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.

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2009-016590-15-GR
• Date of registration: 31/12/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public 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.
• 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: 15/06/2010
• Target sample size: 72
• 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: yes Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: 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

Countries of recruitment

France, Germany, Greece, Hungary, Italy, Poland

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:
• infection defined as the first time P. aeruginosa is isolated from sputum or deep throat cough swab culture, or
• isolation of P. aeruginosa from sputum or deep-throat cough-swab culture 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), no
antipseudomonal treatment by any route of administration during this one-year
period;
5. Able to comply with all protocol requirements (except spirometry where not applicable)
6. Clinically stable in the opinion of the investigator.
Are the trial subjects under 18? yes
Number of subjects for this age range:
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. Serum creatinine above the upper limit of the normal range for age.
2. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
3. Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax.
4. Administration of any investigational drug within 30 days or 5 half-lives prior to
enrollment, whichever is longer.
5. Administration of loop diuretics within 7 days prior to study drug administration.
6. Personal/family history of abnormal hearing
7. Current (continuing, present at screening) or persisting abnormal result from audiology testing (as defined in protocol).
8. 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.
9. Hemoptysis which is clinically significant based on the subjects age and clinical status within 30 days prior to study drug administration.
10. History of malignancy of any organ system treated or untreated, regardless of whether there is evidence of local recurrence or metastases,
11. Subjects with clinically significant laboratory abnormalities including congenital diseases other than CF (not associated with the study indication) at screening,
12. Subjects with other clinically significant conditions (not associated with the study
indication) at screening which might interfere with the assessment of this study
13. 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

Lung colonisation of Pseudomonas aeruginosa in cystic fibrosis patients
MedDRA version: 12.0 Level: LLT Classification code 10068297 Term: Pseudomonas colonisation
MedDRA version: 12.0 Level: LLT Classification code 10068292 Term: Pseudomonas colonization

Intervention(s)

Trade Name: TOBI 300mg/5mL nebuliser solution
Product Name: TOBI
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: Tobramycin
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)

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.

Primary end point(s): Proportion of patients with negative P. aeruginosa culture at day 29 in each treatment group

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 ID(s)

CTBM100C2304

2009-016590-15-HU