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    Summary
    EudraCT Number:2017-004564-35
    Sponsor's Protocol Code Number:205739
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-06-11
    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 number2017-004564-35
    A.3Full title of the trial
    A Phase IIa Randomized, Placebo-Controlled, Double-Blind (Sponsor Open) Study to Investigate the Clinical Efficacy, Safety, and Tolerability of Nemiralisib (GSK2269557) in Symptomatic COPD Participants with a History of Exacerbations
    Estudio de fase IIa aleatorizado, controlado con placebo, doble ciego (abierto para el promotor), para evaluar la eficacia clínica, seguridad y tolerabilidad de Nemiralisib (GSK2269557) en participantes con EPOC sintomática e historial de exacerbaciones
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A 12 Month Proof of Concept Phase IIa Study of Nemiralisib (GSK2269557) in Symptomatic COPD Participants with a History of Exacerbations
    Estudio de fase IIa de 12 meses con Nemiralisib (GSK2269557) en participantes con EPOC sintomática e historia de exacerbaciones.
    A.3.2Name or abbreviated title of the trial where available
    PH2a, efficacy and safety study of GSK2269557 Vs PBO in pts with COPD having history of exacerbation
    A.4.1Sponsor's protocol code number205739
    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 SponsorGlaxoSmithKline, 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 supportGlaxoSmithKline Research & Development Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointCentro de Información
    B.5.3 Address:
    B.5.3.1Street AddressC/Severo Ochoa, 2 (P.T.M.)
    B.5.3.2Town/ cityTres Cantos (Madrid)
    B.5.3.3Post code28760
    B.5.3.4CountrySpain
    B.5.4Telephone number34902202700
    B.5.5Fax number34918070479
    B.5.6E-mailes-ci@gsk.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 No
    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 nameNemiralisib
    D.3.2Product code GSK2269557
    D.3.4Pharmaceutical form Inhalation powder
    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 INNNemiralisib succinate
    D.3.9.1CAS number 1364799-98-3
    D.3.9.3Other descriptive nameGSK2269557
    D.3.9.4EV Substance CodeSUB73036
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    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.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 placeboInhalation powder
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Obstructive Pulmonary Disease (COPD)/chronic bronchitis and emphysema
    Enfermedad Pulmonar Obstructiva Crónica (EPOC)/bronquitis crónica y enfisema
    E.1.1.1Medical condition in easily understood language
    Chronic Obstructive Pulmonary Disease (COPD)/chronic bronchitis and emphysema
    Enfermedad Pulmonar Obstructiva Crónica (EPOC)/bronquitis crónica y enfisema
    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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10010953
    E.1.2Term COPD exacerbation
    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 evaluate the clinical efficacy of nemiralisib compared with placebo to reduce the annual rate of moderate and severe exacerbations in participants with COPD.
    Evaluar la eficacia clínica de nemiralisib comparado con placebo para reducir la tasa anual de exacerbaciones moderadas y graves en participantes con EPOC.
    E.2.2Secondary objectives of the trial
    -To evaluate the effect of nemiralisib compared to placebo on further efficacy parameters pertaining to exacerbations and aligned with the primary objective
    -To evaluate the effect of nemiralisib compared with placebo on respiratory symptoms and Health related quality of life (HRQoL) using Patient Reported Outcomes (PROs)
    -To evaluate the effect of nemiralisib compared to placebo on lung function
    - To evaluate the effect of nemiralisib compared to placebo on rescue medication use
    -To evaluate the population pharmacokinetics of nemiralisib
    -To evaluate the safety and tolerability of nemiralisib compared with placebo
    - Evaluar el efecto de nemiralisib en comparación con placebo sobre parámetros de eficacia adicionales en lo que respecta a exacerbaciones y alineación con el objetivo principal.
    - Evaluar el efecto de nemiralisib en comparación con placebo sobre los síntomas respiratorios y la calidad de vida relacionada con la salud (CVRS) utilizando los resultados referidos por los pacientes (RRP).
    - Evaluar el efecto de nemiralisib comparado con placebo sobre la función pulmonar.
    - Evaluar el efecto de nemiralisib comparado con placebo sobre el uso de fármacos de rescate.
    - Evaluar la farmacocinética (FC) de nemiralisib.
    - Evaluar la seguridad y la tolerabilidad de nemiralisib en comparación con placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participants are eligible to be included in the study only if all the following criteria apply:
    Age
    1. ≥40 and ≤80 years of age inclusive, at the time of signing the informed consent.
    Type of Participant and Disease Characteristics
    2. Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [GOLD, 2017] as follows: "Chronic obstructive pulmonary disease is common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflowlimitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases."
    3. Documented history of COPD exacerbation (s): ≥2 moderate exacerbations (prescription for antibiotics and/or oral corticosteroids) or ≥1 severe exacerbation (hospitalisation or visit to the emergency room) in the 12 months prior to study participation Screening (Visit 1)
    4. Smoking History: Current or former cigarette smoker with a history of cigarette smoking of ≥10 pack-years. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (Visit 1).
    Number of pack years = (number of cigarettes per day/20) x number of years smoked) (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years
    5. Symptomatic COPD: A score of ≥10 on the COPD Assessment Test (CAT) at Screening (Visit 1).
    Existing prescribed inhaled COPD maintenance therapy: Must be receiving a stable daily inhaled COPD maintenance therapy for their COPD for at least 3 months prior to Screening (Visit 1). Participants may continue their prescribed inhaled maintenance COPD therapy throughout the study (Run-in and Treatment Periods).
    Note: Participants receiving only PRN COPD medications are not eligible.
    6. Must have a post-bronchodilator (albuterol/salbutamol) FEV1/ (forced vital capacity) (FVC) ratio ≤0.70 and post-bronchodilator FEV1 ≤80% of predicted [Quanjer, 2012] documented in the last 5 years.
    7. Must not be taking antibiotics and/or oral corticosteroids for a COPD exacerbation within 6 weeks prior to Screening (Visit 1).
    8. Able to perform lung function tests reliably.9. Must have the ability to use an electronic diary on a daily basis.
    Weight
    10. Body weight ≥ 45 kg and body mass index (BMI) within the range of 16-35 kg/m2 (inclusive).
    Sex
    11. Male and female participants are eligible to participate in the study:
    a. Female participants:
    A female participant is eligible to participate if she is not pregnant (see Appendix 5 of protocol), not breastfeeding, and at least one of the following conditions applies:
    (i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of protocol OR
    (ii) A WOCBP who agrees to follow the contraceptive guidance inAppendix 5 of protocol during the 12-Month Double-Blind Treatment Period and for at least 5 half- lives (10 days) after the last dose of double-blind study treatment. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    Informed Consent
    12. Capable of giving signed informed consent as described in Appendix 3 of protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
    Los participantes son elegibles para su inclusión en el estudio solo si cumplen todos los criterios dispuestos a continuación:
    Edad:
    1. Edad ≥40 y ≤80 años, inclusive, en el momento de la firma del consentimiento informado.
    Tipo de participantes y características de la enfermedad:
    2. Diagnóstico de EPOC establecido de conformidad con la definición propuesta por la Sociedad torácica americana/Sociedad respiratoria europea [GOLD, 2017] según se indica a continuación:
    «La enfermedad pulmonar obstructiva crónica es una enfermedad frecuente, prevenible y tratable que se caracteriza por síntomas respiratorios persistentes y una limitación del flujo de aire a causa de anomalías alveolares y/o de las vías respiratorias debido a una exposición significativa a gases o partículas nocivas».
    3. Antecedentes documentados de exacerbaciones de EPOC: ≥2 exacerbaciones moderadas (prescripción de antibióticos y/o corticoesteroides orales) o ≥1 exacerbación grave (hospitalización o visita a urgencias) en los 12 meses antes de la selección para participar en el estudio (Visita 1).
    4. Antecedentes de tabaquismo: fumador actual o exfumador con antecedentes de tabaquismo de ≥10 paquetes-año. Un exfumador se define como un sujeto que ha dejado de fumar durante, al menos, 6 meses antes de la selección (Visita 1).
    Número de paquetes-año = (número de cigarrillos al día/20) x número de años fumando (p. ej., 20 cigarrillos al día durante 10 años o 10 cigarrillos al día durante 20 años, ambos casos equivalen a 10 paquetes-año).
    5. EPOC sintomática: una puntuación de ≥10 en la prueba de evaluación de la EPOC (CAT) en la selección (Visita 1).
    Tratamiento de mantenimiento inhalado prescrito para la EPOC existente: debe estar recibiendo una terapia de mantenimiento inhalada diaria para la EPOC durante un mínimo de 3 meses antes de la selección (Visita 1). Los participantes pueden continuar recibiendo su tratamiento de mantenimiento inhalado prescrito para la EPOC a lo largo del estudio (Periodos de preinclusión y de tratamiento). Nota: Los sujetos que solo reciben fármacos para la EPOC a demanda no se consideran elegibles.
    6. Debe presentar un cociente FEV1/FVC (capacidad vital forzada) posbroncodilatador (albuterol/salbutamol) ≤0,70 y FEV1 posbroncodilatador ≤80% del valor previsto [Quanjer, 2012] documentado en los últimos 5 años.
    7. No debe tomar antibióticos y/o corticoesteroides orales para la exacerbación de EPOC en los 6 meses previos a la Selección (Visita 1).
    8. Debe ser capaz de realizar las pruebas de la función pulmonar con fiabilidad.
    9. Debe ser capaz de utilizar un diario electrónico cada día.
    Peso:
    10. Peso corporal ≥45 kg e índice de masa corporal (IMC) en el intervalo de 16 a 35 kg/m2 (inclusive).
    Sexo:
    11. Los sujetos del sexo masculino y femenino son elegibles para participar en el estudio:
    a. Participantes femeninas:
    Una participante femenina es elegible para participar si no está embarazada (véase el Apéndice 5), en periodo de lactancia y se cumple, al menos, una de las siguientes condiciones:
    (i) No es una mujer en edad fértil (MEF) conforme a la definición del Apéndice 5
    O
    (ii) Una MEF que acepta seguir las guías anticonceptivas dispuestas en el Apéndice 5 durante el Periodo de tratamiento doble ciego de 12 meses y, al menos, 5 semividas (10 días) después de la última dosis del tratamiento del estudio doble ciego.
    El uso de anticonceptivos por parte de hombres y mujeres debe ser coherente con la normativa local sobre los métodos anticonceptivos para participantes en estudios clínicos.
    Consentimiento informado:
    12. Con capacidad para otorgar el consentimiento informado firmado conforme a lo descrito en el Apéndice 3, que incluye el cumplimiento con los requisitos y las restricciones dispuestas en el formulario de consentimiento (FCI) y en este protocolo.
    E.4Principal exclusion criteria
    Participants are excluded from the study if any of the following criteria apply:
    Medical Conditions
    1. Current diagnosis of asthma, according to the Global Initiative for Asthma [GINA, 2017].
    2. Less than 6 weeks elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation.
    3. Chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray (or CT scan) must be taken at Screening (Visit 1) (or historic radiograph or CT scan obtained within 3 months prior to screening). For sites in Germany: if a chest X-ray (or CT scan) within 1 year of Screening (Visit 1) is not available, approval to conduct a diagnostic chest X-ray (CT scan) will need to be obtained from the Federal Office for Radiation Protection (BfS).
    4. Diagnosis of Pneumonia (chest X-ray or CT confirmed) within the last 3 months prior to Screening (Visit 1).
    5. Other respiratory disorders: A diagnosis of α1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, active tuberculosis, lung cancer, clinically overt bronchiectasis (Note: focal bronchiectasis is not exclusionary), pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), primary pulmonary hypertension, interstitial lung diseases, or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results.
    6. Other diseases/abnormalities: A history or current evidence of clinically significant and unstabledisease such as cardiovascular (e.g., patients requiring implanted cardioverter defibrillator [ICD], pacemaker requiring a rate set>60bpm, uncontrolled hypertension, New Your Heart Association Class IV [NYHA, 1994], known left ventricular ejection fraction <30%) neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or hematological abnormalities. Significant is defined as anydisease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. (Note: Participants with adequately treated and well controlled concurrent medical conditions (e.g. hypertension or noninsulin-dependent diabetes mellitus[NIDDM]) are permitted to be entered into the study).
    7. Lung resection: Having undergone lung volume reduction surgery or lung resection for any other reason (e.g. lung carcinoma)
    8. Liver disease
    a. ALT >2xULN
    b. Total Bilirubin >1.5xULN
    i. Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%
    c. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones
    d. Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study treatment
    e. Positive hepatitis C antibody test result at Screening orwithin 3 months prior to first dose of study treatment
    f. Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
    9. Positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study treatment. NOTE: Test is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
    10. Cancer: Carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin are not excluded if the participant has been considered cured within 5 years since diagnosis.
    11. Contraindications: History of allergy or hypersensitivity to any of the studymedications (e.g. beta-agonists, PI3Kd inhibitors). In addition, participants with a history of severe milk protein allergy (e.g lactose) that, in the opinion of the investigator, contraindicates the participant’s participation are excluded.Prior/Concomitant Therapy
    12. Use of the following medications:
    - Strong inhibitors of cytochrome P450 3A4: Currently, only in vivo information is available on the in vivo metabolism of nemiralisib; and, the role of cytochrome P450s (CYPs) in the elimination of nemiralisib is based upon in vitro data. In vitro studies indicate that nemiralisib is predominantly metabolized by CYP3A4 enzymes with minor contributions from CYP1A1,CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2J2.

    Refer Protocol for other exclusions points
    Los participantes se excluirán del estudio si cumplen alguno de los siguientes criterios:
    Condiciones médicas
    1. Diagnóstico actual de asma, conforme a la Iniciativa global para el asma [GINA, 2017].
    2. Han transcurrido menos de 6 semanas desde la finalización de un ciclo de antibióticos o corticoesteroides orales para una exacerbación de EPOC reciente.
    3. Radiografía de tórax (o TC) que revela evidencias de anomalías clínicamente significativas no consideradas como debidas a la presencia de EPOC. Se debe realizar una radiografía de tórax (o TC) en la selección (Visita 1) (o TC o radiografía histórica obtenida en los 3 meses previos a la selección). Para centros en Alemania: si no es posible efectuar una radiografía de tórax (o TC) en el plazo de un año de la Selección (Visita 1), será necesario obtener la autorización para realizar una radiografía de tórax (o TC) diagnóstica de la Oficina Federal de Protección frente a la Radiación (BfS).
    4. Diagnóstico de neumonía (confirmación por radiografía de tórax o TC) en los 3 meses anteriores a la selección (Visita 1).
    5. Otros trastornos respiratorios: un diagnóstico de deficiencia de α1-antitripsina como causa subyacente de EPOC, tuberculosis activa, cáncer pulmonar, bronquiectasias (Nota: la bronquiectasia focal no es un motivo de exclusión), sarcoidosis, tuberculosis activa, cáncer pulmonar, bronquiectasia clínicamente manifiesta (Nota: la bronquiectasia focal no es motivo de exclusión), fibrosis pulmonar (Nota: las lesiones pulmonares fibróticas locales no son motivo de exclusión), hipertensión pulmonar principal, enfermedades pulmonares intersticiales o cualquier otra afección respiratoria que puede, en opinión del investigador, comprometer la seguridad del sujeto o afectar la interpretación de los resultados.
    6. Otras enfermedades/anomalías: antecedentes o evidencias actuales de enfermedad inestable y clínicamente significativa como cardiovascular (p. ej., pacientes que requieren un desfibrilador cardioversor implantable (DCI), marcapasos con una frecuencia > 60 lpm, hipertensión no controlada, de clase IV según la New York Heart Association [NYHA, 1994], fracción de eyección ventricular izquierda conocida <30%) neurológica, psiquiátrica, renal, hepática, inmunitaria, endocrina (incluyendo diabetes no controlada o enfermedad tiroidea), enfermedad de úlcera péptica o anomalías hematológicas. Significativo se define como cualquier afección que, según la opinión del investigador, pone en riesgo la seguridad del paciente a través de la participación o que afecta los análisis de eficacia o seguridad si se produce una exacerbación de la enfermedad/afección durante el estudio. (Nota: Se permite la inclusión en el estudio de sujetos con afecciones médicas concurrentes bien controladas y tratadas adecuadamente (p. ej., hipertensión o diabetes mellitus no dependiente de insulina [DMNDI]).
    7. Resección pulmonar: se ha sometido a cirugía de reducción del volumen pulmonar o resección pulmonar por cualquier motivo (p. ej., carcinoma pulmonar).
    8. Hepatopatía
    a. ALT >2 x LSN.
    b. Bilirrubina total >1,5 x LSN.
    i. Bilirrubina aislada >1,5 x LSN es aceptable si se realiza el fraccionamiento de la bilirrubina y la bilirrubina directa <35%.
    c. Antecedentes de hepatopatía crónica o actual o anomalías hepáticas o biliares conocidas (con la excepción del síndrome de Gilbert o cálculos biliares asintomáticos).
    d. Presencia del antígeno de superficie de hepatitis B (HBsAg) en la selección o en los 3 meses previos a la primera dosis del tratamiento del estudio.
    e. Resultado positivo en la prueba de anticuerpos de hepatitis C en la selección o en los 3 meses previos a la primera dosis del tratamiento del estudio.
    f. Se pueden incluir participantes con un resultado positivo para anticuerpos de hepatitis C debido a una enfermedad resuelta previa solo si se obtiene una prueba confirmatoria negativa sobre ARN de hepatitis C.
    9. Resultado positivo en la prueba de ARN de hepatitis C en la selección o en los 3 meses previos a la primera dosis del tratamiento del estudio. NOTA: La prueba es opcional y los participantes con un resultado negativo en la prueba de anticuerpos de hepatitis C no necesitan someterse a análisis del ARN de hepatitis C.
    10. Cáncer: carcinoma que no se encuentre en remisión completa desde, al menos, 5 años. El carcinoma in situ del cuello uterino, carcinoma de células escamosas y carcinoma de células basales de la piel no se excluyen si el participante se considera curado en los 5 años desde el diagnóstico.
    11. Contraindicaciones: antecedentes de alergia o hipersensibilidad a cualquiera de los fármacos del estudio (p. ej., agonistas beta, inhibidores de PI3Kd). Asimismo, se excluirán los participantes con antecedentes de alergia grave a la proteína de la leche (p. ej., lactosa) que, según la opinión del investigador, contraindique la participación del sujeto.

    Consulte el Protocolo para una lista de todos los Criterios de exclusión.
    E.5 End points
    E.5.1Primary end point(s)
    Annualised rate of on-treatment moderate and severe exacerbations as defined by Health Care Resources Utilization (HCRU)
    Tasa anual de exacerbaciones moderadas y graves durante el tratamiento conforme a la definición del Uso de Recursos Sanitarios (URS).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluated at 8 clinic visits over a 52-week treatment period
    Evaluado en 8 visitas clínicas durante un período de tratamiento de 52 semanas
    E.5.2Secondary end point(s)
    - Annualised rate of on-treatment HCRU/EXACT defined mile, moderate, and severe exacerbations
    - Time to first on treatment HCRU/EXACT defined moderate/severe exacerbation
    - Time to first on treatment HCRU/EXACT defined mild/moderate/severe exacerbation

    Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD)
    - Change from baseline in monthly weighted mean of E-RS: COPD (Total score and sub domains)
    - Proportion of responders according to ERS: COPD (Total score and sub domains)

    COPD Assessment Test (CAT)
    - Proportion of responders according to CAT at Weeks 4, 12, 28, 52
    - Change from baseline in CAT total score at Weeks 4, 12, 28, 52

    St. George’s Respiratory Questionnaire total score (measuring using SGRQ for COPD Patients (SGRQ-C))
    - Proportion of responders SGRQ-C total score at Weeks 4, 12, 28, 52
    - Change from baseline SGRQ-C total score at Weeks 4, 12, 28, 52

    Exacerbations of Chronic Pulmonary Disease Tool (EXACT)
    - Annualised rate of HCRU/EXACT events
    - Time to first HCRU/EXACT event
    - Severity and duration of each HCRU/EXACT event
    - Change from baseline in clinic visit trough pre-and post-bronchodilator Inspiratory Capacity (IC), FEV1, and FVC, at Weeks, 4, 12, 28, 52
    - Rescue Medication Use (occasions/day)
    - The percentage of rescue-free days (24- hour periods) during each month of treatment and over the 12 Month Treatment Period
    - PK concentrations and parameters
    - Incidence of Adverse Events (AEs; including serious AEs and AE of Special Interest (AESI))
    - Vital Signs (pulse rate, systolic and diastolic blood pressure) measured at each clinic visit up through Week 52 or Early Withdrawal Visit
    - 12-Lead ECG performed at Screening, Weeks 4, 12, 28, 52 or Early Withdrawal Visit
    - Clinical laboratory evaluations (haematology, clinical chemistry, urinalysis) performed at each clinic visit up through Week 52 or Early Withdrawal
    - Incidence of COPD exacerbations
    - Tasa anual de exacerbaciones leves, moderadas y graves según la definición de URS/EXACT durante el tratamiento.
    - Tiempo hasta primera exacerbación de EPOC moderada/grave según la definición de URS/EXACT durante el tratamiento.
    - Tiempo hasta primera exacerbación de EPOC leve/moderada/grave según la definición de URS/EXACT durante el tratamiento.

    Evaluación de los síntomas respiratorios (E-RS) en EPOC (E-RS: COPD)
    - Cambio frente al valor basal en la media ponderada mensual de E-RS: COPD (puntuación total y subdominios).
    - Porcentaje de respondedores según E-RS: COPD (puntuación total y subdominios).

    Cuestionario de evaluación de la EPOC (CAT)
    - Porcentaje de respondedores según CAT en las Semanas 4, 12, 28, 52.
    - Cambio frente al valor basal en la puntuación total de CAT en las semanas 4, 12, 28, 52.

    Puntuación total en el cuestionario respiratorio de St. George (determinada utilizando el SGRQ para pacientes con EPOC (SGRQ-C))
    - Porcentaje de respondedores de acuerdo con la puntuación total de SGRQ en las Semanas 4, 12, 28, 52.
    - Cambio frente al valor basal en la puntuación total de SGRQ en las Semanas 4, 12, 28, 52.

    Herramienta para las exacerbaciones de enfermedad pulmonar crónica (EXACT)
    -Tasa anual de acontecimientos según URS/EXACT.
    - Tiempo hasta el primer acontecimiento según URS/EXACT.
    - Gravedad y duración de cada acontecimiento según URS/EXACT.
    - Cambio frente al valor basal en capacidad inspiratoria (CI), FEV1 y FVC pre y posbroncodilatador determinado en la consulta médica las Semanas 4, 12, 28, 52.
    - Uso de fármacos de rescate (ocasiones/día).
    - Porcentaje de días sin fármacos de rescate (periodos de 24 horas) en cada mes de tratamiento y a lo largo de un periodo terapéutico de 12 meses.
    - Parámetros y concentraciones FC.
    - Incidencia de acontecimientos adversos (AA; incluyendo AA graves y AA de especial interés [AAEI]).
    - Constantes vitales (pulso, tensión arterial sistólica y diastólica) determinadas en cada consulta médica hasta la Semana 52 o Visita de retirada temprana.
    - ECG de 12 derivaciones realizado en la Selección, Semanas 4, 12, 28, 52 o Visita de retirada temprana.
    - Evaluaciones clínicas de laboratorio (hematología, bioquímica clínica, análisis de orina) realizadas en cada consulta médica hasta la semana 52 o visita de retirada temprana.
    - Incidencia de exacerbaciones de EPOC.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Evaluated at 8 clinic visits over a 52-week treatment period
    Evaluado en 8 visitas clínicas durante un período de tratamiento de 52 semanas
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tolerabilidad
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 No
    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 concerned11
    E.8.5The trial involves multiple Member States No
    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
    Argentina
    Germany
    Mexico
    Poland
    Spain
    Sweden
    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 months9
    E.8.9.1In the Member State concerned days24
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days24
    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: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 Yes
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 200
    F.4.2.2In the whole clinical trial 400
    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)
    Participants will not receive any additional treatment from GSK after completion of the study as other treatment options are available.
    The investigator is responsible for ensuring that consideration has been given to the poststudy care of the participant’s medical condition. At the end of the treatment period (Visit 9 or Early Withdrawal), participants should continue their COPD therapy as prescribed by their health care provider.
    Los participantes no recibirán ningún tratamiento adicional de GSK después de completar el estudio, ya que existen otras opciones de tratamiento disponibles. El investigador es responsable de asegurarse de que se proporcione a los participantes atención medica posterior tras la participación en el estudio. Al final del período de tratamiento (Visita 9 o Discontinuación prematura), los participantes deben continuar su terapia para la EPOC según lo prescrito por su médico.
    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 Decision2018-07-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-24
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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