Clinical trial NCT02679573: Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults With Community-acquired Bacterial Pneumonia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Community Acquired Bacterial Pneumonia
Keywords: Pneumonia
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-02-10
Enrollment: 860
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Early Clinical Response
timeFrame: 96 (+/- 24) hours after the first dose of study drug
Secondary outcomes:
measure: Early Clinical Response Plus Improvement in Vital Signs and no Worsening of the 4 Symptoms
timeFrame: 96 (+/- 24) hours after the first dose of study drug
measure: Clinical Outcome at Test of Cure
timeFrame: 5 to 10 days after the last dose of study drug
measure: Clinical Outcome at End of Treatment
timeFrame: Up to 24 (+4) hours after the last dose of study drug
measure: Microbiologic Response
timeFrame: 5 to 10 days after the last dose of study drug
measure: All-cause Mortality
timeFrame: Day 28 (+/- 2 days)
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Melinta 306 Study Site
state: Alabama
city: Newark
country: United States
facility: Melinta 306 Study Site
state: Delaware
city: Coral Gables
country: United States
facility: Melinta 306 Study Site
state: Florida
city: DeBary
country: United States
facility: Melinta 306 Study Site
state: Florida
city: DeLand
country: United States
facility: Melinta 306 Study Site
state: Florida
city: Fort Myers
country: United States
facility: Melinta 306 Study Site
state: Florida
city: Miami
country: United States
facility: Melinta 306 Study Site
state: Florida
city: Miami
country: United States
facility: Melinta 306 Study Site
state: Florida
city: Louisville
country: United States
facility: Melinta 306 Study Site
state: Kentucky
city: Natchitoches
country: United States
facility: Melinta 306 Study Site
state: Louisiana
city: Baltimore
country: United States
facility: Melinta 306 Study Site
state: Maryland
city: Boston
country: United States
facility: Melinta 306 Study Site
state: Massachusetts
city: Burlington
country: United States
facility: Melinta 306 Study Site
state: Massachusetts
city: Saint Paul
country: United States
facility: Melinta 306 Study Site
state: Minnesota
city: Saint Louis
country: United States
facility: Melinta 306 Study Site
state: Missouri
city: Butte
country: United States
facility: Melinta 306 Study Site
state: Montana
city: Omaha
country: United States
facility: Melinta 306 Study Site
state: Nebraska
city: Newark
country: United States
facility: Melinta 306 Study Site
state: New Jersey
city: Buffalo
country: United States
facility: Melinta 306 Study Site
state: New York
city: Charlotte
country: United States
facility: Melinta 306 Study Site
state: North Carolina
city: Cleveland
country: United States
facility: Melinta 306 Study Site
state: Ohio
city: Dayton
country: United States
facility: Melinta 306 Study Site
state: Ohio
city: Rapid City
country: United States
facility: Melinta 306 Study Site
state: South Dakota
city: Franklin
country: United States
facility: Melinta 306 Study Site
state: Tennessee
city: Corsicana
country: United States
facility: Melinta 306 Study Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Melinta 306 Study Site
city: Córdoba
country: Argentina
facility: Melinta 306 Study Site
city: La Plata
country: Argentina
facility: Melinta 306 Study Site
city: Pleven
country: Bulgaria
facility: Melinta 306 Study Site
city: Ruse
country: Bulgaria
facility: Melinta 306 Study Site
city: Sofia
country: Bulgaria
facility: Melinta 306 Study Site
city: Stara Zagora
country: Bulgaria
facility: Melinta 306 Study Site
city: Barranquilla
country: Colombia
facility: Melinta 306 Study Site
city: Cali
country: Colombia
facility: Melinta 306 Study Site
city: Manizales
country: Colombia
facility: Melinta 306 Study Site
city: Medellín
country: Colombia
facility: Melinta 306 Study Site
city: Quindío
country: Colombia
facility: Melinta 306 Study Site
city: Santo Domingo
country: Dominican Republic
facility: Melinta 306 Study Site
city: Tbilisi
country: Georgia
facility: Melinta 306 Study Site
city: Leverkusen
country: Germany
facility: Melinta 306 Study Site
city: Munich
country: Germany
facility: Melinta 306 Study Site
city: Budapest
country: Hungary
facility: Melinta 306 Study Site
city: Debrecen
country: Hungary
facility: Melinta 306 Study Site
city: Deszk
country: Hungary
facility: Melinta 306 Study Site
city: Miskolc
country: Hungary
facility: Melinta 306 Study Site
city: Nyíregyháza
country: Hungary
facility: Melinta 306 Study Site
city: Szombathely
country: Hungary
facility: Melinta 306 Study Site
city: Daugavpils
country: Latvia
facility: Melinta 306 Study Site
city: Liepaja
country: Latvia
facility: Melinta 306 Study Site
city: Riga
country: Latvia
facility: Melinta 306 Study Site
city: Lima
country: Peru
facility: Melinta 306 Study Site
city: Chrzanow
country: Poland
facility: Melinta 306 Study Site
city: Katowice
country: Poland
facility: Melinta 306 Study Site
city: Lodz
country: Poland
facility: Melinta 306 Study Site
city: Wroclaw
country: Poland
facility: Melinta 306 Study Site
city: Braşov
country: Romania
facility: Melinta 306 Study Site
city: Bucharest
country: Romania
facility: Melinta 306 Study Site
city: Craiova
country: Romania
facility: Melinta 306 Study Site
city: Timisoara
country: Romania
facility: Melinta 306 Study Site
city: Arkhangel'sk
country: Russian Federation
facility: Melinta 306 Study Site
city: Moscow
country: Russian Federation
facility: Melinta 306 Study Site
city: Smolensk
country: Russian Federation
facility: Melinta 306 Study Site
city: St. Petersburg
country: Russian Federation
facility: Melinta 306 Study Site
city: Vsevolozhsk
country: Russian Federation
facility: Melinta 306 Study Site
city: Belgrade
country: Serbia
facility: Melinta 306 Study Site
city: Kragujevac
country: Serbia
facility: Melinta 306 Study Site
city: Nis
country: Serbia
facility: Melinta 306 Study Site
city: Sremska Kamenica
country: Serbia
facility: Melinta 306 Study Site
city: Golnik
country: Slovenia
facility: Melinta 306 Study Site
city: Ljubljana
country: Slovenia
facility: Melinta 306 Study Site
city: Benoni
country: South Africa
facility: Melinta 306 Study Site
city: Chatsworth
country: South Africa
facility: Melinta 306 Study Site
city: Krugersdorp
country: South Africa
facility: Melinta 306 Study Site
city: Middelburg
country: South Africa
facility: Melinta 306 Study Site
city: Phoenix
country: South Africa
facility: Melinta 306 Study Site
city: Port Elizabeth
country: South Africa
facility: Melinta 306 Study Site
city: Pretoria
country: South Africa
facility: Melinta 306 Study Site
city: Worcester
country: South Africa
facility: Melinta 306 Study Site
city: Badalona
country: Spain
facility: Melinta 306 Study Site
city: Barcelona
country: Spain
facility: Melinta 306 Study Site
city: Madrid
country: Spain
facility: Melinta 306 Study Site
city: Terrassa
country: Spain
facility: Melinta 306 Study Site
city: Valencia
country: Spain
facility: Melinta 306 Study Site
city: Dnipro
country: Ukraine
facility: Melinta 306 Study Site
city: Kharkiv
country: Ukraine
facility: Melinta 306 Study Site
city: Kyiv
country: Ukraine
facility: Melinta 306 Study Site
city: Poltava
country: Ukraine
facility: Melinta 306 Study Site
city: Vinnytsia
country: Ukraine
facility: Melinta 306 Study Site
city: Zaporizhia
country: Ukraine
facility: Melinta 306 Study Site
city: Zhytomyr
country: Ukraine
facility: Melinta 306 Study Site
Study officials:
affiliation: Melinta Therapeutics, Inc.
name: Sue Cammarata, MD
role: STUDY_DIRECTOR
References: