Evaluation of the efficacy and safety of tobramycin 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: 28 December 2015
• Main ID: EUCTR2009-016590-15-IT
• Date of registration: 14/03/2012
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: Evaluation of the efficacy and safety of tobramycin 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: 01/07/2011
• 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: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: Open label active if Pa positive culture at day29 If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Canada, France, Germany, Greece, Hungary, Italy, Poland, Russian Federation, Switzerland

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

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: 72
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 (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); 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

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Lung colonisation of Pseudomonas aeruginosa in cystic fibrosis patients.
MedDRA version: 14.1 Level: LLT Classification code 10021860 Term: Infection pseudomonas aeruginosa System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Trade Name: TOBI*NEBUL 56F 1D 300MG/5ML
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: TOBRAMYCIN
CAS Number: 32986-56-4
Current Sponsor code: NA
Other descriptive name: NA
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)

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

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.

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 Outcome(s)

Secondary end point(s): -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.

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

Secondary ID(s)

2009-016590-15-HU

CTBM100C2304

Source(s) of Monetary Support

NOVARTIS FARMA