
  • Texas
    • Corsicana, Texas, United States, 75110
      • Melinta 306 Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: Zyvox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Clinical Response	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.	96 (+/- 24) hours after the first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Clinical Response Plus Improvement in Vital Signs and no Worsening of the 4 Symptoms	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.	96 (+/- 24) hours after the first dose of study drug
Clinical Outcome at Test of Cure	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.	5 to 10 days after the last dose of study drug
Clinical Outcome at End of Treatment	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.	Up to 24 (+4) hours after the last dose of study drug
Microbiologic Response	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 to 10 days after the last dose of study drug
All-cause Mortality	Time to all-cause Mortality was assessed on Day 28.	Day 28 (+/- 2 days)

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2016
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): August 7, 2018

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 14, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: 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; Protein Synthesis Inhibitors; Linezolid; Moxifloxacin
• Other Study ID Numbers: ML-3341-306; 2015-003026-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No