A STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVENOUS TO ORAL DELAFLOXACIN IN ADULT SUBJECTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2015-003026-14-BG
• Date of registration: 26/01/2016
• Prospective Registration: Yes
• Primary sponsor: Melinta Therapeutics, Inc.
• Public title: A STUDY TO EVALUATE THE SAFETY AND EFFICACY OF INTRAVENOUS TO ORAL DELAFLOXACIN IN ADULT SUBJECTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA
• Scientific 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
• Date of first enrolment: 01/03/2016
• Target sample size: 860
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003026-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: I.V. to oral switch; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Matching Placebo to Dela oral, Moxi oral and Moxi i.v.; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Melinta Clinical Trials
• Affiliation: Melinta Therapeutics, Inc.

• Name: Melinta Clinical Trials
• Affiliation: Melinta Therapeutics, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects 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°C)
• Hypothermia (oral temperature < 35°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/mm3
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.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 559
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 301

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 7days before enrollment
• one dose of a single, potentially effective, short-acting antibacterial drug or drug regimen for CABP within 24 hours before enrollment is allowed - limited to 25% of enrolled patients
4. Respiratory infection confirmed or suspected to be secondary to hospital-required or ventilator-associated pneumonia or requires treatment in an intensive care setting, or 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 obstruction or history of bronchiectasis or GOLD Stage 4 COPD or history of post obstructive pneumonia
7. Severely compromised immune system
8. 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Community-Acquired Bacterial Pneumonia
MedDRA version: 20.1 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Delafloxacin
Product Code: RX-3341-83
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Delafloxacin meglumine
CAS Number: 352458-37-8
Current Sponsor code: RX-3341-83
Other descriptive name: DELAFLOXACIN MEGLUMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Product Name: Delafloxacin oral tablet
Product Code: RX-3341-83
Pharmaceutical Form: Tablet
INN or Proposed INN: Delafloxacin meglumine
CAS Number: 352458-37-8
Current Sponsor code: RX-3341-83
Other descriptive name: DELAFLOXACIN MEGLUMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 450-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Moxifloxacin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Moxifloxacin
CAS Number: 186826-86-8
Other descriptive name: MOXIFLOXACIN HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.6-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Product Name: Moxifloxacin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Moxifloxacin
CAS Number: 186826-86-8
Other descriptive name: MOXIFLOXACIN HYDROCHLORIDE
Concentration unit: mg milligram(s)

Primary Outcome(s)

Primary end point(s): The Clinical Outcome responder rate at 5 to 10 days after the last dose of
study drug (TOC) defined as resolution or near resolution of the
symptoms of CABP present at study entry, and no use of additional
antimicrobial therapy for the current infection, and no new symptoms
associated with the current CABP infection
(success) in the ModITT and ModCE populations.

Secondary Objective: • To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with CABP based on Clinical Outcome at the Test of Cure (TOC) visit, 5 to 10 days after the last dose of study drug, compared to IV to oral comparator study drug arm in the CE and ITT populations.
• To assess the noninferiority of clinical efficacy of IV to oral delafloxacin in adult subjects with CABP based on ECR compared to IV to oral moxifloxacin in the microbiologic ITT (MITT) population.
• To assess the microbiologic response to delafloxacin in respiratory pathogens.
• To assess the safety and tolerability of IV to oral delafloxacin in adult subjects with CABP.
• To assess the all-cause mortality in adult subjects with CABP on Day 28.
• To assess delafloxacin pharmacokinetics (PK) in adult subjects with CABP.

Main Objective: The primary objective is to assess the noninferiority of clinical efficacy of intravenous (IV) to oral delafloxacin in adult subjects with community-acquired bacterial pneumonia (CABP) based on Early Clinical Response (ECR) defined as improvement at 96 hours (± 24 hours) after the first dose of study drug compared to IV to oral moxifloxacin in the Intent-to-Treat (ITT) population.

Timepoint(s) of evaluation of this end point: Days 5 to 10

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Clinical Outcome at the Test of Cure (TOC) visit, 5 to 10 days after the last dose of study drug
All-cause mortality (ModITT) - Day 28
96 h ± 24 h for Early Clinical Response

Secondary end point(s): ECR defined as improvement at 96 hours (± 24 hours) after first dose
of study drug in at least 2 of the following symptoms: chest pain, frequency or severity of cough, amount and quality of productive sputum and difficulty breathing and no worsening of any of the other symptoms in the ModITT and ModCE populations
- ECR with the addition of improvement in vital signs and no worsening of the 4 symptoms required as Response in the ModITT and ModCE populations
- Clinical Outcome at EOT (ModITT and ModCE)
- Clinical Outcome at TOC in the ModMITT and ModME populations
- Microbiologic response (ModMITT and ModME)
- All-cause mortality (ModITT)

Secondary ID(s)

2015-003026-14-HU

ML-3341-306

NCT02679573

Source(s) of Monetary Support

Melinta Therapeutics, Inc.

Ethics review

Status: Approved
Approval date:
Contact: