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    Summary
    EudraCT Number:2015-003446-45
    Sponsor's Protocol Code Number:TBTCS31/A5349
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-10-15
    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 number2015-003446-45
    A.3Full title of the trial
    Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis:
    A randomized, open-label, controlled phase 3 clinical trial
    Ensayo clínico fase III, aleatorizado, abierto y controlado para evaluar el acortamiento del tratamiento de la tuberculosis pulmonar en regimenes con rifapentina
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial to shortening the treatment for pulmonary tuberculosis with rifapentin containing regimen.
    Ensayo clínico para acortar el tratamiento de la tuberculosis pulmonar con una pauta que incluye rifapentina
    A.3.2Name or abbreviated title of the trial where available
    TBTCS31
    A.4.1Sponsor's protocol code numberTBTCS31/A5349
    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 SponsorUnidad de investigación en Tuberculosis de Barcelona
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCenters for Disease COntrol and Prevention (CDC)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUnidad de investigación en Tuberculosis de Barcelona
    B.5.2Functional name of contact pointJoan A. Caylà
    B.5.3 Address:
    B.5.3.1Street AddressPlaça de Lesseps nº1
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08023
    B.5.3.4CountrySpain
    B.5.4Telephone number0034932384545353
    B.5.6E-mailjcayla@aspb.cat
    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 Priftin
    D.2.1.1.2Name of the Marketing Authorisation holderSanofi-Aventis
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameRIFAPENTINE
    D.3.4Pharmaceutical form 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 INNRIFAPENTINE
    D.3.9.1CAS number 61379-65-5
    D.3.9.4EV Substance CodeSUB10311MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 Rifadin
    D.2.1.1.2Name of the Marketing Authorisation holderSanofi-Aventis
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameRifampicin
    D.3.4Pharmaceutical form Capsule
    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 INNRIFAMPICIN
    D.3.9.1CAS number 13292-46-1
    D.3.9.4EV Substance CodeSUB10309MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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 Moxifloxacin 400mg Film-coated Tablets
    D.2.1.1.2Name of the Marketing Authorisation holderActavis
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameMoxifloxacin
    D.3.4Pharmaceutical form 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 INNMOXIFLOXACIN
    D.3.9.3Other descriptive nameMOXIFLOXACIN
    D.3.9.4EV Substance CodeSUB09086MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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: 4
    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 Myambutol
    D.2.1.1.2Name of the Marketing Authorisation holderRiemser Pharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameEthambutol
    D.3.4Pharmaceutical form 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 INNETHAMBUTOL
    D.3.9.1CAS number 74-55-5
    D.3.9.4EV Substance CodeSUB07271MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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: 5
    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 Nicotibine
    D.2.1.1.2Name of the Marketing Authorisation holderEconophar
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameIsoniazide
    D.3.4Pharmaceutical form 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 INNISONIAZID
    D.3.9.1CAS number 54-85-3
    D.3.9.4EV Substance CodeSUB08326MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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: 6
    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 Pyrafat
    D.2.1.1.2Name of the Marketing Authorisation holderRiemser Pharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 namePyrazinamide
    D.3.4Pharmaceutical form 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 INNPYRAZINAMIDE
    D.3.9.1CAS number 98-96-4
    D.3.9.4EV Substance CodeSUB10163MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary tuberculosis
    Tuberculosis pulmonar
    E.1.1.1Medical condition in easily understood language
    Pulmonary infection
    Infección pulmonar
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    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 efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis
    ? To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis
    ? Evaluar la eficacia de un régimen que contenga rifapentina para determinar si con la sustitución de únicamente rifapentina por rifampicina hace posible la reducción del tratamiento de la tuberculosis pulmonar pansensible a diecisiete semanas.
    ? Evaluar la eficacia de un régimen que contenga rifapentina y que además se sustituye el etambutol por moxifloxacino y continúa con moxifloxacino en la fase de continuación para determinar si es posible la reducción del tratamiento de la tuberculosis pulmonar pansensible a diecisiete semanas.
    E.2.2Secondary objectives of the trial
    ? To evaluate the safety of the investigational regimens
    ? To evaluate the tolerability of the investigational regimens
    ? To collect and assess biospecimens from consenting participants for the purpose of research on discovery and validation of TB biomarkers
    ? To determine the correlation of mycobacterial and clinical markers with time to culture conversion, culture status at completion of eight weeks of treatment, treatment failure, and relapse.
    ? To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs. The main objectives of the PK/PD study are to characterize study drug PK parameters and to determine relationships between treatment outcomes and PK parameters.
    ? To evaluate the pharmacokinetics of efavirenz-based antiretroviral treatment among patients with TB/HIV co-infection taking efavirenz-based combination antiretroviral therapy and TB treatment with rifapentine
    ? Evaluar la seguridad de los régimenes en investigación.
    ? Evaluar la tolerabilidad de los régimenes en investigación.
    ? Recoger y evaluar espécimenes biológicos de los participantes que acepten participar, para investigar en el descubrimiento y validación de biomarcadores de TB.
    ? Correlacionar el estado micobacterial y marcadores clínicos con el tiempo de conversión del esputo, estado del cultivo en el momento de haber recibido ocho semanas de tratamiento, fallo en el tratamiento y recaída.
    ? Para llevar a cabo estudios de farmacocinética/farmacodinámica (PK/PD) de la medicación a analizar. Los principales objetivos del estudio de PK/PD son caracterizar los parámetros de PK y determinar la relación entre estos parámetros y los resultados del tratamiento.
    ? Evaluar la farmacocinética del efavirenz como terapia antiretroviral en pacientes coinfectados por TB/VIH que estén recibiendo terapia antirretroviral con efavirenz y tratamiento de TB con rifapentina.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A. Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of ?medium? or ?high? and rifamycin resistance not detected.
    B. Age twelve (12) years or older
    C. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
    D. Women of child-bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment.
    E. Documentation of HIV infection status.
    F. For HIV-positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to study entry. HIV-positive individuals will be enrolled in a staged approach as described in Section 8.3.10.1, specifically:
    ? Group 1 (?EFV1?): receipt of efavirenz-based antiretroviral therapy (ART) for a minimum of 30 days at the time of enrollment AND a documented HIV viral load less than 200 copies/mL at or within 30 days prior to study entry, OR
    ? Group 2 (?EFV2?): for HIV-positive individuals not on ART at enrollment, planned initiation of efavirenz-based ART before or at study week 8
    G. Laboratory parameters done at or within 14 days prior to screening:
    ? Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal
    ? Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal
    ? Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal
    ? Serum or plasma potassium level greater than or equal to 3.5 meq/L
    ? Hemoglobin level of 7.0 g/dL or greater
    ? Platelet count of 100,000/mm3 or greater
    H. For all women who are not surgically sterilized or who do not meet the study definition of post-menopausal, a negative pregnancy test at or within seven (7) days prior to screening
    I. Karnofsky score greater than or equal to 60
    J. Written informed consent
    1. Sospecha de tuberculosis pulmonar y uno o más de los siguientes: a) al menos una muestra de esputo positiva para bacilos ácido-alcohol resistentes en la baciloscopia o B) al menos una muestra de esputo positiva para M. tuberculosis por Xpert MTB / RIF, con resultado semicuantitativo de la resistencia "medio" o "alto" y resistencias a rifamicinas no detectadas.
    2. Doce (12) años de edad o mayor.
    3. Una dirección de domicilio/residencia verificable dónde se le pueda visitar y el compromiso de que si cambia de domicilio informe de la nueva dirección a los miembros de estudio en el periodo que dure el estudio, fase de tratamiento y seguimiento.
    4. Las mujeres de edad fértil que no estén esterilizadas quirúrgicamente deben de aceptar usar un método anticonceptivo adecuado (método de barrera o dispositivo intrauterino no hormonal) o abstenerse de relaciones heterosexuales durante el tratamiento del fármaco del estudio.
    5. Estado documentado de la infección del VIH.
    6. Para las personas VIH-positivas, el recuento de células T CD4 tiene que ser superior o igual a 100 células / mm3 en una analítica realizada al menos en los 30 días anteriores a la inclusión en el estudio. Las personas VIH-positivas serán divididas en dos grupos según ( tal y como se describe en la sección 8.3.10.1):
    ? Grupo 1 ("EFV1"): esta recibiendo terapia antirretroviral (ART) con efavirenz al menos 30 días antes del momento de la inclusión y tiene una carga viral del VIH documentada de menos de 200 copias / ml en los 30 días previos a la inclusión del estudio, o
    ? Grupo 2 (?EFV2?): pacientes VIH positivos que no estén recibiendo terapia antirretroviral (ART) en el momento de la inclusión, y que se planea que reciban ART con efavirenz antes o en la semana 8 del estudio.
    7. Parámetros de laboratorio de analítica realizada en o dentro de los 14 días antes de la inclusión:
    ? Alanina aminotransferasa (ALT) de menos de o igual a 3 veces el límite superior de la normalidad
    ? Bilirrubina total en plasma de menos de o igual a 2,5 veces el límite superior de la normalidad
    ? Nivel de Creatinina menor que o igual a 2 veces el límite superior de la normalidad
    ? Nivel de potasio en suero o plasma mayor que o igual a 3,5 meq / L
    ? Nivel de hemoglobina de 7,0 g / dL o mayor
    ? Recuento de plaquetas de 100.000 / mm3 o superior
    8. Todas las mujeres en edad fértil que no estén esterilizadas quirúrgicamente se necesita una prueba de embarazo negativa en o dentro de los siete (7) días previos a la inclusión.
    9. Test de Karnofsky mayor o igual a 60.
    10. Firma del consentimiento informado.
    E.4Principal exclusion criteria
    A. Pregnant or breast-feeding
    B. Unable to take oral medications
    C. Previously enrolled in this study
    D. Received any investigational drug in the past 3 months
    E. More than five (5) days of treatment directed against active tuberculosis within 6 months preceding initiation of study drugs
    F. More than five (5) days of systemic treatment with any one or more of the following drugs within 30 days preceding initiation of study drugs: isoniazid, rifampin, rifabutin, rifapentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin, capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline
    G. Known history of prolonged QT syndrome
    H. Suspected or documented tuberculosis involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis
    I. Current or planned use within six months following enrollment of one or more of the following medications: HIV protease inhibitors, HIV integrase inhibitors, HIV entry and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors other than efavirenz; quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine.
    J. Weight less than 40.0 kg
    K. Known allergy or intolerance to any of the study medications
    L. Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
    M. Other medical conditions, that, in the investigator?s judgment, make study participation not in the individual?s best interest.
    N. Current or planned incarceration or other involuntary detention.
    A. Embarazo o dando lactancia materna
    B. No puede tomar medicación vía oral
    C. Previamente incluído en este estudio
    D. Ha recibido en los últimos 3 meses algún medicamento en investigación
    E. Más de cinco (5) días de tratamiento para una tuberculosis activa en los 6 meses previos a iniciar el tratamiento del estudio
    F. Más de cinco (5) días de tratamiento con alguno o más de los siguientes medicamentos en los 30 días previos a comenzar con la medicación del estudio: isoniazida, rifampicina, rifabutina, rifapentina, etambutol, pirazinamida, kanamicina, amikacina, estreptomicina, capreomicina, moxifloxacino, levofloxacino, gatifloxacino, ofloxacino, ciprofloxacino, otras fluoroquinolonas, etionamida, protionamida, cicloserina, terizidona, ácido para-aminosalicilico, linezolid, clofazimina, delamanida o bedaquilina.
    G. Síndrome de prolongación de QT conocido
    H. Sospecha o ya documentada de tuberculosis que afecte al sistema nervioso central y/o huesos y/o articulaciones, y/o tuberculosis miliar, y/o tuberculosis pericárdica.
    I. Actualmente o se planea el uso en los próximos 6 meses la toma de alguno o más de los siguientes medicamentos: inhibidores de la proteasa VIH, inhibidores de la integrasa VIH, inhibidores de entrada o de fusión de VIH, inhibidores no nucleósidos de la transcriptasa reversa que no sea efavirenz; quinidina, procainamida, amiodarona, sotalol, disopiramida, ziprasidona, o terfenadina.
    J. Peso inferior a 40.0 kg
    K. Alergia o intolerancia conocida de alguna mediación del estudio
    L. Serán excluidos del proceso de inclusión los sujetos que en el momento de la inclusión se conozca que su cepa de M. tuberculosis es resistente a alguno o más de los siguientes medicamentos: rifampicina, isoniazida, pirazinamida, etambutol, o fluoroquinolonas.
    M. Otras condiciones médicas, que, a juicio del investigador, haga que la participación en el estudio no sea apropiada para el sujeto.
    N. Actual o planeada encarcelación del sujeto u otro tipo de detención involuntaria.
    E.5 End points
    E.5.1Primary end point(s)
    ? Efficacy: TB disease-free survival at twelve months after study treatment assignment.
    ? Safety: Proportion of participants with grade 3 or higher adverse events during study drug treatment
    ? Eficacia: A los doce meses de la asignación del tratamiento del estudio, supervivencia y sin TB
    ? Seguridad: Proporción de participantes con efectos secundarios de grado 3 o superior durante el tratamiento la medicación del estudio
    E.5.1.1Timepoint(s) of evaluation of this end point
    Twelve months after study treatment
    A los doce meses de la asignación del tratamiento del estudio
    E.5.2Secondary end point(s)
    ? TB disease-free survival at eighteen months after study treatment assignment
    ? Time to stable sputum culture conversion (solid and liquid media considered separately)
    ? Speed of decline of sputum viable bacilli by automated liquid MGIT culture days to detection
    ? Proportion of participants who are culture negative at completion of eight weeks of treatment (solid and liquid media considered separately)
    ? Sensitivity analyses assuming all participants classified as ?not assessable? have a favorable outcome
    ? Discontinuation of assigned treatment for a reason other than microbiological ineligibility
    ? Estimated steady state efavirenz PK parameters including mid-dosing interval concentration
    ? A los dieciocho meses de la asignación del tratamiento del estudio, supervivencia y sin TB
    ? Establecer tiempo de conversión de esputo (tanto en medio sólido como en líquido)
    ? Velocidad en la que el esputo no presenta bacilos viables en cultivo líquido MGIT
    ? Proporción de participantes con cultivo negativo tras ocho semanas de tratamiento (tanto en medio sólido como en líquido)
    ? Análisis de sensibilidad asumiendo que todos los participantes que hayan sido clasificados como? no evaluables? tienen un resultado favorable.
    ? Discontinuación del tratamiento asignado por una razón distinta a criterios microbiológicos
    ? Se estima que los parámetros de PK de Efavirenz se mantengan estables incluído el intervalo de concentración de media dosis
    E.5.2.1Timepoint(s) of evaluation of this end point
    Eighteen months after study treatment
    A los dieciocho meses de la asignación del tratamiento del estudio
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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) Yes
    E.8.2.2Placebo No
    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 EEA7
    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
    Hong Kong
    Kenya
    Peru
    South Africa
    Spain
    Uganda
    United States
    Vietnam
    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
    La última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 100
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 100
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 2000
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 400
    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 Yes
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 2500
    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
    Ninguno
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Tuberculosis Trial Consortium
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation Aids Clinical Trial Group
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-02-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-02-09
    P. End of Trial
    P.End of Trial StatusOngoing
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