Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   43206   clinical trials with a EudraCT protocol, of which   7151   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2015-002619-14
    Sponsor's Protocol Code Number:1199.36
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-05-17
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2015-002619-14
    A.3Full title of the trial
    A 24-week, double-blind, randomized, parallel-group study evaluating the efficacy and safety of oral nintedanib coadministrated with oral sildenafil, compared to treatment with nintedanib alone, in patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment
    Ensayo clínico doble ciego, aleatorizado, de grupos paralelos y de 24 semanas para evaluar la eficacia y seguridad de nintedanib oral administrado de forma concomitante con sildenafilo oral, en comparación con el tratamiento con nintedanib en monoterapia, en pacientes con fibrosis pulmonar idiopática (IPF) y afectación avanzada de la función pulmonar.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and safety of nintedanib when co-administered with sildenafil in IPF patients with advanced lung function impairment
    Eficacia y seguridad de nintedanib administrado de forma concomitante con sildenafilo en pacientes con IPF y afectación avanzada de la función pulmonar.
    A.4.1Sponsor's protocol code number1199.36
    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 SponsorBoehringer Ingelheim España, S.A.
    B.1.3.4CountrySpain
    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 supportBoehringer Ingelheim España, S.A.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBoehringer Ingelheim Pharma GmbH & Co. KG
    B.5.2Functional name of contact pointQRPE PSC CT Information Disclosure
    B.5.3 Address:
    B.5.3.1Street AddressBinger Strasse 173
    B.5.3.2Town/ cityIngelheim am Rhein
    B.5.3.3Post code55216
    B.5.3.4CountryGermany
    B.5.4Telephone number+34934045100
    B.5.5Fax number+34934045580
    B.5.6E-mailclintriage.rdg@boehringer-ingelheim.com
    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.2.1.1.1Trade name Ofev
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim International GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/3/13/1123
    D.3 Description of the IMP
    D.3.1Product nameOfev 100 mg capsule
    D.3.2Product code nintedanib
    D.3.4Pharmaceutical form Capsule, soft
    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 INNnintedanib
    D.3.9.3Other descriptive nameNINTEDANIB
    D.3.9.4EV Substance CodeSUB120728
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 2
    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.2.1.1.1Trade name Ofev
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim International GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/3/13/1123
    D.3 Description of the IMP
    D.3.1Product nameOfev 150 mg capsule
    D.3.2Product code nintedanib
    D.3.4Pharmaceutical form Capsule, soft
    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 INNnintedanib
    D.3.9.3Other descriptive nameNINTEDANIB
    D.3.9.4EV Substance CodeSUB120728
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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.2.1.1.1Trade name Revatio
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.1Product nameRevatio 20 mg
    D.3.2Product code sildenafil
    D.3.4Pharmaceutical form Capsule, hard
    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 INNSILDENAFIL
    D.3.9.1CAS number 139755-83-2
    D.3.9.3Other descriptive namesildenafil
    D.3.9.4EV Substance CodeSUB10517MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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 placeboCapsule, hard
    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
    patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment
    Pacientes con fibrosis pulmonar idiopática (IPF) y afectación avanzada de la función pulmonar
    E.1.1.1Medical condition in easily understood language
    Idiopathic pulmonary fibrosis
    Fibrosis pulmonar idiopática
    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 19.0
    E.1.2Level PT
    E.1.2Classification code 10021240
    E.1.2Term Idiopathic pulmonary fibrosis
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in IPF patients with advanced lung function impairment.
    Evaluar la eficacia y la seguridad del tratamiento concomitante con nintedanib y sildenafilo en pacientes con IPF y afectación avanzada de la función pulmonar.
    E.2.2Secondary objectives of the trial
    To enlarge the existing nintedanib mono-therapy database with safety and tolerability data in this population.
    Ampliar la base de datos existente de nintedanib en monoterapia con datos de seguridad y tolerabilidad en esta población
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent consistent with ICH-GCP and local laws, signed prior to any study procedures being performed (including any required washout);
    2. Male or female patients aged ?40 years at visit 1;
    3. A clinical diagnosis of IPF within the last 6 years before visit 1, based upon the ATS/ERS/JRS/ALAT 2011 guideline;
    4. Combination of high-resolution computed tomography (HRCT) pattern, and if available, surgical lung biopsy pattern consistent with a diagnosis of IPF as assessed by the investigator based on a HRCT scan performed within 18 months of visit 1;
    5. DLCO (corrected for Hb) ? 35% predicted of normal at visit 1.
    1.Consentimiento informado por escrito en consonancia con las normas de GCP de la ICH y con la legislación local, firmado antes de realizar cualquier procedimiento del estudio (incluido cualquier periodo de lavado).
    2.Varones o mujeres ?40 años en la visita 1.
    3.Diagnóstico clínico de IPF realizado en los 6 años previos antes de la visita 1, en función de las directrices ATS/ERS/JRS/ALAT 2011 [P11-07084].
    4.Combinación de patrón de tomografía computarizada de alta resolución (HRCT), y si está disponible, patrón de biopsia pulmonar quirúrgica, compatibles con un diagnóstico de IPF (véase el anexo 10.1), evaluado por el investigador en función de la HRCT realizada en los 18 meses previos a la visita 1.
    5.DLCO (corregida en función de Hb) ? 35 % del valor de referencia normal en la visita 1.
    E.4Principal exclusion criteria
    1. Previous enrolment in this trial;
    2. ALT, AST > 1.5 fold upper limit of normal (ULN) at visit 1;
    3. Total bilirubin > 1.5 fold ULN at visit 1;
    4. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7 at visit 1);
    5. History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1;
    6. Bleeding Risk: - Known genetic predisposition to bleeding; - Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin, etc.) or high dose antiplatelet therapy; - History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1; - History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1; - International normalised ratio (INR) > 2 at visit 1; - Prothrombin time (PT) and activated partial thromboplastin time (aPTT) > 150% of institutional ULN at visit 1;
    7. Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;
    8. History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1;
    9. Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula at visit 1;
    10. Presence of aortic stenosis (AS) per investigator judgement at visit 1;
    11. Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25% per investigator judgement at visit 1;
    12. Presence of idiopathic hypertrophic subaortic stenosis (IHSS) per investigator judgement at visit 1; 13. Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG) per investigator judgement at visit 1;
    14. Hypotension (systolic blood pressure [SBP] < 100 mm Hg or diastolic blood pressure [DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1;
    15. Uncontrolled systemic hypertension (SBP > 180 mmHg; DBP > 100 mmHg) at visit 1;
    16. Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose to priapism;
    17. Retinitis pigmentosa;
    18. History of vision loss;
    19. History of nonarteritic ischemic optic neuropathy;
    20. Veno-occlusive disease;
    21. History of acute IPF exacerbation or respiratory infection within 8 weeks of visit 2.
    22. Treatment with nitrates, n-acetylcysteine, pirfenidone, azathioprine, cyclophosphamide, cyclosporine, prednisone >15 mg daily or >30 mg every 2 days OR equivalent dose of other oral corticosteroids as well as any investigational drug within 4 weeks of visit 2;
    23. Treatment for pulmonary hypertension with prostaglandins (e.g., epoprostenol, treprostinil), endothelin-1 antagonists (e.g., bosentan, sitaxsentan, ambrisentan), phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) or a stimulator of guanylatcyclase (e.g., riociguat) within 4 weeks of visit 2;
    24. Treatment with potent CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir within 4 weeks of visit 2;
    25. Supplementation with L-arginine and concurrent use of grapefruit juice or St John's wort within 4 weeks of visit 2;
    26. Treatment with the reduced dose of nintedanib (100 mg bid) within 4 weeks of visit 2;
    27. Permanent discontinuation of nintedanib in the past due to adverse events considered drug-related;
    28. Known hypersensitivity or intolerance to nintedanib, sildenafil, galactose, peanut or soya or any other components of the study medication;
    29. A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial;
    30. Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment;
    31. Women who are pregnant, nursing, or who plan to become pregnant while in the trial;
    32.Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly;
    33.Patients not able to understand and follow study procedures including completion of self-administered questionnaires without help.
    34.Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment)
    1.Inclusión previa en este estudio.
    2.ALT, AST > 1,5 veces el límite superior de la normalidad (ULN) en la visita 1.
    3.Bilirrubina total > 1,5 veces el ULN en la visita 1.
    4.Obstrucción de las vías respiratorias relevantes (es decir, FEV1/FVC < 0,7 antes de la broncodilatación) en la visita 1.
    5.Antecedentes de infarto de miocardio en los 6 meses previos a la visita 1 o angina de pecho inestable durante el mes previo a la visita 1.
    6.Riesgo de hemorragia:
    -Predisposición hemorrágica genética conocida.
    -Pacientes que requieren fibrinólisis, dosis completa de tratamiento terapéutico anticoagulante (p. ej., antagonistas de la vitamina K, inhibidores directos de la trombina, heparina, hirudina, etc.) o un tratamiento antiagregante plaquetario en dosis altas.
    -Antecedentes de un episodio hemorrágico del sistema nervioso central (CNS) en los 12 meses previos a la visita 1.
    -Antecedentes de hemoptisis o hematuria, hemorragia gastrointestinal activa o úlceras y/o lesión grave o cirugía en los 3 meses anteriores a la visita 1.
    -Cociente internacional normalizado (INR) > 2 en la visita 1.
    -Tiempo de protrombina (PT) y tiempo de tromboplastina parcial (PTT) > 150 % el ULN en la visita 1.
    7.Cirugía mayor programada durante la participación el estudio, incluyendo trasplante pulmonar, cirugía abdominal o intestinal mayores.
    8.Antecedentes de episodio trombótico (incluido ictus y accidente isquémico transitorio) en los 12 meses previos a la visita 1.
    9.Aclaramiento de creatinina < 30 ml/min calculado según la fórmula de Cockcroft?Gault (anexo 10.2) en la visita 1.
    10.Presencia de estenosis aórtica (AS) según criterio del investigador en la visita 1.
    11.Insuficiencia cardíaca crónica grave: definida como fracción de eyección (EF) ventricular izquierda < 25 % según el criterio del investigador en la visita 1.
    12.Presencia de estenosis subaórtica hipertrófica idiopática (IHSS) según criterio del investigador en la visita 1.
    13.Bloqueo auriculoventricular (AV) de segundo o tercer grado en el electrocardiograma (ECG) según criterio del investigador en la visita 1.
    14.Hipotensión (presión arterial sistólica [SBP] < 100 mm Hg o presión arterial diastólica [DBP] < 50 mm Hg) (hipotensión ortostática sintomática) en la visita 1.
    15.Hipertensión sistémica no controlada (SBP > 180 mm Hg; DBP > 100 mm Hg) en la visita 1.
    16.Diagnóstico de deformidades o problemas en el pene (p. ej., anemia drepanocítica, mieloma múltiple, leucemia) que pueden predisponer a priapismo.
    17.Retinitis pigmentaria.
    18.Antecedentes de pérdida de visión.
    19.Antecedentes de neuropatía óptica isquémica no arterítica.
    20.Enfermedad venooclusiva.
    21.Antecedentes de reagudización de la IPF o infección respiratoria en las 8 semanas previas a la visita 2.
    22.Tratamiento con nitrato, n-acetilcisteína, pirfenidona, azatioprina, ciclofosfamida, ciclosporina o prednisona > 15 mg al día o > 30 mg cada 2 días O dosis equivalente de otro corticosteroide oral, así como cualquier fármaco en fase de investigación en las 4 semanas previas a la visita 2.
    23.Tratamiento para la hipertensión pulmonar con prostaglandinas (p. ej., epoprostenol, treprostinilo), antagonistas de la endotelina-1 (p. ej., bosentán, sitaxentán, ambrisentán), inhibidores de la fosfodiesterasa (p. ej., sildenafilo, tadalafilo, vardenafilo) o un estimulador de la guanilato ciclasa (p. ej., riociguat) en las 4 semanas anteriores a la visita 2.
    24.Tratamiento con inhibidores potentes del CYP3A4, como ketoconazol, itraconazol y ritonavir, en las 4 semanas anteriores a la visita 2.
    25.Suplemento con L-arginina y uso concurrente de zumo de pomelo o hierba de San Juan en las 4 semanas anteriores a la visita 2.
    26.Tratamiento con una dosis reducida de nintedanib (100 mg dos veces al día) en las 4 semanas anteriores a la visita 2.
    27.Suspensión permanente del tratamiento con nintedanib en el pasado debido a acontecimientos adversos considerados como relacionados con el fármaco.
    28.Pacientes con hipersensibilidad conocida o intolerancia a nintedanib, sildenafilo, galactosa, cacahuete, soja o cualquier componente de la medicación del estudio.
    29.Enfermedad o afección que, en opinión del investigador, pueda interferir con los procedimientos del estudio o poner al paciente en riesgo .
    30.Alcoholismo o toxicomanía que, en opinión del médico encargado del tratamiento, podrían interferir con el tratamiento.
    31.Mujeres embarazadas, en periodo de lactancia o que prevean quedarse embarazadas durante el periodo del estudio.
    32.Las mujeres potencialmente fértiles que no quieran o no puedan utilizar métodos anticonceptivos altamente eficaces según la directriz M3(R2) de la ICH, es decir, aquellos con una tasa de fracaso baja, inferior al 1 %, cuando se utilizan correctamente y de forma sistemática.
    33.Pacientes que no pueden comprender y seguir los procedimientos del estudio.
    34.Pacientes con enfermedad hepática crónica subyacente (daño hepático A, B o C según Child Pugh).
    E.5 End points
    E.5.1Primary end point(s)
    1: change from baseline in SGRQ total score at week 12
    1: Cambio respecto al periodo basal en la puntuación total del cuestionario SGRQ en la semana 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1: week 12
    1: semana 12
    E.5.2Secondary end point(s)
    1: change from baseline in UCSD SOBQ at week 12

    2: change from baseline in SGRQ total score at week 24

    3: change from baseline in UCSD SOBQ at week 24

    4: % of patients with on-treatment SAE from baseline to week 24
    1-Cambio respecto al periodo basal en la disnea usando el cuestionario UCSD SOBQ en la semana 12.

    2-Cambio respecto al periodo basal en la puntuación total del cuestionario SGRQ en la semana 24.

    3-Cambio respecto al periodo basal en la disnea usando el cuestionario UCSD SOBQ en la semana 24.

    4- Porcentaje de pacientes con SAE durante el tratamiento desde el periodo basal hasta la semana 24.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1: week 12

    2: week 24

    3: week 24

    4: week 24
    1: semana 12
    2: semana 24
    3: semana 24
    4: semana 24
    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 Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarkers
    Biomarcadores
    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.7.1.3.1Other 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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA41
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Canada
    China
    France
    Germany
    India
    Italy
    Japan
    Korea, Republic of
    Mexico
    Spain
    United Kingdom
    United States
    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
    LVLS
    Última visita del último paciente
    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 months10
    E.8.9.1In the Member State concerned days13
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days13
    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.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 300
    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)
    Patients will be treated according to clinical practice
    Los pacientes se tratarán de acuerdo a la práctica clínica
    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 Decision2016-06-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-04-13
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA