| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Community-Acquired Bacterial Pneumonia (CABP) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Infection of the lungs (pneumonia) requiring antibiotic treatment |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004051 |
| E.1.2 | Term | Bacterial pneumonia, unspecified |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
| The primary objective is to demonstrate noninferiority in clinical success rates between JNJ 32729463 and moxifloxacin for subjects with CABP. |
|
| E.2.2 | Secondary objectives of the trial |
Treatment effect of JNJ 32729463 on daily signs & symptoms of CABP compared to moxifloxacin
Treatment effect of JNJ 32729463 on % of subjects with resolution of signs & symptoms of CABP at Day 3 and Day 4 compared to moxifloxacin
Treatment effect of JNJ 32729463 on per-pathogen microbiological response at TOC compared to moxifloxacin
Treatment effect of JNJ 32729463 on per-subject microbiological response at TOC compared to moxifloxacin
Treatment effect of JNJ 32729463 on clinical outcome at TOC compared to moxifloxacin in subjects with S. pneumoniae
Treatment effect of JNJ 32729463 on rate of superinfections or new infections compared to moxifloxacin
Treatment effect of JNJ 32729463 on time to oral switch compared to moxifloxacin
All-cause mortality within 30 days of start of study medication
Safety & tolerability profiles of JNJ 32729463 compared with those of moxifloxacin in subjects with CABP
Evaluate AEs after treatment with JNJ 32729463 or moxifloxacin |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Open Label treatment at selected sites in the USA only |
|
| E.3 | Principal inclusion criteria |
1. Subject is male or female between the ages of 18 and 85 years, inclusive.
2. If the subject is female and of childbearing potential, the subject agrees to use an acceptable form of contraception. Acceptable forms of contraception for subject or partner include condoms with spermicide gel, diaphragm with spermicide gel, coil (intrauterine device), surgical sterilization, vasectomy, oral contraceptive pill, depot progesterone injections, and abstinence.
3. Subject has CABP requiring hospitalization with a PORT score of II or greater (Appendix 3).
4. Subject has 3 or more of the following clinical signs and symptoms:
a. Cough with production of purulent sputum
b. Dyspnea or tachypnea
c. Chest pain
d. Fever or hypothermia
i. Fever is defined as body temperature >38°C (100.4°F) taken orally, >38.5°C (101.3°F) tympanically, or >39°C (102.2°F) rectally.
ii. Hypothermia is defined as body temperature <35°C (95°F).
e. Clinical findings of pulmonary consolidation (eg, dullness on percussion, bronchial breath sounds, or egophony)
5. Subject’s chest x ray shows the presence of new infiltrates in a lobar or multilobar distribution characteristic of bacterial pneumonia. Subjects with the presence of necrotizing lesions characteristic of S. aureus pneumonia are eligible for enrollment in the open-label JNJ 32729463 treatment arm for S. aureus pneumonia.
6. Subject is able to generate an adequate sputum specimen. An adequate sputum specimen is a specimen that has fewer than 10 squamous epithelial cells and more than 25 polymorphonuclear cells per low power field (100× magnification). Respiratory secretions may be obtained by any of the following means:
a. deep expectoration
b. bronchoscopy with bronchoalveolar lavage or protected-brush sampling
7. Subject, or legally authorized representative, is able to provide written and voluntary informed consent. |
|
| E.4 | Principal exclusion criteria |
1. Subject is intubated at the time of consent OR subject is a candidate for enrollment into the open-label S. aureus arm and has been intubated greater than 12 hours prior to randomization. (This does not exclude subjects who require positive-pressure breathing, such as continuous positive airway pressure or bilevel positive airway pressure. Also, patients who require intubation after randomization may remain in the study.)
2. Subject has mild CABP with a PORT score of less than II.
3. Subject has received any systemic antibiotics within the last 96 hours before randomization, unless:
a. Subject is HIV negative and received treatment for a respiratory infection with any antibiotic, EXCEPT a fluoroquinolone, for a treatment course > 48 hours and < 6 days, and meets the following criteria for clinical failure:
i. Sputum gram stain shows fewer than 10 squamous epithelial cells and more than 25 polymorphonuclear cells per low-power field (100× magnification) and at least 1 predominant microorganism consistent with CABP; &
ii. Subject has at least one of the following:
- Progression of symptoms of CABP
- Development of new/additional symptoms of CABP
- Development of new/additional chest x-ray findings consistent with CABP
These subjects are NOT eligible for enrollment if they test positive for influenza at Baseline via rapid test. Subjects previously treated with a fluoroquinolone are not eligible for enrollment even if they meet the criteria for clinical failure.
b. Recognizing current standards of care, if one is unable to initiate study medication infusion in an acceptable time frame, subjects are eligible for enrollment if, by standard of care, they have received a single dose of a single short-acting (defined as an antibiotic with <8 hour plasma half-life) antibiotic, or ceftriaxone, within 24 hours prior to randomization. Subjects who receive azithromycin, any fluoroquinolone, or doxycycline within 96 hours prior to randomization are NOT eligible for enrollment (these are not considered to be short-acting antibiotics).
4. Subject has an infection that necessitates the use of a concomitant antibacterial agent in addition to study medication; the use of topical agents is allowed.
5. Subject has viral, fungal, mycobacterial, or atypical pneumonia as a primary diagnosis. However:
a. A subject who tests positive for influenza via rapid test at Baseline is eligible for enrollment if the subject has simultaneous suspected CABP demonstrated by the predominance of a bacterial organism consistent with CABP on sputum Gram Stain.
b. A subject who has tested positive for influenza virus >5 days prior to study entry, who has clinically worsened, and whose chest radiograph is now consistent with a new infiltrate suspicious for bacterial pneumonia (including small necrotizing abscesses characteristic of S. aureus pneumonia) may be entered in the open-label JNJ 32729463 treatment arm for S. aureus pneumonia.
6. Subject has pneumonia suspected to be secondary to aspiration.
7. Subject has primary, solitary lung abscess. Small, multiple, necrotizing abscesses suspicious for S. aureus pneumonia may be entered into the open-label JNJ 32729463 treatment arm for S. aureus pneumonia.
8. Subject has healthcare-associated pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia or subject has been hospitalized for greater than 72 hours for any reason 30 days before randomization (excluding the 24 hour period before enrollment).
9. Subject has known bronchial obstruction or a history of postobstructive pneumonia. (This does not exclude subjects who have chronic obstructive pulmonary disease.)
10. Subject has primary lung cancer or another malignancy metastatic to the lungs.
11. Subject is receiving or has received chemotherapeutic agents within the past 3 months.
12. Subject has cystic fibrosis, known or suspected Pneumocystis jiroveci (carinii) pneumonia, or known or suspected active tuberculosis.
13. In the past 4 weeks before randomization, the subject has shown clinically significant disease of immune function (eg, current CD4 <200, current neutrophil count <1000/µL). Subjects with human immunodeficiency virus are allowed if they have a CD4 count >200 at Baseline.
14. Subject has received systemic steroids at a dose ≥10 mg/day of prednisone (or its equivalent) or other chronic immunosuppressive therapy such as disease-modifying antirheumatic drugs or interferons within the 6 weeks before Baseline. However, subjects who receive a one-time dose of systemic steroids within 24 hours of enrollment and those subjects on current treatment with (or with a history of prior treatment with) inhaled steroids are not excluded from this study.
15. Subject has a history of a hypersensitivity reaction (eg, urticaria or anaphylaxis) to any quinolone, including moxifloxacin, or any of their components.
For criteria 16 to 29 please see protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is subject clinical outcome based on complete resolution of signs and symptoms of CABP. The subject’s response to therapy will be based on a comparison of the subject’s baseline signs and symptoms and other laboratory parameters with the subject’s evaluation at the TOC visit. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| TOC (non-inferiority) day 19 (approximately) from baseline |
|
| E.5.2 | Secondary end point(s) |
1. Daily signs and symptoms of CABP
2. Percent of subjects with resolution of the signs and symptoms of CABP at Day 3 and Day 4
3. Per-pathogen microbiological response at TOC
4. Per-subject microbiological response at TOC
5. Clinical outcome at TOC in subjects with S. pneumoniae
6. Rate of superinfections or new infections
7. Time to oral switch
8. All-cause mortality within 30 days of start of study medication |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Stated in section E.5.2
TOC (non-inferiority) day 19 (approximately) from baseline
Safety endpoints from baseline to day 30 (see protocol section 7.1 Appendix 1: Schedule of Study Procedures) |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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 | No |
| E.8.2.3.1 | Comparator description |
|
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| 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 |
| Brazil |
| Bulgaria |
| Canada |
| Chile |
| Colombia |
| Germany |
| Hungary |
| Israel |
| Peru |
| Poland |
| Romania |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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