| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Community-Acquired Bacterial Pneumonia (CABP) |
|
| MedDRA Classification |
| 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 of this study 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 |
to evaluate the treatment effect of JNJ-32729463 on:
1)the daily signs and symptoms of CABP as compared to moxifloxacin;
2)percent of subjects with resolution of the signs and symptoms of CABP at Day 3
and Day 4 as compared to moxifloxacin
3)the per-pathogen microbiological response at Test of Cure (TOC) as compared to
moxifloxacin
4) the per-subject microbiological response at TOC as compared to
moxifloxacin
5) the clinical outcome at TOC as compared to moxifloxacin in subjects with
S. pneumoniae
6) the rate of superinfections or new infections
7) the time to oral switch as compared to moxifloxacin
8) all-cause mortality within 30 days of start of study
medication
9.) To determine the safety and tolerability profiles of JNJ-32729463
10. To evaluate adverse events (AEs) of special interest |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible for enrollment in this study, each of the following criteria must be satisfied with a YES answer (unless not applicable):
1 Subject is male or female between the ages of 18 and 75 yrs, 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.
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 |
To be eligible for this study, each of the following criteria must be satisfied with a NO answer:
1 Subject intubated at randomization OR subject is a candidate for enrollment into the open-label S. aureus arm and has been intubated >12 hrs prior to randomization. (This does not exclude subjects who require positive-pressure breathing, such as continuous positive airway pressure or bilevel positive airway pressure)
2 Subject has mild CABP with a PORT score of less than II
3 Subject has received any systemic antibiotics within the last 2 wks before randomization
PRIOR ANTIBIOTIC USE: In general, subjects who have received any prior antibiotics within the past 2 wks before randomization SHOULD NOT BE ENROLLED. However, 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 antibiotic within 12 hrs prior to randomization
4 Subject has received ceftriaxone, azithromycin, any fluoroquinolone or doxycycline (these are not considered to be short-acting antibiotics) or any long acting antibiotic defined as an antibiotic with >8 hr plasma half-life within the last 2 wks before randomization
5 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
6 Subject has viral, fungal, mycobacterial, or atypical pneumonia. 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
7 Subject has pneumonia suspected to be secondary to aspiration
8 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
9 Subject has healthcare-associated pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia or subject has been hospitalized for greater than 72 hrs for any reason 30 days before randomization (excluding the 24 hr period before enrollment)
10 Subject has known bronchial obstruction or a history of postobstructive pneumonia. (This does not exclude subjects who have COPD)
11 Subject has primary lung cancer or another malignancy metastatic to the lungs
12 Subject is receiving or has received chemotherapeutic agents within the past 3 mths
13 Subject has cystic fibrosis, known or suspected Pneumocystis jiroveci (carinii) pneumonia, or known or suspected active tuberculosis
14 In the past 4 wks 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
15 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. Subjects on current treatment with (or with a history of prior treatment with) inhaled steroids are not excluded from this study
16 Subject has a history of a hypersensitivity reaction (eg, urticaria or anaphylaxis) to any quinolone including moxifloxacin
17 Subject has used any investigational agent concomitantly or within 30 days or 5 half-lives, whichever is longer, before receiving study medication
18 Subject is pregnant, breastfeeding, or may be pregnant
19 Subject has a history of long QT syndrome, or subject’s QTc interval is >450 ms as read by the local reader at Baseline
20 Subject is known to have clinically relevant bradycardia
21 Subject is known to have New York Heart Association class IV heart failure
22 Subject is known to have a history of symptomatic ventricular arrhythmias
23 Subject is receiving class Ia or class III antiarrhythmic agents
24 Subject has had episodes of symptomatic hypoglycemia within the past 30 days
25 Subject has a known seizure disorder or history of epilepsy. Subjects with a history of childhood febrile seizures are permitted to enroll in the study
26 Subject has known current clinically significant hepatic disease, such as a history of chronic active hepatitis (eg, chronic hepatitis B or hepatitis C)
27 Subject has any of the following exclusionary laboratory results:
a Serum creatinine clearance result <60 mL/min (using Cockcroft-Gault formula)
b Total bilirubin result ≥3 times the upper limit of normal
c Alanine aminotransferase and/or aspartate aminotransferase ≥2 times the upper limit of normal |
|
| 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.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 | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 4 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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