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    Summary
    EudraCT Number:2012-003535-27
    Sponsor's Protocol Code Number:1241.36
    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:2012-09-26
    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 number2012-003535-27
    A.3Full title of the trial
    A phase III randomised, partially double-blind and placebo-controlled study of BI 207127 in combination with faldaprevir and ribavirin for chronic genotype 1 hepatitis C infection in an extended population of treatment naïve patients that includes those ineligible to receive peginterferon
    Ensayo clínico de fase III, aleatorizado, parcialmente doble ciego y controlado con placebo de BI 207127 en combinación con Faldaprevir y Ribavirina en pacientes con Hepatitis C crónica de genotipo 1 que no han recibido tratamiento previo (naïve), incluyendo a pacientes que no sean elegibles para recibir tratamiento con interferon
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial for testing efficacy and safety of BI 207127 in combination with Faldaprevir and Ribavirin in patients with Chronic Genotype 1 HCV Infection who received no previous medication, incl. patients that cannot receive peginterferon
    Ensayo clínico para estudiar la eficacia y la seguridad de BI 207127 en combinación con Faldaprevir y Ribavirina en pacientes con Hepatitis C crónica de genotipo 1 que no han recibido tratamiento previo, incluyendo pacientes que no puedan recibir tratamiento.
    A.3.2Name or abbreviated title of the trial where available
    BI207127 in combination with faldaprevir and ribavirin in treatment naive HCV GT1 infected patients
    A.4.1Sponsor's protocol code number1241.36
    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+18002430127
    B.5.5Fax number+18008217119
    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 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 nameBI 207127 NA / 200mg
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INN-
    D.3.9.1CAS number -
    D.3.9.2Current sponsor codeBI 207127 NA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 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 nameFaldaprevir / 120mg
    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 INNfaldaprevir
    D.3.9.2Current sponsor codeBI 201335 NA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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 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 Copegus
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Products 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 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 INNribavirin
    D.3.9.3Other descriptive nameRIBAVIRIN
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, soft
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    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
    E.1.1.1Medical condition in easily understood language
    chronic hepatitis C virus (HCV) infection of genotype 1
    Infección crónica por el virus de la hepatitis C (VHC) genotipo 1
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 15.0
    E.1.2Level LLT
    E.1.2Classification code 10008912
    E.1.2Term Chronic hepatitis C
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The aim of the study is to confirm efficacy and safety of treatment with 600 mg of BID BI 207127 in combination with 120 mg QD Faldaprevir (FDV) and ribavirin (RBV) for 16 or 24 weeks in ?target? chronically infected HCV genotype 1 (GT1) treatment naïve patients, including patients with compensated cirrhosis. This ?target? population excludes GT1a infected patients with the host IL28B rs12979860 CT or TT (non-CC) genotypes.

    The primary objective is to determine if there is a clinically meaningful difference between 16- and 24-week treatment durations.
    El objetivo del estudio es confirmar la eficacia y seguridad del tratamiento con 600 mg BID de BI 207127 en combinación con 120 mg QD de faldaprevir (FDV) y ribavirina (RBV) durante 16 o 24 semanas en pacientes ?diana? con infección crónica por HCV genotipo 1 (GT1) sin tratamiento previo, incluidos pacientes con cirrosis compensada. Quedan excluidos de esta población ?diana? los pacientes GT1a infectados con los genotipos IL28B rs12979860 CT o TT (no CC).

    El objetivo principal es determinar si existe alguna diferencia clínicamente significativa entre el tratamiento mantenido durante 16 y 24 semanas.
    E.2.2Secondary objectives of the trial
    The secondary objective is to determine if a minimum historical target Sustained Virologic Response (SVR) rate at 12 weeks of 71% for peginterferon (PegIFN) eligible patients and 50% for PegIFN-ineligible patients can be achieved by the combination treatments of BI 207127, FDV and RBV in target GT1 patients, including patients with compensated cirrhosis.
    El objetivo secundario es determinar si el tratamiento con BI 207127, FDV y RBV en pacientes ?diana? GT1, incluidos pacientes con cirrosis compensada, pueden conseguir un mínimo histórico de Respuesta Virológica Sostenida (SVR) del 71% en pacientes elegibles para interferón pegilado (PegIFN) y del 50% en pacientes no elegibles para PegIFN.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected HCV RNA at screening in addition to at least one of the following:
    a. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening, or
    b. liver biopsy indicating chronic HCV infection, or
    c. history of elevated alanine aminotransferase (ALT) levels at least 6 months prior to screening.
    2. HCV infection of:
    a. sub-GT1b confirmed by genotypic testing at screening; or,
    b. sub-GT1a, GT1(with undefined subtype), or mixed sub-GT1a/1b confirmed by genotypic testing at screening in patients with IL-28b CC genotype.
    3. HCV viral load ? 1,000 IU/mL at randomisation.
    4. Patients who have never been previously treated with interferon alone, interferon+RBV, PegIFN+RBV or PegIFN+RBV+an investigational/approved DAA or any other HCV treatment regimen.
    5. Results of the IL-28b genotyping (rs12979860 polymorphism) at randomisation.
    6. Availability of a liver biopsy within 3 years or fibroscan within 6 months prior to randomisation.
    7. Age 18 to 75 years (inclusive).
    8. Female patients:
    a. with documented hysterectomy,
    b. who have had both ovaries removed,
    c. with documented tubal ligation,
    d. who are post-menopausal with last menstrual period at least 12 months prior to screening, or
    e. of childbearing potential with a negative serum pregnancy test at screening and Day 1, who, if sexually active, agree to use two non-hormonal methods of birth control from the date of screening until 7 months after the last dose of RBV. Patients must agree not to breast-feed at any time from the date of screening until 7 months after the last dose of RBV. Accepted methods of contraception in the study include diaphragm with spermicidal substance, cervical caps, intrauterine devices and condoms. Note: Systemic hormonal contraceptives may not be as effective in women taking BI 207127/FDV combination therapy and are not accepted methods of contraception in the study.
    OR
    Male patients:
    a. who are documented to be sterile, or
    b. who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of RBV. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential should perform monthly pregnancy tests from the date of screening until 7 months after the last dose of RBV (tests will be provided by the sponsor).
    9. Signed informed consent form prior to trial participation
    1) Infección crónica por el virus de la hepatitis C, diagnosticada por la presencia de anticuerpos anti-HCV positivos y RNA del HCV detectado en la selección, junto con al menos uno de los siguientes criterios:
    a. anticuerpos anti-HCV positivos o RNA del HCV detectado como mínimo 6 meses antes de la selección, o
    b. biopsia hepática característica de hepatitis C crónica, o
    c. antecedentes de niveles elevados de alanina aminotransferasa (ALT) al menos 6 meses antes del periodo de selección.
    2) Infección por HCV con las siguientes características:
    a. sub-GT1b confirmada mediante pruebas de genotipado durante la selección; o,
    b. sub-GT1a, GT1(con subtipo indefinido), o subtipo 1a/1b mixto confirmada por pruebas de genotipado durante el periodo de selección en pacientes con el genotipo IL-28b CC.
    3) Carga viral del HCV ?1.000 UI/ml en el momento de la aleatorización.
    4) Pacientes que nunca hayan sido tratados previamente con interferón solo, interferón+RBV, PegIFN+RBV o PegIFN+RBV+un DAA en fase de investigación/aprobado ni otra pauta terapéutica para el HCV.
    5) Resultados del genotipado IL-28b (polimorfismo rs12979860) en el momento de la aleatorización.
    6) Disponibilidad de una biopsia hepática en los 3 últimos años o elastografìa (fibroscan) en los 6 meses previos a la aleatorización.
    7) Edad comprendida entre los 18 y 75 años (inclusive).
    8) Mujeres:
    a. con histerectomía comprobada,
    b. con extirpación de ambos ovarios,
    c. con ligadura de trompas comprobada,
    d. posmenopáusicas, con el último periodo menstrual al menos 12 meses antes de la selección o e. con posibilidad de quedar embarazadas, con prueba de embarazo en suero negativa en la selección y el día 1, que, si son sexualmente activas, acepten usar dos métodos anticonceptivos no hormonales desde la fecha de selección hasta 7 meses después de la última dosis de RBV. Las mujeres deben aceptar no amamantar a su hijo en ningún momento desde la selección y hasta 7 meses después de la última dosis de RBV. Los métodos de anticoncepción aceptados para mujeres en este estudio son el diafragma con sustancia espermicida, capuchón cervical, dispositivos intrauterinos y preservativos.
    Nota: Es posible que los anticonceptivos hormonales no sean tan eficaces en las mujeres mientras toman la combinación BI 207127/FDV y no se aceptan como métodos anticonceptivos en este estudio.
    Hombres:
    a. que se haya comprobado que son estériles o
    b. sin pareja(s) embarazada(s) y que usen de forman constante y correcta un preservativo mientras que su pareja femenina (con posibilidad de quedar embarazada) acepte usar uno de los métodos anticonceptivos médicamente aceptados desde la fecha de selección hasta 7 meses después de la última dosis de RBV. Es responsabilidad del paciente varón asegurarse de que su pareja (o parejas) no está embarazada antes de la inclusión en el estudio o de que no se quede embarazada durante la fase de tratamiento y de seguimiento.
    Las parejas femeninas con posibilidad de quedar embarazadas deben realizarse mensualmente pruebas de embarazo desde la fecha de selección hasta 7 meses después de la última dosis de RBV (el promotor proporcionará las pruebas).
    9) Formulario de consentimiento firmado antes de participar en el estudio
    E.4Principal exclusion criteria
    1. HCV infection of mixed GT (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening.
    2. HCV infection of sub-GT1a in patients with IL-28b CT or TT (non-CC polymorphisms).
    3. Liver disease due to causes other than chronic HCV infection which may include but is not limited to hemochromatosis, Wilson's disease, or autoimmune liver diseases. Note: patients with steatosis as part of the histological findings of the liver biopsy are not excluded.
    4. HIV infection.
    5. Hepatitis B virus (HBV) infection based on presence of HBs-Ag.
    6. Confirmed or suspected active malignancy or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix).
    7. History of illicit drug abuse other than cannabis or chronic alcohol abuse within 12 months prior to randomisation.
    8. Subject is not willing to comply with the precautionary measures to prevent photosensitivity (avoid excessive sun exposure and use sun block on a daily basis).
    9. A condition that is insufficiently diagnosed, treated or clinically unstable which in the opinion of investigator may put the patient at risk because of participation in this study, influence the results of this study, or limit the patient?s ability to participate in this study, including but not limited to severe chronic obstructive pulmonary disease, uncontrolled psychiatric disease.
    10. Decompensated liver disease, or history of decompensated liver disease, as evidenced by ascites, hepatic encephalopathy, history of esophageal variceal bleeding, or any other evidence of previous decompensation.
    11. Total bilirubin >2 mg/dL with ratio of direct/indirect >1.
    12. Serum albumin ?3.5 g/dL.
    13. Prothrombin time Institutional Normalised Ratio (INR) ?1.7.
    14. Clinical evidence of unstable cardiovascular disease which may further decompensate due to anemia, including unstable angina, recent myocardial infarction, cardiomyopathy, congestive heart failure, uncontrolled hypertension or significant arrhythmia.
    15. Red blood cell (RBC) disorders which include but are not limited to: thalassemia major, sickle cell anemia or G6PD deficit. Patients with traits or minor diseases (e.g. sickle cell trait or thalassemia minor) may be enrolled if the disease did not result in anemia at screening, according to the investigator?s clinical judgment.
    16. Body weight <40 kg or >125 kg.
    17. Usage of any investigational drugs within 28 days prior to randomisation, or planned usage of an investigational drug during the course of this study.
    18. Received concomitant hematopoietic growth factor within 28 days prior to enrolment.
    19. Received silymarin (milk thistle), glycyrrhizin, Sho-saiko-to (SST) or any medication listed in a restricted medication list provided in ISF within 28 days prior to randomisation, with the exception of parenteral analgesics used during liver biopsy procedure.
    20. Known hypersensitivity to any ingredient of the study drugs.
    21. Alpha fetoprotein value >100 ng/mL at screening; if >20 ng/mL and ?100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, computer tomography (CT) scan, or Medical Resonance Imaging (MRI)) within last 6 months prior to randomization.
    22. Haemoglobin <11 g/dL for women and <12 g/dL for men.
    23. Absolute neutrophil count <1,000 cells/mm3.
    24. Platelet count <70,000 cells/mm3.
    1. Infección por HCV de genotipo mixto GT (1/2, 1/3 y 1/4) diagnosticada por pruebas de genotipado en la selección.
    2. Infección por HCV de tipo sub-GT1a en selección con IL-28b CT o TT (polimorfismos no CC).
    3. Enfermedad hepática debida a causas distintas de la infección crónica por HCV entre las que se pueden incluir (sin ser una lista excluyente) hemocromatosis, enfermedad de Wilson, o enfermedades hepáticas autoinmunitarias. Nota: no quedan excluidos los pacientes con esteatosis como parte de los hallazgos histológicos de la biopsia hepática.
    4. Infección por HIV.
    5. Infección por el virus de la hepatitis B (HBV) basada en la presencia de HBs-Ag.
    6. Proceso maligno activo confirmado o sospechado o antecedentes de proceso maligno en los últimos 5 años previos al periodo de selección (con la excepción de carcinoma de células basales de la piel o carcinoma in situ de cérvix uterino, adecuadamente tratados).
    7. Antecedentes de drogadicción de drogas ilícitas distintas del cannabis o de alcoholismo crónico en los 12 meses previos a la aleatorización.
    8. El sujeto no está dispuesto a cumplir las medidas de precaución para prevenir la aparición de fotosensibilidad (evitar una excesiva exposición solar y el uso de filtros solares a diario).
    9. Cualquier proceso que no esté suficientemente diagnosticado o tratado, o se encuentre clínicamente inestable que en opinión del investigador pudiera poner al paciente en riesgo por su participación en este estudio, pudiera influir en los resultados del mismo, o pudiera limitar la capacidad del paciente para participar en el estudio, incluyendo (aunque no de forma exclusiva) enfermedad pulmonar obstructiva crónica o enfermedad psiquiátrica no controlada.
    10. Enfermedad hepática descompensada o antecedentes de enfermedad hepática descompensada, probada por ascitis, encefalopatía hepática, antecedentes de hemorragias por varices esofágicas o cualquier otra prueba de descompensación previa.
    11. Bilirrubina total >2 mg/dl con una proporción directa/indirecta >1.
    12. Albúmina sérica ?3,5 g/dl.
    13. Razón Internacional Normalizada (INR) del tiempo de protrombina ?1,7.
    14. Prueba clínica de enfermedad cardiovascular inestable que podría descompensarse aún más por anemia, como angina inestable, infarto de miocardio reciente, miocardiopatía, insuficiencia cardíaca congestiva, hipertensión no controlada o arritmias significativas.
    15. Trastornos de los eritrocitos (RBC) incluyendo (aunque no de forma exclusiva) talasemia mayor, anemia de células falciformes o déficit de G6PD. Los pacientes con rasgo de estos procesos o enfermedad menor (p. ej. rasgo talasémico o talasemia minor) pueden ser reclutados si la enfermedad no provocaba anemia durante el periodo de selección, según juicio clínico del investigador.
    16. Peso corporal <40 kg o >125 kg.
    17. Uso de cualquier fármaco en investigación durante los 28 días previos a la aleatorización, o uso planeado de cualquier fármaco en investigación durante el transcurso de este estudio.
    18. Haber recibido factor de crecimiento hematopoyético concomitante durante los 28 días previos al reclutamiento.
    19. Haber recibido silimarina (cardo mariano), glicirricina, Sho-saiko-to (SST) o cualquier otra medicación descrita en una lista de medicaciones restringidas que se proporciona en el ISF durante los 28 días previos a la aleatorización, excepto los analgésicos parenterales utilizados durante la obtención de la biopsia hepática.
    20. Hipersensibilidad conocida a cualquiera de los componentes de los fármacos del estudio.
    21. Valor de alfa-fetoproteína >100 ng/ml en la selección; si es > 20 ng/ml y ? 100 ng/ml, los pacientes pueden incluirse si no hay signos de cáncer de hígado en un estudio de representación por imágenes adecuado (p. ej. ecografía, tomografía computarizada (CT) o resonancia magnética nuclear (MRI) en los 6 meses anteriores a la aleatorización.
    22. Hemoglobina <11 g/dl para mujeres y <12 g/dl para hombres.
    23. Recuento absoluto de neutrófilos <1.000 células/mm3.
    24. Recuento de leucocitos <70.000 células/mm3.
    E.5 End points
    E.5.1Primary end point(s)
    Sustained Virologic Response at Week 12 post-treatment (SVR12): Plasma HCV RNA level <25 IU/mL at 12 weeks after EOT
    Respuesta virológica sostenida en la semana 12 tras el tratamiento (SVR12): Nivel de RNA del HCV en plasma <25 UI/ml a las 12 semanas de finalizar el tratamiento
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks after end of treatment
    12 semanas tras el fin del tratamiento
    E.5.2Secondary end point(s)
    1. SVR4: Plasma HCV RNA level <25 IU/mL at 4 weeks after EOT

    2. SVR24: Plasma HCV RNA level <25 IU/mL at 24 weeks after EOT
    1. SVR4: Nivel de RNA del HCV en plasma <25 UI/ml a las 4 semanas de finalizar el tratamiento
    2. SVR24: Nivel de RNA del HCV en plasma <25 UI/ml a las 24 semanas de finalizar el tratamiento
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. 4 weeks after end of treatment

    2. 24 weeks after end of treatment
    1. A las 4 semanas de finalizar el tratamiento
    2. A las 24 semanas de finalizar el tratamiento
    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 Yes
    E.6.11Pharmacogenomic Yes
    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 No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Brazos 1 y 2: aleatorizado,doble ciego,controlado con placebo. Brazo3(pacientes cirróticos): abierto
    Arms 1 and 2: randomised, double-blind, placebo-controlled, Arm 3 (for cirrhotic patients): open
    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 trial3
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA111
    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
    France
    Germany
    Greece
    Italy
    Korea, Republic of
    New Zealand
    Portugal
    Spain
    Taiwan
    United Kingdom
    United States
    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
    Last follow up Visit (EOO - End of Observation, at 96 weeks after End of Treatment) of the last patient undergoing the trial
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months10
    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: 550
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 590
    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 Decision2012-12-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-12-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-09-18
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