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    The EU Clinical Trials Register currently displays   37571   clinical trials with a EudraCT protocol, of which   6160   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2010-019685-87
    Sponsor's Protocol Code Number:RO-2455-404-RD
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-09-21
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2010-019685-87
    A.3Full title of the trial
    Effect of roflumilast on exacerbation rate in patients with COPD treated with fixed combinations of LABA and ICS. A 52-week, randomised double-blind trial with roflumilast 500 μg versus placebo
    Effetto di roflumilast sul tasso di esacerbazione in pazienti con COPD trattati con combinazioni fisse di LABA e ICS. Studio in doppio cieco, randomizzato, di 52 settimane con Roflumilast 500 μg verso placebo
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberRO-2455-404-RD
    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.1.1Name of SponsorNycomed GmbH
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 DAXAS
    D. of the Marketing Authorisation holderNycomed GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRoflumilast
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.3Concentration number500
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Severe chronic obstructive pulmonary disease (COPD)
    Malattia polmonare ostruttiva cronica (COPD) grave
    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 14.0
    E.1.2Level LLT
    E.1.2Classification code 10010952
    E.1.2Term COPD
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the effect of roflumilast 500 μg tablets once daily versus placebo on exacerbation rate and pulmonary function in COPD patients who are concomitantly treated with a fixed combination of LABA and ICS • To obtain data on safety and tolerability of roflumilast in COPD patients concomitantly treated with a fixed combination of LABA and ICS • To further characterise the population pharmacokinetic profile of roflumilast and roflumilast N-oxide • To further characterise the PK/PD relationship of roflumilast, roflumilast N-oxide and tPDE4i activity in terms of efficacy and relevant safety aspects
    • Studiare l'effetto di Roflumilast 500 µg in compresse somministrate una volta al giorno rispetto al placebo sul tasso di esacerbazione e sulla funzionalita' polmonare in pazienti con malattia polmonare ostruttiva cronica trattati contemporaneamente con una combinazione fissa di β2-agonisti a lunga durata d’azione (LABA, long-acting β2-agonists) e glucocorticosteroidi per via inalatoria (ICS, inhaled glucocorticosteroids). • Ottenere dati sulla sicurezza e la tollerabilita' di Roflumilast in pazienti con malattia polmonare ostruttiva cronica trattati con una combinazione fissa di LABA e ICS. • Caratterizzare ulteriormente il profilo farmacocinetico della popolazione di Roflumilast e Roflumilast N-ossido • Caratterizzare ulteriormente la relazione farmacocinetica/farmacodinamica (PK /PD) di Roflumilast, Roflumilast N-ossido e l'attivita' 'totale inibitoria della fosfodiesterasi 4' (tPDE4i) in termini di efficacia e di aspetti di sicurezza rilevanti.
    E.2.2Secondary objectives of the trial
    Please refer to ''Main objective'' section
    Fare riferimento alla sezione ''Obiettivo principale''
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Giving written informed consent 2. History of COPD (according to GOLD 2009) for at least 12 months prior to baseline Visit V0 associated with chronic productive cough for 3 months in each of the 2 years prior to baseline Visit V0 (with other causes of productive cough excluded) 3. Age ≥ 40 years 4. Forced expiratory volume after one second (FEV1)/forced vital capacity (FVC) ratio (post-bronchodilator) < 70% 5. FEV1 (post-bronchodilator) ≤ 50% of predicted 6. At least two documented moderate or severe COPD exacerbations,separated by at least 10 days, within one year prior to baseline Visit V0 7. Patients must be pre-treated with fixed combinations of LABA and ICS at a constant dose (maximum approved dosage strength of the combination) for at least 12 months prior to baseline Visit V0 separated by at least 10 days, within one year prior to baseline Visit V0 8. Former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 20 pack years.
    1.I pazienti forniscono il consenso informato scritto 2.Anamnesi di COPD (secondo GOLD 2009)per almeno 12 mesi prima della Visita basale V0 associata a tosse cronica produttiva per 3 mesi in ciascuno dei 2 anni precedenti alla Visita basale V0 (con l'esclusione di altre cause della tosse produttiva) 3.Eta' ≥ 40 anni 4.Rapporto Volume espiratorio forzato dopo un secondo (FEV 1)/capacita' vitale forzata (FVC, forced vital capacity), (post-broncodilatatore) &lt; 70% 5.FEV 1 (post-broncodilatatore) ≤50% del previsto 6.Almeno due esacerbazioni documentate della COPD moderate o gravi , separate da almeno 10 giorni, nell’anno precedente la visita basale V0 7.I pazienti devono essere pre-trattati con combinazioni fisse di LABA e ICS ad un dosaggio costante (al dosaggio massimo approvato per la combinazione) per almeno 12 mesi prima della visita basale V0 8.Ex fumatore (definito come la cessazione dell'abitudine al fumo di almeno un anno prima) o fumatore corrente entrambi che fumino o abbiano fumato almeno 20 sigarette al giorno per un anno
    E.4Principal exclusion criteria
    1. Moderate or severe COPD exacerbation and/or COPD exacerbations treated with antibiotics ongoing at the baseline Visit V0 2. Lower respiratory tract infection not resolved 4 weeks prior to the baseline Visit V0 3. Diagnosis of asthma and/or other relevant lung disease (e.g. history of primary bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], or active tuberculosis) 4. Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the baseline Visit V0 5. Known alpha-1-antitrypsin deficiency Clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the Investigator) 7. Severe psychiatric or neurological disorders 8. History of depression associated with suicidal ideation or behaviour 9. Congestive heart failure severity grade IV according to NYHA (New York Heart Association Functional Classification) 10. Haemodynamically significant cardiac arrhythmias or heart valve deformations 11. Computed tomography (CT) or chest x-ray findings indicating an acute pulmonary disease other than COPD (e.g. tuberculosis, severe bronchiectasis, tumours) 12. Severe immunological diseases (e.g. known HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy) 13. Liver impairment Child-Pugh B or C and/or active viral hepatitis 14. Severe acute infectious diseases (e.g. tuberculosis, or acute hepatitis) 15. Any diagnosis of a malignant disease (except basal cell carcinoma) within 5 years before trial start 16. Alcohol or drug abuse within the past year 17. Suspected hypersensitivity to roflumilast or rescue medication or ingredients thereof, or any other contraindication for the use thereof 18. Female patients of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire trial duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, unless they are surgically sterilized/hysterectomised or post-menopausal > 1 year or who are not using any other method of contraception considered sufficiently reliable by the Investigator in individual cases 19. Pregnancy, breast feeding, planned oocyte donation or oocyte implantation 20. Planned donation of germ cells, blood, organs or bone marrow during the course of the trial 21. Participation in another trial (use of investigational product) within 30 days preceding the baseline Visit V0 or re-entry of patients previously enrolled in this trial 22. Suspected inability or unwillingness to comply with trial procedures (e.g. language problems, psychological disorders, number and timing of visits at the site) Suffering from any concomitant disease that might interfere with trial procedures or evaluations 24. Use of disallowed drugs (see below) 25. Employee at the investigational site, relative or spouse of the Investigator
    1.Esacerbazione della COPD, moderata o grave, e/o esacerbazione della COPD trattata con antibiotici in corso alla visita basale V0 2.Infezione del tratto respiratorio inferiore non risolta 4 settimane prima della Visita basale V0 3.Diagnosi di asma e/o altre malattie polmonari pertinenti (ad esempio anamnesi di bronchiolectasie primarie, fibrosi cistica, bronchiolite, resezione polmonare, tumore polmonare, malattia polmonare interstiziale [ad esempio fibrosi, silicosi, sarcoidosi], o tubercolosi attiva) 4.Attuale partecipazione ad un programma di riabilitazione polmonare o completamento di un programma di riabilitazione polmonare nei 3 mesi precedenti la Visita basale V0 5.Noto deficit di alfa 1-antitripsina 6.Valori di laboratorio anormali clinicamente significativi che indicano una malattia non diagnosticata che richiede ulteriore valutazione clinica (come valutato dallo sperimentatore) 7.Gravi disturbi psichiatrici o neurologici 8.Anamnesi di depressione associata a ideazione o comportamento suicida 9.Insufficienza cardiaca congestizia di gravita' corrispondente al grado IV secondo NYHA (New York Heart Association Functional Classification) 10.Aritmie cardiache emodinamicamente significative o deformazioni della valvola cardiaca 11.Tomografia computerizzata (TC) del torace o esiti alla radiografia toracica che suggeriscano una malattia polmonare acuta diversa dalla COPD (ad esempio tubercolosi, bronchiettasia grave, tumori) 12.Gravi malattie immunologiche (es. nota infezione da HIV, sclerosi multipla, lupus eritematoso, leucoencefalopatia multifocale progressiva) 13.Insufficienza epatica Child-Pugh B o C e/o epatite virale attiva 14.Gravi malattie infettive acute (ad esempio tubercolosi, o epatite acuta) 15.Ogni diagnosi di malattia maligna (eccetto carcinoma a cellule basali) entro 5 anni prima dell'inizio dello studio 16.L'abuso di alcol o droga nel corso dell'ultimo anno 17.Sospetta ipersensibilita' a Roflumilast o al farmaco di supporto o ai suoi componenti, o qualsiasi altra controindicazione per il loro uso 18.Le pazienti in eta' fertile che non usano e non sono disposte a continuare ad usare un metodo contraccettivo affidabile a livello medico per la durata dell'intero studio, come contraccettivi orali, iniettabili o impiantabili o dispositivi contraccettivi intrauterini, se non sono sterilizzate chirurgicamente/con isteroctomia o post-menopausa &gt; 1 anno o che non stanno utilizzando qualsiasi altro metodo di contraccezione considerato sufficientemente affidabile dallo sperimentatore nei singoli casi 19.Gravidanza, allattamento, programmata donazione di ovociti o impianto di ovociti 20.Donazione programmata di cellule germinali, sangue, organi o di midollo osseo nel corso dello studio 21.La partecipazione ad un altro studio (uso di prodotto sperimentale) entro i 30 giorni precedenti alla visita basale V0 o la reintroduzione di pazienti precedentemente arruolati in questo studio 22.Sospetta incapacita' o non volonta' di rispettare le procedure della sperimentazione (ad esempio problemi di lingua, disturbi psicologici, numero e tempistica delle visite al centro) 23.L'essere affetti da malattie concomitanti che potrebbero interferire con le procedure o le valutazioni dello studio 24.L'uso di farmaci non consentiti (vedi sotto) 25.Persona impiegata presso il centro di sperimentazione, parente o coniuge dello Sperimentatore
    E.5 End points
    E.5.1Primary end point(s)
    • Rate of moderate or severe COPD exacerbations per patient per year. Moderate exacerbations are defined as requiring oral or parenteral glucocorticosteroids, severe as requiring hospitalisation and/or leading to death
    • Frequenza di esacerbazioni della COPD moderate o gravi per paziente all'anno. Le esacerbazioni moderate sono quelle che richiedono glucocorticosteroidi per via orale o parenterale, e gravi quelle che richiedono il ricovero in ospedale e/o causano il decesso
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA95
    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 No
    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
    Il protocollo identifica la chiusura del database quale data di conclusione della sperimentazione.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months32
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months32
    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 No
    F.1.1Number of subjects for this age range: 0
    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) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1475
    F.4.2.2In the whole clinical trial 3002
    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 Decision2011-06-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-05-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-07-30
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