| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Community-Acquired Pneumonia |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10010120 |
| E.1.2 | Term | Community acquired pneumonia |
|
| 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 |
| To compare the efficacy, safety and tolerance of 2 different dose levels of oral NXL103 with oral amoxicillin in the treatment of community-acquired pneumonia in adults. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the relationship between the plasma pharmacokinetics of NXL103 (and its components PI and PII) and the clinical and bacteriological outcome. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Only patients with mild to moderately severe (The inclusion and exclusion criteria are built in such a way to include only subjects with CURB-65 score 0 or 1 see Appendix I) pneumonia will be included in this study.
Informed consent must be obtained for all subjects before enrollment in the study.
Subjects meeting all of the following criteria will be considered for admission to the study:
• Adult male subjects aged 18 to 70 years, Female subjects who have been postmenopausal for at least 1 year or is surgically incapable of bearing children.
• Subjects with diagnosis of acute CAP based upon:
new onset of at least two of the following clinical signs and symptoms:
• cough
• production of purulent or rusty sputum
• auscultatory findings [such as rales, pleural rubs and/or evidence of pulmonary consolidation (i.e., dullness on percussion, bronchial breath sounds, egophony)]
• dyspnea or tachypnea (particularly if progressive in nature) or pleuritic chest pain
and at least one of the following:
• fever (oral temperature > 38oC or tympanic temperature > 38.5oC or rectal temp. > 39oC)
• elevated total peripheral white blood cell count >10,000/mm3 or > 15 band forms, regardless of total peripheral white count
AND
chest x-ray findings which support a clinical diagnosis of bacterial pneumonia (e.g. presence of presumably new infiltrate(s) or lobar consolidation or segmental consolidation).
• Hospitalized (for study purpose or as is the local practice) or out-patients
• Subjects should have specimens collected for bacteriological documentation within 24 hours prior to enrollment. Specimens should include:
respiratory/sputum samples for Gram stain, cultures, susceptibility testing.
blood samples for culture.
Note: Subjects will be enrolled based upon investigator assessment of x-ray, after obtaining a report from a qualified radiologist. Subjects will be enrolled before the bacteriological results are available.
No patient is allowed to enter this study more than once.
|
|
| E.4 | Principal exclusion criteria |
• Subjects with severe CAP, defined as those requiring either intensive care unit (ICU) admission, parenteral antibiotic treatment, or demonstrating at least one of the following conditions:
respiratory frequency > 30 breaths/minute
chest radiograph showing bilateral involvement or involvement of multiple lobes
shock (systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg)
altered mental status (disorientation to person, place, or time that is not known to be chronic, lethargy, stupor, or coma)
< 90% O2 saturation (by pulse oximetry) or a PaO2 < 60 mm Hg
total peripheral white blood cell count < 4,000/mm3
requirement for mechanical ventilation
requirement for vasopressors for more than 4 hours
urine output lower than 20 mL/h or total urine output lower than 80 mL in 4 hours, unless another explanation is available, or acute renal failure requiring dialysis
blood urea > 7mmol/L
• Subjects with respiratory tract infections attributable to sources other than community-acquired bacterial infection
• Subjects with any concomitant pulmonary disease, condition or complications that could confound the interpretation or evaluation of drug efficacy or safety
• Subjects with neoplastic lung disease (lung cancer) or another malignancy metastatic to the lungs, and/or requiring chemotherapeutic interventions for this or other neoplasms.
• Subjects who are receiving other medications, including other systemic antimicrobial agents, or who have other disease conditions or infections that could interfere with the evaluation of drug efficacy or drug safety.
• Subjects who have received more than 24 hours of treatment with other antibiotics, within the 7 days prior to enrollment in the study.
• Subjects treated within the 7 days prior to enrollment with azithromycin or dirithromycin, ceftriaxone, quinolones, amoxicillin and amoxicillin/clavulanic acid.
• Subjects with a microbiologically documented infection with a pathogen known prior to inclusion to be resistant to the study medications.
• Subjects with known or suspected hypersensitivity to, or a known or suspected serious adverse reaction to the study medication, macrolide antibiotics, or β-lactam antibiotics.
• Subjects receiving probenecid treatment.
• Subjects who will require on-study treatment with medications known to have contraindicated drug interactions with the study medication and/or macrolides in general, including but not limited to:
Ergot alkaloids derivatives, terfenadine, cisapride, astemizole, pimozide, cholinesterase inhibitors (e.g., tacrine, donepezil, physostigmine), ketamine, cardiac glycosides (e.g., digoxin), St. John’s Wort, ketoconazole, itraconazole, quinidine, and disopyramide
• Subjects with known long QTc syndrome, sick sinus syndrome, bradycardia (heart rate of < 50 beats/minute), or severe hypokalemia.
• Subjects who have received any investigational drug within 1 month prior to study entry or such treatment is planned for during the study period.
• Subjects with progressively fatal disease; life expectancy 3 months.
• Subjects with any concomitant condition, including clinically relevant cardiovascular, neurologic, endocrine, or other major systemic disease that make implementation of the protocol or interpretation of the study results difficult.
• Subjects with a recent (within previous 3 months) history of drug or alcohol abuse.
• Subjects with impaired hepatic function, as shown by any of the following:
ALAT and/or ASAT 3 times the upper limit of the reference range
Bilirubin > 2 times the upper limit of reference range (except for Gilbert’s disease)
Prothrombin time (PT) 1.3 times the control
Encephalopathy
• Subjects with impaired renal function, as shown by creatinine clearance 50 mL/min (creatinine clearance may be estimated by formula, see Appendix A).
• Breast feeding or pregnant women
• Immunocompromised subjects
• Subjects with a mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
• Subject unlikely to comply with the protocol, (e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study).
In order to document the reason(s) for not including potential study subject(s), a potential patient roster (supplied by Sponsor) will be maintained by each investigator. All patients presenting with pneumonia during the study period will be entered (including reasons for non inclusion in the study) in this roster. A copy of this roster must be returned to Sponsor at the end of the study (after having removed patient's name).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Clinical cure or failure seven days after the end of treatment. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | No |
| 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 | 42 |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 15 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 15 |
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