A clinical trial to assess the treatment with nebulised tobramycin in terms of safety and ability to kill Pseudomonas bacteria in the lungs of cystic fibrosis patients aged 3 months to 6 years included

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2009-016590-15-PL
• Date of registration: 11/10/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A clinical trial to assess the treatment with nebulised tobramycin in terms of safety and ability to kill Pseudomonas bacteria in the lungs of cystic fibrosis patients aged 3 months to 6 years included
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Crossover Multi-Center Study to Assess the Efficacy and Safety of Inhaled Tobramycin Nebuliser Solution (TOBI®) for the Treatment of Early Infections of P. aeruginosa in Cystic Fibrosis Subjects Aged from 3 Months to less than 7 years.
• Date of first enrolment: 03/12/2013
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016590-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: Blinded cross-over only if negative Pa culture at day 29. Open label active if Pa positive culture If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Canada, Egypt, France, Germany, Greece, Hungary, Italy, Poland, Romania, Russian Federation, Switzerland, United States

Contacts

• Name: Novartis Pharma Services AG
• Affiliation: Clinical Trial Information Desk

• Name: Novartis Pharma Services AG
• Affiliation: Clinical Trial Information Desk

Key inclusion & exclusion 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:
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

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

Intervention(s)

Trade Name: TOBI 300 mg / 5 mL nebuliser solution
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Current Sponsor code: TBM100
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Proportion of patient P aeruginosa free at day 29.

Timepoint(s) of evaluation of this end point: Day 29

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

Secondary Outcome(s)

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.

Secondary ID(s)

2009-016590-15-HU

CTBM100C2304

Source(s) of Monetary Support

Novartis Pharma Services AG