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
Conditions
Interventions
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
Sponsors
Chiesi Farmaceutici S.p.A
Eligibility
Sex/Gender
All
Inclusion 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
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;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.;Primary end point(s): Change from baseline of FEV1 | — |
Countries
Czech Republic, France, Germany, Hungary, Spain
Outcome results
None listed