A MULTICENTRE,MULTINATIONAL, OPEN-LABEL, RANDOMISED, PARALLEL GROUP CLINICAL TRIAL OF TOBRINEB®/ACTITOB®/ BRAMITOB® (TOBRAMYCIN SOLUTION FOR NEBULISATION, 300 MG TWICE DAILY IN 4 ML UNIT DOSE VIALS) COMPARED TO TOBI® IN THE TREATMENT OF PATIENTS WITH CYSTIC FIBROSIS AND CHRONIC INFECTION WITH PSEUDOMONAS AERUGINOSA

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2006-006215-68-FR
• Date of registration: 06/08/2009
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A
• Public title: A MULTICENTRE,MULTINATIONAL, OPEN-LABEL, RANDOMISED, PARALLEL GROUP CLINICAL TRIAL OF TOBRINEB®/ACTITOB®/ BRAMITOB® (TOBRAMYCIN SOLUTION FOR NEBULISATION, 300 MG TWICE DAILY IN 4 ML UNIT DOSE VIALS) COMPARED TO TOBI® IN THE TREATMENT OF PATIENTS WITH CYSTIC FIBROSIS AND CHRONIC INFECTION WITH PSEUDOMONAS AERUGINOSA
• Scientific title: A MULTICENTRE,MULTINATIONAL, OPEN-LABEL, RANDOMISED, PARALLEL GROUP CLINICAL TRIAL OF TOBRINEB®/ACTITOB®/ BRAMITOB® (TOBRAMYCIN SOLUTION FOR NEBULISATION, 300 MG TWICE DAILY IN 4 ML UNIT DOSE VIALS) COMPARED TO TOBI® IN THE TREATMENT OF PATIENTS WITH CYSTIC FIBROSIS AND CHRONIC INFECTION WITH PSEUDOMONAS AERUGINOSA
• Date of first enrolment: 21/09/2009
• Target sample size: 320
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006215-68
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Germany, Hungary, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients of either sex aged = 6; 2. Clinical diagnosis of cystic fibrosis defined as: • patients preferably registered in the National Registry of CF (or other documents depending on country legislation); • evidence of two or more typical pulmonary clinical features observed in CF e.g persistent colonization/infection with typical CF pathogens, chronic cough and sputum production, persistent chest radiography abnormalities, airway obstruction, nasal polyps and/or digital clubbing.; 3. Positive response in the standard sweat test (sweat chloride concentration = 60 mmol/l) for the standard method or = 80 mmol/L for a microduct technique) documented in the clinical records and/or gene mutation documented in the clinical records; 4. Chronic colonization of P. aeruginosa : presence in a sputum or throat culture of a minimum of 2 positive samples for P. aeruginosa over the previous 12 months and/or presence of more than two precipitating antibodies against P. aeruginosa; 5. Sputum containing P. aeruginosa susceptible to tobramycin (defined as a zone diameter = 16 mm after testing with 10 µg tobramycin disk or as a minimal inhibition concentration based on microdilution testing system) as identified by local laboratory at screening visit; 6. FEV1 = 40% and = 80% of the predicted normal value; 7. Written informed consent obtained by parents/legal representative (according to local regulations) and by the subject (when appropriate). 8. Patients who complete the first 8-week study period, have a positive culture for P. aeruginosa at visit 4 of the first 8-week study period and/or if deemed appropriate by the Investigators will be eligible to enter in a 48-week follow on period with Bramitob® only, provided that written informed consent is obtained for the follow-on study period.
Are the trial subjects under 18? yes
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:
1. Administration of antipseudomonal antibiotic therapy by any route in the previous 4 weeks 2. Evidence of impaired renal function (serum creatinine level = 1.5 mg/dl); 3. Evidence of impaired auditory function (auditory threshold in either ear above 20 dB at frequencies between 250 and 8000Hz); 4. Sputum culture containing Burkholderia cepacia; 5. Patients with end-stage lung disease, candidates for heart-lung transplantation; 6. History of other clinically significant cardiac, renal, neurological, gastrointestinal, hepatic or endocrine disease related to cystic fibrosis, whose sequelae and/or treatment can interfere with the results of the present study; 7. Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e. contraceptive methods other than rod containing a hormone that prevents user from getting pregnant and that will be placed under the skin, syringes that contain a contraceptive hormone, combined birth control pill i.e. such that contains two hormones, some IUDs and sexual abstinence). A pregnancy test in urine is to be carried out in women of a fertile age at screening and at the last clinic visit. 8. Known hypersensitivity to aminoglycosides; 9. Patients with evidence of alcohol or drug abuse, likely to be not compliant with the study protocol or likely to be not compliant with the study treatments; 10. Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit (Visit 1) and during the overall study period including the 48-week follow on period. 11. For France : patients covered by the articles L.1121-6 and L.1121-8 of the French Public Health Code and patients not affiliated to a social security system or covered by such a system.


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

Health Condition(s) or Problem(s) studied

cystic fibrosis and P. aeruginosa chronic infection
MedDRA version: 9.1 Level: LLT Classification code 10057582 Term: Lung infection pseudomonal
MedDRA version: 9.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung

Intervention(s)

Trade Name: Bramitob
Product Name: Tobrineb/Bramitob
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: tobramycin
CAS Number: as32986-56-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300mg-4ml

Trade Name: Tobi 300mg/5ml Nebuliser solution.
Product Name: Tobi
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: tobramycin
CAS Number: 49842-07-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300mg-5ml

Primary Outcome(s)

Main Objective: The primary objective of the study will be to demonstrate that Tobrineb/Actitob®/ Bramitob® is noninferior to TOBI® in primary efficacy variable forced expiratory volume in one second (FEV1) percent predicted in patients with CF and chronic infection of the lungs with P. aeruginosa.

Primary end point(s): Change from baseline of FEV1

Secondary Objective: Assess efficacy of Tobrineb/Actitob®/ Bramitob® compared to TOBI® in the following secondary efficacy parameters: other pulmonary function tests(see protocol p25), categorical results of microbiological tests(see protocol p25 for details); and change in BMI. Assess safety of Tobrineb/Actitob®/ Bramitob® compared to TOBI® in safety parameters defined p.25 of protocol. Main objectives of 48-week follow on period will be: - assess safety profile of patients chronically infected with P.aeruginosa receiving repeated, intermittent 28-day courses of tobramycin 300mg bid in a period of 12 months (see protocol p25 for details). - assess prolonged use aerosolised tobramycin required to sustain FEV1 increase; - assess tobramycin susceptibility of P.Aeruginosa strains in patients receiving 6 repeated, intermittent, 28-day courses of tobramycin 300mg bid; - assess nutritional status (determined by body weight and BMI); - assess Health Related Quality of Life.

Secondary ID(s)

2006-006215-68-CZ

CMA-0631-PR-0010

Ethics review

Status: Approved
Approval date: 21/09/2009
Contact:

Results

• Results available: Yes
• Date Posted: 09/07/2017
• Date Completed: 24/05/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-006215-68/results