Lung colonisation with Pseudomonas aeruginosa in cystic fibrosis patients MedDRA version: 14.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 14.1 Level: LLT Classification code 10068292 Term: Pseudomonas colonization System Organ Class: 100000004862 MedDRA version: 14.1 Level: LLT Classification code 10068297 Term: Pseudomonas colonisation System Organ Class: 100000004862
Conditions
Interventions
Trade Name: TOBI 300 mg / 5 mL nebuliser solution
Product Name: TOBI
Product Code: TBM100
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Current Sponsor
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent given by the parent/legal guardian on behalf of the subject. 2. Diagnosis of CF by one or more clinical features of CF: • a documented sweat chloride test of > 60 mEq/L by quantitative pilocarpine iontophoresis • genotype with two identifiable CF-causing mutations • a positive newborn screening for CF 3. Male and female subjects aged 3 months to less than 7 years of age at the time of screening. 4. Early lower respiratory tract infection with P. aeruginosa, defined by either of the following: a. The first time P. aeruginosa isolated b. P. aeruginosa isolated after at least 1 year of negative cultures (documented with at least two negative cultures during the latter 1-year period, with no positive culture during that period) 5. Positive P. aeruginosa culture isolated from sputum, deep throat swab or nasopharyngeal aspiration specimens collected and tested from routine clinical culture performed at local site laboratory within 1 months prior to randomization 6. Able to comply with all protocol requirements (except spirometry where not applicable) Clinically stable in the opinion of the investigator Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any oral or iv anti-pseudomonal antibiotic treatment within 1 year prior to randomization 2. Serum creatinine above the upper limit of the normal range for age documented from at least one analysis performed at site laboratory within 6 month prior to randomization 3. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics. 4. Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax. 5. Administration of any investigational drug within 30 days or 5 half-lives prior to enrollment, whichever is longer. 6. Administration of loop diuretics within 7 days prior to study drug administration. 7. Personal/family history of abnormal hearing 8. Current (continuing, present at screening) or persisting abnormal result from audiology testing (defined as either a unilateral pure-tone audiometry test showing a threshold elevation > 20 dB at any frequency across the frequency range 0.25 kHz to 8 kHz or the absence of emission at the evoked otoacoustic emission test). 9. History of sputum culture, throat swab, or lower respiratory specimen culture yielding Burkholderia cepacia (B. cepacia) within 2 years prior to screening and/or sputum culture yielding B. cepacia at screening. 10. Hemoptysis which is clinically significant based on the subjects age and clinical status within 30 days prior to study drug administration. 11. History of malignancy of any organ system treated or untreated, regardless of whether there is evidence of local recurrence or metastases, 12. Subjects with clinically significant laboratory abnormalities including congenital diseases other than CF (not associated with the study indication) documented from at least one laboratory chemistry and haematology analysis performed within 1 year prior to randomization 13. Subjects with other clinically significant conditions (not associated with the study indication) at screening which might interfere with the assessment of this study 14. Subjects or caregivers with a history of noncompliance to medical regimens and subjects or caregivers who are considered potentially unreliable.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the proportion of subjects free from any strain of P. aeruginosa assessed by sputum / swab culture at Day 29, i.e. after completion of a 28-day treatment period with either TOBI or placebo solution inhaled twice daily. ;Secondary Objective: • To assess the safety profile of TOBI inhaled twice daily or placebo throughout the treatment period in subjects in this age group. • To estimate the proportion of subjects free from any strain of P. aeruginosa assessed by sputum / swab culture 28 days after termination of the 2nd treatment cycle (day 91) with either TOBI inhaled twice daily for 28 days or placebo. • To estimate the proportion of subjects free from any strain of P. aeruginosa assessed by sputum / swab culture 28 days after termination of treatment with either TOBI inhaled twice daily for 28 days or placebo. • To assess the pharmacokinetics of TOBI in this age group • To assess lung function in the subset of subjects able to reliably perform spirometry ;Primary end point(s): Proportion of patient P aeruginosa free at day 29.;Timepoint(s) of evaluation of this end point: Day 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects with P. aeruginosa free 28 days after last study medication, • Proportion of subjects with P. aeruginosa free at day 91 (end of treatment phase) • Relative change in FEV1, FVC and FEF 25-75 (all values as % predicted) from baseline to final visit (end of treatment phase), at selected sites in subjects able to perform PFT.;Timepoint(s) of evaluation of this end point: Stated directly in endpoints description above. Please also refer to assessment schedule in full protocol. | — |
Countries
Canada, France, Germany, Greece, Hungary, Italy, Poland, Russian Federation, Switzerland
Contacts
Public ContactPublic Information Desk
Novartis Hungária Kft., Pharma
Outcome results
None listed