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    The EU Clinical Trials Register currently displays   43976   clinical trials with a EudraCT protocol, of which   7312   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    EudraCT Number:2014-001401-41
    Sponsor's Protocol Code Number:TAPAS-2014
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2014-05-15
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-001401-41
    A.3Full title of the trial
    Targeting Antibiotics to Pseudomonas Aeruginosa in Small airways (TAPAS) study in patients with cystic fibrosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Once daily deep inhalation of tobramycin with smart nebulizer more effective to treat small airways disease in cystic fibrosis?
    Eén maal daags diepe inhalatie van tobramycine met slimme vernevelaar effectiever voor behandeling van kleine luchtwegen bij cystic fibrosis?
    Una volta al giorno profonda inalazione di tobramicina connebulizzatore intelligente piu’ efficace per il trattamento delle piccole vie aeree in fibrosi cistica?
    A.3.2Name or abbreviated title of the trial where available
    TAPAS study in patients with CF
    A.4.1Sponsor's protocol code numberTAPAS-2014
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D. name Bramitob 300mg/4ml Nebuliser Solution
    D. of the Marketing Authorisation holderChiesi Limited
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/09/613
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Nebulisation solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cystic Fibrosis and chronic infection with Pseudomonas aeruginosa
    E.1.1.1Medical condition in easily understood language
    Mucoviscidosis and chronic lung infection
    Taaislijmziekte en chronische long infectie
    Fibrosi cistica e l'infezione polmonare cronica
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the change in small airways obstruction (FEF75%) in patients with CF when inhaling one ampule of inhaled tobramycin with the Akita® compared to standard of treatment (twice daily nebulization of one ampule using standard nebulizer equipment)
    E.2.2Secondary objectives of the trial
    1. To compare changes in lung function parameters (FEV1, FVC, FEF25-75%, MMEF25-75) and LCI.
    2. To compare changes in bacterial CFUs of Pseudomonas aeruginosa in sputum between both treatment arms.
    3. To compare the effect on ‘trapped air’ between both treatment arms as depicted by spirometer controlled expiratory chest Magnetic Resonance Imaging (MRI).
    4. To assess safety of Akita® tobramycin inhalation therapy in CF-patients by monitoring trough levels of tobramycine, ototoxicity and nephrotoxicity.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    1. Efficacy sub-study, objective: To compare the effect on ‘trapped air’ between both treatment arms as depicted by spirometer controlled expiratory chest Magnetic Resonance Imaging (MRI).
    2. Safety sub-study, objective: To assess safety of Akita® tobramycin inhalation therapy in CF-patients by monitoring ototoxicity.
    Date: april 2014, version 1.0
    E.3Principal inclusion criteria
    • Age ≥ 12 years
    • Clinical diagnosis of CF and a positive sweat test or two CF-related mutations;
    • Chronic Pa colonization requiring maintenance therapy with inhaled tobramycin, defined according to the Leeds criteria (>50% Pa positive airway cultures over last 12 months) 22;
    • Small airways obstruction present on spirometry (defined as follows: dissociation between FVC and FEF75 values (i.e. FEF75 at least 20% (absolute percent predicted) less than FVC);
    • Ability to breathe through a mouthpiece and to use the inhaler;
    • Ability to perform lung function tests;
    • Written informed consent (12-18 years: child and parents; ≥ 18 years: patient).
    E.4Principal exclusion criteria
    • Severe acute exacerbation of pulmonary infection (needing intravenous treatment) within one month prior to start or during the study;
    • Known impaired kidney function (estimated creatinine clearance < 60 ml/min);
    • Known aminoglycoside hypersensitivity;
    • Start of nephrotoxic or ototoxic drugs, e.g. aminoglycosides, within 1 month prior to start or during the study;
    • Therapy (e.g. furosemide) or disease which may complicate evaluation of the study protocol, as judged by the investigator;
    • Participation in another drug-investigating clinical study at the start or within 1 month prior to the start;
    • Inability to follow instructions of the investigator.
    • Use of Tobramycin Inhalation Powder as part of the maintenance therapy
    E.5 End points
    E.5.1Primary end point(s)
    change in FEF75 (Z-score and L/s) after 4 weeks of targeted treatment
    E.5.1.1Timepoint(s) of evaluation of this end point
    Every study visit. Patients will be included in the study for three months and study visits are planned at the start and end of the first and third month. 4 study visits in total.
    E.5.2Secondary end point(s)
    • Change in FEV1, FVC, FEF25, FEF50, MMEF25-75 (Z-scores and absolute values);
    • Change in Lung Clearance Index (LCI) measurements as assessed by multiple breath washout;
    • Change in Pa bacterial CFUs (defined as the log10 value for the number of Pa CFUs per millilitre of sputum, either expectorated or collected by suction of the oropharynx);
    • Change in percentage of trapped air on MRI (% of total lung volume);
    • Change in FEV1 before and after nebulisation (safety parameter);
    • Systemic bioavailability of inhaled tobramycin, defined by trough level;
    • Change in creatinine and blood urea nitrogen (BUN) values as measure of early renal toxicity;
    • Change in hearing function (measured by HFPTA);
    • Compliance rate;
    • Patient satisfaction (use of device);
    • Cystic Fibrosis questionnaire-revised (CFQ-R): respiratory symptoms scale scores and treatment burden scale scores.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At every study visit the following measurements will be performed:
    • Lung clearance index
    • Spirometry
    • MRI (subgroup of patients)
    • Sputum sample
    • Blood sample

    Evaluation of other endpoints:
    - trough level: end of first and third month (study visit 2 and 4)
    - Hearing function: start and end of first month, end of third month (study visit 1,2 and 4)
    - Compliance rate: end of first and third month (study visit 2 and 4)
    - Patient satisfaction: end of first and third month (study visit 2 and 4)
    - CFQ-R: end of first and third month (study visit 2 and 4)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E. description
    standard of treatment (twice daily nebulization of 300 mg tobramycin using standard nebulizer)
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA2
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial 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.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 13
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F. of subjects for this age range: 13
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 13
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 26
    F.4.2.2In the whole clinical trial 26
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-05-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-07-29
    P. End of Trial
    P.End of Trial StatusOngoing
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