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    Summary
    EudraCT Number:2015-002046-31
    Sponsor's Protocol Code Number:KFL3503
    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:2016-02-03
    Trial 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 number2015-002046-31
    A.3Full title of the trial
    A randomised, single blind, cross-over study to compare a fixed dose combination of fluticasone propionate / formoterol fumarate (fluticasone /formoterol breath actuated inhaler (BAI)) with a fixed dose combination of indacaterol maleate / glycopyrronium bromide (Ultibro® Breezhaler) in subjects with fixed airflow obstruction and elevated eosinophils.
    Estudio aleatorizado, simple ciego, cruzado para comparar una combinación a dosis fija de fluticasona propionato/formoterol fumarato (inhalador activado por inspiración de fluticasona/formoterol) con una combinación a dosis fija de maleato de indicaterol/bromuro de glicopirronio (Ultibro® Breezhaler) en pacientes con obstrucción fija del flujo de aire y elevación de eosinófilos.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research study to compare two treatments for treating a respiratory disease known as asthma-COPD overlap syndrome (ACOS).
    Un estudio de investigación para comparar dos tratamientos para tratar una enfermedad respiratoria conocida como síndrome de solapamiento asma-EPOC (SSAE).
    A.4.1Sponsor's protocol code numberKFL3503
    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 SponsorMundipharma Research Limited
    B.1.3.4CountryUnited Kingdom
    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 supportMundipharma Research Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationScope International AG
    B.5.2Functional name of contact pointProject Management
    B.5.3 Address:
    B.5.3.1Street AddressKonrad-Zuse-Ring 18
    B.5.3.2Town/ cityMannheim
    B.5.3.3Post code68163
    B.5.3.4CountryGermany
    B.5.4Telephone number+496214293994
    B.5.5Fax number+496214293940
    B.5.6E-mailScope_KFL3503@scope-international.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 flutiform® 125 microgram / 5 microgram per actuation pressurised inhalation, suspension
    D.2.1.1.2Name of the Marketing Authorisation holderNapp Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameFluticasone/formoterol BAI 125/5 µg
    D.3.2Product code K-haler
    D.3.4Pharmaceutical form Pressurised inhalation, suspension
    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 INNfluticasone propionate
    D.3.9.1CAS number 80474-14-2
    D.3.9.3Other descriptive nameFLUTICASONE PROPIONATE
    D.3.9.4EV Substance CodeSUB02241MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN/ formoterol fumarate dihydrate
    D.3.9.3Other descriptive name/ FORMOTEROL FUMARATE DIHYDRATE
    D.3.9.4EV Substance CodeSUB25660
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 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 Ultibro® Breezhaler 85 micrograms/43 micrograms, inhalation powder hard capsules
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 Inhalation powder, hard capsule
    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 INNindacaterol maleate
    D.3.9.1CAS number 753498-25-8
    D.3.9.3Other descriptive nameINDACATEROL MALEATE
    D.3.9.4EV Substance CodeSUB30300
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number143
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN/ GLYCOPYRRONIUM BROMIDE
    D.3.9.1CAS number / 596-51-0
    D.3.9.4EV Substance CodeSUB07951MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number63
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Fixed airflow obstruction with elevated eosinophils
    Obstrucción crónica de las vías respiratorias con eosinófilos elevados.
    E.1.1.1Medical condition in easily understood language
    Long term breathing problems (combination of Asthma and Chronic Obstructive Pulmonary Disease) accompanied by inflammation of the lungs
    Problemas respiratorios a largo plazo (combinación de asma y enfermedad pulmonar obstructiva crónica) acompañados por inflamación de los pulmones
    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 18.1
    E.1.2Level LLT
    E.1.2Classification code 10077006
    E.1.2Term Asthma-COPD overlap syndrome
    E.1.2System Organ Class 100000004855
    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 efficacy of fluticasone /formoterol BAI 125/5 microgram (2 puffs b.i.d.) versus Ultibro Breezhaler 85/43 microgram (1 puff o.d.) in terms of the percentage of eosinophils in induced sputum at Week 6 of each treatment.
    Comparar la eficacia de fluticasona /formoterol inhalador activado por la inspiración 125/5 microgram (2 inhalaciones 2 v/d) con Ultibro Breezhaler 85/43 microgram (1 inhalación 1 v/d) en cuanto al porcentaje de eosinófilos presentes en esputo inducido en la semana 6 de cada tratamiento.
    E.2.2Secondary objectives of the trial
    Key Secondary Objective:
    To compare the efficacy of fluticasone /formoterol BAI 125/5 microgram (2 puffs b.i.d.) versus Ultibro Breezhaler 85/43 microgram (1 puff o.d.) in terms of the serum concentration of SPD at Week 6 of each treatment.

    Only the Key Secondary Objective is listed here.
    Please refer to section 7.3 of the protocol (Final Version 2.0, 26 Nov 2015) for the full list of Secondary Objectives.
    Objetivo secundario clave:
    Comparar la eficacia de fluticasona /formoterol inhalador activado por la inspiración 125/5 microgram (2 inhalaciones 2 v/d) con Ultibro Breezhaler 85/43 microgram (1 inhalación 1 v/d) en cuanto a la concentración sérica de proteína surfactante D (SPD, surfactant protein D) en la semana 6 de cada tratamiento.

    Solamente se lista aquí el objetivo secundario clave.
    Por favor, hacer referencia al punto 7.3 del protocolo (Final Versión 2.0, 26 Nov 2015) para la lista completa de los objetivos secundarios.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female subjects aged equal or major than to 40 years at Screening visit.
    2. Adequate contraception:
    - Female subjects of child bearing potential (less than 1 year post-menopausal) must have a negative urine pregnancy test prior to first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of birth control throughout the study such as sterilisation, implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence, where this is line with the preferred and usual lifestyle of the subject or vasectomised partner.
    Note: Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for duration of study, and withdrawal are not acceptable methods of contraception).
    - Male subjects with a partner of child-bearing potential must be willing to use adequate and highly effective methods of birth control throughout the study (as defined above).
    3. Diagnosis of fixed airflow obstruction with elevated eosinophils /ACOS as evidenced by:
    - Chronic respiratory symptoms e.g. wheezing, dyspnoea, especially exertional dyspnoea) for at least 6 months prior to Screening.
    - Smoking history of equal or more than 10 or more pack years (equivalent to, for example, 20 cigarettes/day for 10 years or 10 cigarettes/day for 20 years).
    - Post-bronchodilator FEV1 / FVC ratio < 0.7 and post bronchodilator FEV1 >30 and <=60% predicted normal measured at visit 1 (GLI 2012).
    - Evidence of eosinophilic inflammation demonstrated by eosinophils in induced sputum of equal or more than 3% at Visit 1 (assessed at central laboratory) and Visit 3 (assessed at local laboratory).
    4. Subjects symptomatic at Visit 1 (CAT equal or more than 10) despite currently receiving treatment with either LAMA or LABA monotherapy or LAMA + LABA as a combination inhaler or separate inhalers.
    5. Documented history of 1 or more moderate or severe respiratory disease exacerbations (requiring treatment with systemic corticosteroids and/or antibiotics and/or hospitalisation) in the previous year.
    6. Willing and able to replace current therapy for obstructive lung disease with study medication.
    7. Able to demonstrate correct use of a BAI, Breezehaler and pMDI.
    8. Willing and able to attend all study visits and complete study assessments.
    9. Able to provide signed informed consent.
    1.Sujetos hombre o mujer de edad igual o superior a 40 años en la visita de Selección
    2.Contracepción adecuada:
    - Los sujetos de sexo femenino y en edad fértil (menos de 1 año desde la menopausia) deben obtener una prueba de embarazo en orina negativa antes de recibir la primera dosis de la medicación del estudio, no deben estar en periodo de lactancia y estar de acuerdo en usar métodos de control de la natalidad de alta eficacia a lo largo de todo el estudio, por ejemplo esterilización, implantes, inyectables, anticonceptivos orales combinados, algunos dispositivos intrauterinos, abstinencia sexual, lo que más convenga a la preferencia y el estilo de vida de la participante o tener una pareja vasectomizada.
    Nota: la abstinencia periódica (método del calendario, de la temperatura, de la posovulación), la declaración de abstinencia durante el estudio y el método de retirada no son métodos anticonceptivos aceptables.
    - Los sujetos de sexo masculino que tengan una pareja en edad fértil deben aceptar el uso de métodos de control de la natalidad adecuados y de alta eficacia a lo largo de todo el estudio (ver definición más arriba).
    3.Diagnóstico de obstrucción crónica de las vías respiratorias con eosinófilos elevados/ACOS, demostrado mediante:
    - Síntomas respiratorios crónicos (por ej. sibilancias, disnea, en especial la disnea de esfuerzo) durante al menos 6 meses antes de la Selección.
    - Antecedentes de tabaquismo de 10 o más cajetillas año (equivalente por ejemplo a 20 cigarrillos/día durante 10 años o 10 cigarrillos/día durante 20 años).
    - Cociente FEV1 / FVC después del broncodilatador < 0,7 y FEV1 >30 después del broncodilatador y <=60 % del pronosticado normal en la Visita 1 (GLI 2012).
    - Evidencia de inflamación eosinofílica demostrada por eosinófilos en esputo inducido mayor o igual a 3 % en la Visita 1 (evaluado en un laboratorio principal) y en la Visita 3 (evaluado en un laboratorio local).
    4.Sujetos sintomáticos en la Visita 1 (CAT mayor o igual a 10) a pesar de estar recibiendo tratamiento actualmente con AMAP o BAAP en monoterapia o AMAP + BAAP en un inhalador combinado o en inhaladores separados.
    5.Antecedentes documentados de una o más exacerbaciones moderadas o intensas de enfermedades respiratorias (que requirieron tratamiento con corticoides sistémicos o antibióticos u hospitalización) durante el año anterior.
    6.Con voluntad y capacidad de sustituir el tratamiento actual para le enfermedad pulmonar obstructiva por el medicamento del estudio.
    7.Capaz de demostrar un uso correcto del inhalador activado por la inspiración, Breezehaler y pMDI.
    8.Con voluntad y capacidad de asistir a todas las visitas y completar las evaluaciones del estudio.
    9.Capaz de proporcionar, firmado, el consentimiento informado.
    E.4Principal exclusion criteria
    1. Respiratory disease exacerbation between 4 weeks prior to screening and Visit 3 (Randomisation).
    2. Previous treatment with ICS.
    3. Documented evidence of alpha1-antitrypsin deficiency.
    4. Other active respiratory disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease, cystic fibrosis, bronchiolitis obliterans.
    5. Use of long-term oxygen therapy (LTOT) at least 12 hours daily or mechanical ventilation.
    6. Chest X-ray or CT scans performed prior to screening which reveal evidence of clinically significant abnormalities reflective of active disease not believed to be due to COPD.
    7. Evidence of uncontrolled cardiovascular disease.
    8. Evidence of clinically significant renal, hepatic, gastrointestinal, or psychiatric disease.
    9. Current malignancy or a previous history of cancer which has been in remission for < 5 years (basal cell or squamous cell carcinoma of the skin which has been resected is not excluded).
    10. Clinically significant sleep apnoea requiring use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.
    11. Participation in the acute phase of a pulmonary rehabilitation programme within 4 weeks prior to screening or during the study.
    12. Known or suspected history of drug or alcohol abuse in the last 2 years.
    13. Requiring treatment with any of the prohibited concomitant medications.
    14. Known or suspected hypersensitivity or contraindication to any of the study drugs or excipients.
    15. Received an investigational drug within 30 days of the Screening.
    16. Received a systemic corticosteroid within 30 days of the Screening visit.
    1.Empeoramiento de la enfermedad respiratoria entre las 4 semanas anteriores a la selección y la Visita 3 (aleatorización).
    2.Tratamiento anterior con GCI.
    3.Evidencia documentada de deficiencia de antitripsina alpha 1
    4.Otra enfermedad respiratoria activa, como por ejemplo: tuberculosis activa, cáncer de pulmón, bronquiectasia, sarcoidosis, fibrosis pulmonar, hipertensión pulmonar, enfermedad pulmonar intersticial, fibrosis quística, bronquiolitis obliterante.
    5.Uso de oxigenoterapia a largo plazo (LTOT) al menos 12 horas al día, o ventilación mecánica.
    6.Radiografía de tórax y TAC realizados antes de la selección, que revelen evidencia de anomalías clínicamente significativas que sean reflejo de una enfermedad activa cuyo origen se cree que no es la EPOC.
    7.Evidencia de enfermedad cardiovascular no controlada.
    8.Evidencia de enfermedad renal, hepática, gastrointestinal o psiquiátrica clínicamente significativas.
    9.Tumor maligno actual o antecedentes de cáncer en remisión desde hace menos de 5 años (no se excluye carcinoma de piel de células escamosas o basales que ha sido resecado).
    10.Apnea del sueño clínicamente significativa que requiera un dispositivo de presión positiva continua de las vías respiratorias (CPAP) o un dispositivo de ventilación con presión positiva no invasiva (NIPPV).
    11.Participación en la fase aguda de un programa de rehabilitación pulmonar en el plazo de 4 semanas antes de la selección o durante el estudio.
    12.Antecedentes conocidos o sospechados de drogodependencia o alcoholismo durante los últimos 2 años.
    13.Requiere tratamiento con cualquiera de los medicamentos concomitantes prohibidos.
    14.Hipersensibilidad o contraindicación conocida o sospechada a cualquiera de los fármacos del estudio o a sus excipientes.
    15.Se le administró un medicamento experimental en estudio en el plazo de 30 días de la Selección.
    16.Se le administró un corticoide sistémico en el plazo de 30 días de la selección.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in eosinophil count (percentage of total cell count) in induced sputum at Week 6
    Cambio del recuento de eosinófilos con respecto al valor inicial (porcentaje del recuento celular total) en esputo inducido en la semana 6.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluation after study end. No interim analysis planned. Please refer to section 14.21 of the protocol.
    Evaluación después de final del estudio. Sin análisis intermedio planificado. Por favor, consulte la sección 14.21 del protocolo.
    E.5.2Secondary end point(s)
    Key Secondary efficacy endpoint:
    Change from baseline in serum concentration of the SPD at Week 6

    Other secondary efficacy endpoints:

    - Change from baseline in percentage of blood eosinophils at Week 6
    - Change from baseline in serum concentration of CCL-18 at Week 6
    - Change from baseline in concentration of nitric oxide in exhaled air (bronchial FENO) at Week 3 and Week 6 (exhaled at 50 mL/s)
    - Change from baseline in alveolar nitric oxide (in a subgroup of subjects) at Week 3 and Week 6 measured at 50, 100 and 150mL/sec
    - Change from baseline in EXACT-respiratory symptoms (EXACT-RS) dyspnoea score averaged over 6-week treatment period
    - Changes from baseline in EXACT total score averaged over the 6-week treatment period
    - Changes from baseline in mean rescue medication use measured morning and evening over 6 weeks of treatment
    - Change from baseline in ACQ at Week 6
    - Change from baseline in CAT at Week 6
    - Changes from baseline in pre-dose FEV1 & FVC at Week 6
    - Changes from baseline in mean peak expiratory flow rate (PEFR) measured morning and evening (prior to taking study medication) over 6 weeks of treatment using electronic subject diary
    - Change from baseline in oscillometric parameters (R5, R20, R5 - R20, AX, RF, X5) at Week 6 of each treatment (in a subgroup)
    - Change from baseline in percentage of neutrophils, macrophages and lymphocytes in induced sputum at Week 6 of each treatment.
    Criterios secundarios clave de valoración de la eficacia:
    Cambio con respecto al valor inicial en la concentración de proteína surfactante D (SPD) en la semana 6

    Variables de eficacia secundarias:
    - Cambio con respecto al valor inicial en el porcentaje de eosinófilos en sangre en la semana 6
    - Cambio con respecto al valor inicial en la concentración sérica de CCL-18 en la semana 6
    - Cambio con respecto al valor inicial en la concentración fraccional de óxido nítrico exhalado (FeNO bronquial) en la semana 3 y en la 6 (exhalado a 50 ml/s)
    - Cambio en el óxido nítrico alveolar (en un subgrupo de sujetos) desde el inicio hasta la semana 3 y la semana 6 medido a 50, 100 y 150 ml/s.
    - Cambio con respecto al valor inicial en el promedio de la puntuación de disnea en EXACT-síntomas respiratorios (EXACT-RS) durante el periodo de 6 semanas de tratamiento
    - Cambio con respecto al valor inicial en el promedio de la puntuación total del EXACT durante el periodo de 6 semanas de tratamiento
    - Cambio con respecto al valor inicial en el uso medio de medicación de rescate medido por la mañana y por la tarde durante las 6 semanas de tratamiento
    - Cambio con respecto al valor inicial en ACQ en la semana 6
    - Cambio con respecto al valor inicial en CAT en la semana 6
    - Cambios con respecto al valor inicial en FEV1 y FVC antes de la administración del medicamento, en la semana 6
    - Cambio con respecto al valor inicial del flujo espiratorio máximo, (FEM) medido por la mañana y por la tarde (antes de tomar la medicación del estudio) durante 6 semanas de tratamiento utilizando el diario electrónico del paciente
    -Cambio con respecto al valor inicial de los parámetros oscilométricos (Rsr5, Rsr20, Rsr5 - Rsr20, AX, Fres, Xsr5) en la semana 6 de cada tratamiento (en un subgrupo)
    - Cambio con respecto al valor inicial en el porcentaje de neutrófilos, macrófagos y linfocitos en esputo inducido en la semana 6 de cada tratamiento.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Evaluation after study end. No interim analysis planned. Please refer to section 14.21 of the protocol.
    Evaluación después de final del estudio. Sin análisis intermedio planificado. Por favor, consulte la sección 14.21 del protocolo.
    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 No
    E.6.7Pharmacodynamic No
    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.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 Yes
    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 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 EEA25
    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
    Bulgaria
    Hungary
    Italy
    Poland
    Romania
    Slovakia
    Spain
    Ukraine
    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
    LVLS
    LVLS - Última visita del último sujeto reclutado
    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 months5
    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 months5
    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.1.1.1In 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: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 65
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 130
    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)
    None
    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 Decision2016-04-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-11-07
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