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    The EU Clinical Trials Register currently displays   43716   clinical trials with a EudraCT protocol, of which   7255   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:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2021-09-07
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    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
    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
    Targeting Antibiotics to Pseudomonas aeruginosa in Small airways study in patients with Cystic Fibrosis
    trattamento antibiotico dell’infezione cronica da Pseudomonas aeruginosa in pazienti con Fibrosi Cistica
    A.3.2Name or abbreviated title of the trial where available
    TAPAS study in patients with CF
    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
    B.Sponsor: 1
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support ERASMUS MC
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationErasmus MC- Sophia Children's Hospital
    B.5.2Functional name of contact pointPrincipal Investigator Netheralnds
    B.5.3 Address:
    B.5.3.1Street AddressWytemaweg 80, Sp 3456
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015CN
    B.5.4Telephone number+31107037980
    B.5.5Fax numberNA
    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. of the Marketing Authorisation holderCHIESI FARMACEUTICI S.P.A.
    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.3.1Product nameBramitob
    D.3.4Pharmaceutical form Nebuliser solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTOBRAMICINA
    D.3.9.1CAS number 32986-56-4
    D.3.9.2Current sponsor codeBRAMITOB
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 Information not present in EudraCT
    D. therapy medical product Information not present in EudraCT
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    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 aeuroginosa
    Fibrosi Cistica associata ad infezione cronica da Pseudomonas aeuroginosa
    E.1.1.1Medical condition in easily understood language
    Mucoviscidosis and crhonic lung infection
    Fibrosi cistica e infezione polmonare cronica
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 22.1
    E.1.2Level LLT
    E.1.2Classification code 10057582
    E.1.2Term Lung infection pseudomonal
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    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 300 mg of inhaled tobramycin with the Akita® compared to standard of treatment (twice daily nebulization of one ampule of 300 mg using standard nebulizer equipment)
    Confrontare il cambiamento di ostruzione delle piccole vie aeree (FEF75%) nei pazienti con fibrosi cistica trattati con una fiala di 300 mg di tobramicina per inalazione con Akita® rispetto al trattamento standard (nebulizzazione di una fiala da 300 mg con nebulizzatore standard due volte al giorno)
    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.
    1. confrontare alterazioni dei parametri di funzionalità polmonare (FEV1, FVC, FEF25-75%, MMEF25-75) e LCI.
    2. confrontare le modifiche in CFU di Pseudomonas aeruginosa nell'espettorato tra i due bracci di trattamento.
    3. confrontare gli effetti sull 'aria intrappolata su MRI tra i due bracci di trattamento.
    4. valutare la sicurezza della terapia inalatoria di tobramicina con Akita® nei pazienti con CF controllando i livelli di tobramicina, ototossicità e nefrotossicità.
    E.2.3Trial contains a sub-study No
    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).
    • Età = 12 anni
    • Diagnosi clinica di CF e un test del sudore positivo o due mutazioni CF-correlate;
    • colonizzazione Pa cronica che richiede una terapia di mantenimento con tobramicina per inalazione.
    • ostruzione delle piccole vie aeree evidenziata dalla spirometria
    • capacità di respirare attraverso un boccaglio e di utilizzare l'inalatore;
    • Capacità di eseguire test di funzionalità polmonare - spirometria-;
    • consenso informato scritto (12-18 anni: bambino e genitori; = 18 anni: paziente)
    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;
    •Use of Tobramycin Inhalation Powder as part of the maintenance therapy
    -Esacerbazione polmonare acuta grave (che necessita di un trattamento endovenoso) entro un mese prima di iniziare o durante lo studio;
    -Funzionerenale compromenssa(Clearance della creatinina minore 60ml/min;
    - ipersensibilità nota agli aminoglicosidi;
    uso di trbamicina in polvere come parte della terapia cronica;
    E.5 End points
    E.5.1Primary end point(s)
    change in FEF75 (Z-score and L/s) after 4 weeks of targeted treatment.
    variazione del valore di FEF75 (Z-score e L/s) dopo 4 settimane di trattamento mirato
    E.5.1.1Timepoint(s) of evaluation of this end point
    Every study visit. Patients will be included for 3 months and study visit are planned at the start and end of the first andthird month. 4 study visits in total
    Ogni visita dello studio. I pazienti saranno inclusi per 3 mesi e le visite per lo studio sono previste all'inizio e alla fine del primo e del terzo mese. 4 visite in totale
    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, 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.
    •Variazione del FEV1, FVC, FEF25, FEF50, MMEF25-75 (Z-scores e valori assoluti);; •Variazione del Lung Clearance Index (LCI) ; Variazioni Delle CFU batteriche; Variazione della percentuale di aria intrappolata su MRI (% del volume polmonare totale); -Variazione dei valori di FEV1, FVC, FEF25, FEF50, MMEF25-75 (Z-scores e valori assoluti);
    -Variazione dell'indice di Clearance polmonare (LCI);
    -Variazioni delle Unità formanti colonia batterica;
    -Variazione della percentuale di aria intrappolata in MRI (% delvolume polmonare totale);
    -Variazione del valore di FEV1 prima e dopo la nebulizzazione ( paramentro di sicurezza);
    -Biodisponibilità sistemica della tobramicina definita per via inalatoria;
    - Variazione della creatinina e dell'azoto urico nel sangue come misura della tossicità renale precoce;
    - Variazione dell'udito;
    -Grado di soddisfazione del paziente
    -Somministrazione del questionario (CFQ-R):
    E.5.2.1Timepoint(s) of evaluation of this end point
    4 weeks; 4 weeks; 4 weeks; 4 weeks; study visit 2 and 4
    4 settimane; 4 settimane; 4 settimane; 4 settimane; seconda e quarta visita per lo studio
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E. description
    trattamento standard ( nebulizzazione di 300 mg di trobamicina due volte al giorno con nebulizatore
    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.8.4.1Number of sites anticipated in Member State concerned1
    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 Information not present in EudraCT
    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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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 state20
    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 Decision2015-12-17
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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