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: 3 September 2018
• Main ID: EUCTR2015-003026-14-LV
• Date of registration: 21/01/2016
• 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: 15/03/2016
• 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 18 years of age or older.
• Patients from a nursing home setting may be enrolled if they are normally ambulatory and are not on enteral feeding
2. Evidence of acute onset of CABP.
Subjects must have at least 2 of the following clinical signs and symptoms (new or worsening):
• Cough
• Production of purulent sputum consistent with a bacterial infection
• Difficulty breathing (dyspnea)
• Chest pain due to pneumonia
Subjects must also have at least 3 of the following findings:
• Fever (oral temperature > 38°C or equivalent) within 24 hours prior to randomization
• Hypothermia (oral temperature < 35°C or equivalent) within 24 hours prior to randomization
• Tachycardia (> 100 beats per minute)
• Tachypnea (elevated respiratory rate >18 breaths per minute)
Subjects must also 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 flow rate)
• 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 (e.g., chest radiograph [CXR] [posteroanterior and lateral preferred; single view acceptable if conclusive] or computed tomography [CT] of thorax) as per local standard of care within 48 hours before the first dose of study drug.
4. PORT risk class of II, III, IV or V (PSI Score greater than 50). Subjects may be initially screened based on meeting CURB-65 score of 2 to 4. PORT risk class II will be limited to 25% of randomized subjects.
5. In the opinion of the investigator, the subject 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.
6. Females of childbearing potential (including females less than 2 years post-menopausal) must have a negative pregnancy test prior to enrollment. Sexually active women and men with partners of childbearing potential must agree to use an acceptable form of contraception, as determined by the investigator (e.g., abstinence, oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy) during participation in the study and through the Follow-up Visit (Day 28). Female partners of male subjects should also use an additional reliable method of contraception, such as spermicide with male or female condoms, cervical sponge, intrauterine device, cervical cap or diaphragm, or oral, implantable, transdermal, or injectable contraceptives during study and through the Follow-up Visit (Day 28).
7. In the opinion of the investigator, the subject must be able and willing to comply with protocol requirements.
8. A written, voluntarily signed informed consent must be obtained from the subject or where allowed by local regulations, legally authorized representative, in accordance with local regulations, before the initiation of any study-related procedures. The subject or legally authorized representative must be able to read and/or understand the informed consent form as required by the legal jurisdiction and the institutional review board/independent ethics committee where the subjec
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
• 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: 19.1 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)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Linezolid
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Linezolid
CAS Number: 165800-03-3
Other descriptive name: LINEZOLID
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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.

Primary end point(s): The primary efficacy endpoint is the 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 ITT population.

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: Day 4

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are:
• ECR with the addition of improvement in vital signs and no worsening of the 4 symptoms required as Response in the ITT populations.
• Clinical Outcome at TOC (Clinically Evaluable [CE] and ITT population)
• Clinical outcome at the end of treatment (EOT)
• ECR in MITT population
• Microbiologic response (ME and MITT)
• All-cause mortality (ITT)

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 (ITT)- Day 28
96 h ± 24 h for Early Clinical Response

Secondary ID(s)

ML-3341-306

2015-003026-14-HU

NCT02679573

Source(s) of Monetary Support

Melinta Therapeutics, Inc.