| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Community-Acquired Bacterial Pneumonia |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010120 |
| E.1.2 | Term | Community acquired pneumonia |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
EMA
To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with CABP at 5 to 10 days after the last dose of study drug (TOC) compared to IV to oral comparator study drug arm in the Modified ITT (ModITT) and Modified CE (ModCE) populations.
FDA
To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with 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
ITT population. |
|
| E.2.2 | Secondary objectives of the trial |
EMA
- To assess the clinical efficacy of IV to oral delafloxacin in adult subjects
with CABP based on ECR defined as improvement at
96 hours (± 24 hours) after the first dose of study drug compared to IV to oral moxifloxacin in the ModITT and ModCE populations.
- To assess the clinical efficacy of IV to oral delafloxacin in adult subjects
with CABP at the TOC visit compared to IV to oral
moxifloxacin in the Modified MITT (ModMITT) and Modified ME (ModME)
populations.
- To assess the microbiologic response to delafloxacin in respiratory pathogens in the ModMITT and ModME populations.
- To assess the safety and tolerability of IV to oral delafloxacin in adult subjects with CABP in safety population.
- To assess the all-cause mortality in adult subjects with CABP on Day 28 in ModITT.
- To assess delafloxacin PK in adult subjects with CABP in PK population.
FDA
Secondary objectives for FDA can be found at pages 34-35 of the current protocol amendment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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/mm^3 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
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
|
|
| E.4 | Principal exclusion criteria |
1. A medical history of significant hypersensitivity or allergic reaction to antibiotics of the quinolone or oxazolidinone class or study drug excipients in the judgment of 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
|
|
| E.5 End points |
| E.5.1 | 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. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
- 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) |
|
| E.5.2.1 | 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
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Matching Placebo to Delafloxacin oral, Moxifloxacin oral, Moxifloxacin IV and Linezolid IV |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 49 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Bulgaria |
| Colombia |
| Georgia |
| Germany |
| Greece |
| Hungary |
| Latvia |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| Slovenia |
| South Africa |
| Spain |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 22 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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