E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cystic fibrosis and P. aeruginosa chronic infection |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057582 |
E.1.2 | Term | Lung infection pseudomonal |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011763 |
E.1.2 | Term | Cystic fibrosis lung |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
|
|
E.4 | Principal 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).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline of FEV1 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |