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

Community Acquired Bacterial Pneumonia Clinical Trial

— DEFINE-CABP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02679573
• Other study ID #: ML-3341-306
• Secondary ID: 2015-003026-14
• Status: Completed
• Phase: Phase 3
• Start date: December 14, 2016
• Est. completion date: August 7, 2018

Study information

• Verified date: February 2020
• Source: Melinta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 860
• Est. completion date: August 7, 2018
• Est. primary completion date: July 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Community Acquired Bacterial Pneumonia
• Pneumonia
• Pneumonia, Bacterial

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Argentina	Melinta 306 Study Site	Buenos Aires
Argentina	Melinta 306 Study Site	Córdoba
Argentina	Melinta 306 Study Site	La Plata
Bulgaria	Melinta 306 Study Site	Pleven
Bulgaria	Melinta 306 Study Site	Ruse
Bulgaria	Melinta 306 Study Site	Sofia
Bulgaria	Melinta 306 Study Site	Stara Zagora
Colombia	Melinta 306 Study Site	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
Dominican Republic	Melinta 306 Study Site	Santo Domingo
Georgia	Melinta 306 Study Site	Tbilisi
Germany	Melinta 306 Study Site	Leverkusen
Germany	Melinta 306 Study Site	Munich
Hungary	Melinta 306 Study Site	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
Latvia	Melinta 306 Study Site	Daugavpils
Latvia	Melinta 306 Study Site	Liepaja
Latvia	Melinta 306 Study Site	Riga
Peru	Melinta 306 Study Site	Lima
Poland	Melinta 306 Study Site	Chrzanow
Poland	Melinta 306 Study Site	Katowice
Poland	Melinta 306 Study Site	Lodz
Poland	Melinta 306 Study Site	Wroclaw
Romania	Melinta 306 Study Site	Brasov
Romania	Melinta 306 Study Site	Bucharest
Romania	Melinta 306 Study Site	Craiova
Romania	Melinta 306 Study Site	Timisoara
Russian Federation	Melinta 306 Study Site	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
Serbia	Melinta 306 Study Site	Belgrade
Serbia	Melinta 306 Study Site	Kragujevac
Serbia	Melinta 306 Study Site	Nis
Serbia	Melinta 306 Study Site	Sremska Kamenica
Slovenia	Melinta 306 Study Site	Golnik
Slovenia	Melinta 306 Study Site	Ljubljana
South Africa	Melinta 306 Study Site	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
Spain	Melinta 306 Study Site	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
Ukraine	Melinta 306 Study Site	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
United States	Melinta 306 Study Site	Baltimore	Maryland
United States	Melinta 306 Study Site	Boston	Massachusetts
United States	Melinta 306 Study Site	Buffalo	New York
United States	Melinta 306 Study Site	Burlington	Massachusetts
United States	Melinta 306 Study Site	Butte	Montana
United States	Melinta 306 Study Site	Charlotte	North Carolina
United States	Melinta 306 Study Site	Cleveland	Ohio
United States	Melinta 306 Study Site	Coral Gables	Florida
United States	Melinta 306 Study Site	Corsicana	Texas
United States	Melinta 306 Study Site	Dayton	Ohio
United States	Melinta 306 Study Site	DeBary	Florida
United States	Melinta 306 Study Site	DeLand	Florida
United States	Melinta 306 Study Site	Fort Myers	Florida
United States	Melinta 306 Study Site	Franklin	Tennessee
United States	Melinta 306 Study Site	Louisville	Kentucky
United States	Melinta 306 Study Site	Miami	Florida
United States	Melinta 306 Study Site	Miami	Florida
United States	Melinta 306 Study Site	Montgomery	Alabama
United States	Melinta 306 Study Site	Natchitoches	Louisiana
United States	Melinta 306 Study Site	Newark	Delaware
United States	Melinta 306 Study Site	Newark	New Jersey
United States	Melinta 306 Study Site	Omaha	Nebraska
United States	Melinta 306 Study Site	Rapid City	South Dakota
United States	Melinta 306 Study Site	Saint Louis	Missouri
United States	Melinta 306 Study Site	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Melinta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Colombia,  Dominican Republic,  Georgia,  Germany,  Hungary,  Latvia,  Peru,  Poland,  Romania,  Russian Federation,  Serbia,  Slovenia,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	All-cause Mortality	Time to all-cause Mortality was assessed on Day 28.	Day 28 (+/- 2 days)