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: 19 March 2012
• Main ID: EUCTR2006-006215-68-HU
• Date of registration: 25/06/2008
• 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: 13/08/2008
• 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

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).

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).



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)

Secondary Objective: Assess the efficacy of Tobrineb/Actitob®/ Bramitob® compared to TOBI® in the following secondary efficacy parameters: other pulmonary function tests(FEV1 % predicted measure at V(visit)3 & V5, FEV1 expressed as litres, Forced Vital Capacity [FVC]as litres& % predicted, Forced Expiratory Flow at 25-75% of Vital capacity [FEF25-75%]as litres/sec and % predicted measured at V3, V4 & V5). And the categorical results of microbiological tests(negative or positive culture, superinfection, re-infection) referred to P. aeruginosa; sputum culture, MIC50 and MIC90 of P. aeruginosa isolated strains; P.aeruginosa bacterial load(CFUs) performed at V4(end of treatment phase) & V5(end of follow up visit); and change in BMI.
Assess the safety of Tobrineb/Actitob®/ Bramitob® compared to TOBI® in the following safety parameters: adverse events & adverse drug reactions, audiometric tests, laboratory parameters(haematology & blood chemistry), vital signs(heart rate & blood pressure), physical examination.

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 ID(s)

2006-006215-68-CZ

CMA-0631-PR-0010