A Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI®
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: tobramycin / Bramitob; tobramycin / TOBI
Intervention description: 300mg/4ml solution, via a nebuliser, over a 4-week treatment in a twice-daily regimen; 300mg/5ml solution administered via nebuliser, over a 4-week treatment in a twice-daily regimen
Intervention MeSH terms: Tobramycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 324.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: cystic fibrosis; P. aeruginosa; tobramycin

Summary:

      The objectives of the study are to demonstrate that Tobrineb®/Actitob®/Bramitob® is
      non-inferior to TOBI® in the primary efficacy variable, forced expiratory volume in one
      second (FEV1) percent of predicted normal, and to compare the safety in participants with
      cystic fibrosis and chronic infection of the lungs with Pseudomonas aeruginosa.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients of either sex aged ≥ 6;

          -  Clinical diagnosis of cystic fibrosis defined as: (1)Patients preferably registered in
             the National Registry of CF (or other documents depending on country legislation); (2)
             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;

          -  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;

          -  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;

          -  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;

          -  Forced expiratory volume in 1 sec (FEV₁) ≥ 40% and ≤ 80% of the predicted normal
             value;

          -  Written informed consent obtained by parents/legal representative according to local
             regulations) and by the patient (when appropriate).

        Exclusion Criteria:

          -  Administration of antipseudomonal antibiotic therapy by any route in the previous 4
             weeks;

          -  Evidence of impaired renal function (serum creatinine level ≥ 1.5 mg/dl);

          -  Evidence of impaired auditory function (auditory threshold in either ear above 20 dB
             at frequencies between 250 and 8000Hz);

          -  Sputum culture containing Burkholderia cepacia;

          -  Patients with end-stage lung disease, candidates for heart-lung transplantation;

          -  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;

          -  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 intrauterine devices (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;

          -  Known hypersensitivity to aminoglycosides;

          -  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;

          -  Participation in another clinical trial with an investigational drug in the four weeks
             preceding the screening visit.