A double blind, multicentre, multinational, randomized, double dummy, three-arm parallel-group comparative study of the efficacy, safety and tolerance of oral NXL103 (500 mg twice daily) versus NXL103 (600 mg twice daily) versus oral amoxicillin (1000 mg three times daily) in the treatment of community-acquired pneumonia in adults

• Conditions: Community-Acquired Pneumonia; MedDRA version: 9.1Level: LLTClassification code 10010120Term: Community acquired pneumonia

• Registration Number: EUCTR2007-001735-66-DE
• Lead Sponsor: ovexel S. A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-27
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 ß-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 AS

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified