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

Phase 3

Completed

• Conditions: Community Acquired Bacterial Pneumonia
• Interventions: Drug: Moxifloxacin; Drug: Delafloxacin; Drug: Linezolid

• Registration Number: NCT02679573
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2016-01-27
• Study First Submitted QC: 2016-02-05
• Study First Posted: 2016-02-10
• Study Start: 2016-12-14
• Primary Completion: 2018-07-31
• Study Completion: 2018-08-07
• Disposition First Submitted: 2019-07-18
• Disposition First Submitted QC: 2019-07-18
• Disposition First Posted: 2019-07-29
• Results First Submitted: 2019-12-10
• Status Verified: 2020-02
• Results First Submitted QC: 2020-02-14
• Last Update Submitted: 2020-02-14
• Results First Posted: 2020-02-27
• Last Update Posted: 2020-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 860

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moxifloxacin/Linezolid	Moxifloxacin	IV moxifloxacin with potential to switch to oral moxifloxacin, and potential to switch moxifloxacin to IV linezolid for confirmed MRSA
Delafloxacin	Delafloxacin	IV delafloxacin with potential to switch to oral delafloxacin
Moxifloxacin/Linezolid	Linezolid	IV moxifloxacin with potential to switch to oral moxifloxacin, and potential to switch moxifloxacin to IV linezolid for confirmed MRSA

Primary Outcome Measures

Name	Time	Method
Early Clinical Response	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

Name	Time	Method
Microbiologic Response	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.
Early Clinical Response Plus Improvement in Vital Signs and no Worsening of the 4 Symptoms	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.
Clinical Outcome at Test of Cure	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.
Clinical Outcome at End of Treatment	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.
All-cause Mortality	Day 28 (+/- 2 days)	Time to all-cause Mortality was assessed on Day 28.

Trial Locations

Locations (1)

Melinta 306 Study Site; 🇺🇦 Zhytomyr, Ukraine