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    Summary
    EudraCT Number:2016-003020-23
    Sponsor's Protocol Code Number:1615R2132
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Restarted
    Date on which this record was first entered in the EudraCT database:2017-09-18
    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 number2016-003020-23
    A.3Full title of the trial
    A Multicenter, Randomized, Double-blind, Parallelgroup, Clinical Study of S-649266 Compared with Meropenem for the Treatment of Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, or Healthcare-associated Bacterial Pneumonia Caused by Gram-negative Pathogens
    Estudio clínico multicéntrico, aleatorizado, doble ciego, de grupos paralelos para evaluar S–649266 en comparación con meropenem para el tratamiento de la neumonía bacteriana intrahospitalaria, la neumonía bacteriana asociada a ventilación mecánica o la neumonía bacteriana asociada a la atención médica, provocadas por patógenos gramnegativos.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An international research study on human of the antibiotic S 649266 to treat Pneumonia acquired in Hospital or Health care structures or ventilator-associated, caused by Gram negative bacteria and compared to an antibiotic already on market (Meropenem)
    Estudio clínico internacional en humanos del antibiótico S 649266 para tratar la neumonía adquirida en Hospital o asociada a ventilación mecánica, causada por bacterias gramnegativas y comparado con un antibiótico ya en el Mercado (meropenem)
    A.4.1Sponsor's protocol code number1615R2132
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03032380
    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 SponsorShionogi Ltd.
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportShionogi & Co., Ltd.
    B.4.2CountryJapan
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationShionogi & Co., Ltd
    B.5.2Functional name of contact pointCorporate Communications Department
    B.5.3 Address:
    B.5.3.1Street Address3-1-8, Doshomachi 3-chome
    B.5.3.2Town/ cityChuo-ku, Osaka
    B.5.3.3Post code541-0045
    B.5.3.4CountryJapan
    B.5.4Telephone number+81662097885
    B.5.6E-mailshionogiclintrials-admin@shionogi.co.jp
    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 nameCefiderocol
    D.3.2Product code S-649266
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCefiderocol
    D.3.9.3Other descriptive nameS-649266
    D.3.9.4EV Substance CodeSUB131099
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Meropenem
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameMeropenem
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMeropenem
    D.3.9.1CAS number 96036-03-2
    D.3.9.3Other descriptive nameMeropenem trihydrate
    D.3.9.4EV Substance CodeSUB08778MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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
    Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, or Healthcare-associated Bacterial Pneumonia Caused by Gram-negative Pathogens.
    Neumonía bacteriana intrahospitalaria, la neumonía bacteriana asociada a ventilación mecánica o la neumonía bacteriana asociada a la atención médica, provocadas por patógenos gramnegativos.
    E.1.1.1Medical condition in easily understood language
    Bacterial Pneumonia Caused by Gram-negative Pathogens acquired during hospitalization or during a stay in a healthcare institution or after a patient is intubated and received mechanical ventilation.
    Neumonía bacteriana causada por patógenos gramnegativos adquirida durante hospitalización,estancia en institución de atención médica o tras intubación de un paciente que recibió ventilación mecánica
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10021881
    E.1.2Term Infections and infestations
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10076918
    E.1.2Term Hospital acquired pneumonia
    E.1.2System Organ Class 100000015664
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10065153
    E.1.2Term Ventilator associated pneumonia
    E.1.2System Organ Class 100000015664
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare all-cause mortality at Day 14 of subjects who receive S- 649266 with that of subjects who receive the comparator, meropenem, in adults with hospital-acquired bacterial pneumonia (HABP),ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP) caused by Gram-negative pathogens
    Comparar la mortalidad por cualquier causa en el día 14 de los sujetos que reciben S-649266 con la de los sujetos que reciben el medicamento de referencia, meropenem, en adultos con neumonía bacteriana intrahospitalaria (HABP), neumonía bacteriana asociada a ventilación mecánica (VABP) pneumonía bacteriana asociada a la atención médica (HCABP), provocadas por patógenos gramnegativos.
    E.2.2Secondary objectives of the trial
    Key Secondary Objectives:
    - To compare the clinical outcome of treatment with S-649266 with that of meropenem in subjects at test of cure (TOC)
     -To compare the microbiologic outcome of treatment with S-649266 with that of meropenem at TOC
    Other Secondary Objectives:
    Efficacy:
    - To compare the clinical outcome of treatment with S-649266 with that of meropenem in subjects at early assessment (EA), end of treatment (EOT), and follow-up (FU)
    - To compare the microbiologic outcome of treatment with S-649266 with that of meropenem at EA, EOT, and FU
    - To compare the all-cause mortality at Day 28 of subjects treated with S-649266 with that of subjects treated with meropenem
     -To compare the all-cause mortality during treatment and the FU period of subjects treated with S-649266 with that of meropenem
     -To compare the resource utilization required for the 2 study treatments for the study-qualifying infection
    Safety:
     -To assess the safety of S-649266
    Obj.secundarios clave:
    -Comparar el desenlace clínico del tto con S-649266 con el del tto con meropenem en sujetos en la prueba de curación (PC)
    -Comparar el desenlace microbiológico del tto con S-649266 con el del tto con meropenem en la PC
    Otros: Eficacia:
    -Comparar el desenlace clínico del tto con S-649266 con el del tto con meropenem en sujetos en la evaluación temprana(ET), en el final del tratamiento(FdT) y en el seguimiento(SEG)
    -Comparar el desenlace microbiológico del tto con S-649266 con el tto con meropenem en la ET, FdT y SEG
    -Comparar la mortalidad por cualquier causa en el día 28 de los sujetos tratados con S-649266 con la de los sujetos tratados con meropenem
    -Comparar la mortalidad por cualquier causa durante el tto y el período de seguimiento de los sujetos tratados con S-649266 con la de meropenem
    -Comparar la utilización de recursos en los 2 ttos del estudio para la infección que cualifica para el estudio
    Seguridad:
    -Evaluar seguridad de S-649266
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects 18 years or older at the time of signing informed consent
    2. Subjects who have provided written informed consent or their informed consent has been provided by Legally Authorized Representative (LAR) (Note: Country-specific rules and local Ethics Committee approval for LAR informed consent will determine whether or not and how a subject unable to comprehend or sign the informed consent is allowed to be enrolled in the study)
    3. Subjects who meet the clinical diagnosis criteria for HABP/VABP/HCABP
    4. All subjects must fulfill at least 1 of the following clinical criteria at screening:
    a. New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea (eg, respiratory rate greater than 25 breaths/minute), expectorated sputum production, or requirement for mechanical ventilation
    b. Hypoxemia (eg, a partial pressure of oxygen [PaO2] less than 60 mm Hg while the subject is breathing room air, as determined by arterial blood gas [ABG], or worsening of the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2])
    c. Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in the amount of positive end-expiratory pressure
    d. New onset of or increase in (quantity or characteristics) suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination
    5. All subjects must have at least 1 of the following signs:
    a. Documented fever (ie, core body temperature [tympanic, rectal, esophageal] not less than [NLT] 38°C [100.4°F], oral temperature NLT
    37.5°C, or axillary temperature NLT 37°C)
    b. Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] not more than [NMT] 35°C [95.0°F], oral temperature NMT 35.5°C and axillary temperature NMT 36°C)
    c. Leukocytosis with a total peripheral white blood cell (WBC) count NLT 10,000 cells/mm3
    d. Leukopenia with total peripheral WBC count NMT 4500 cells/mm3
    e. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear
    6. All subjects must have a chest radiograph during screening or have a previous chest radiograph within 48 hours prior to randomization showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia. A computed tomography (CT) scan in the same time window showing the same findings could also be acceptable.
    7. All subjects must have evidence of a Gram-negative infection involving the lower respiratory tract as documented by 1 or more of the following:
    a. Gram stain of lower respiratory secretions showing Gram-negative bacteria either alone or mixed with Gram-positive bacteria at or within 72 hours prior to randomization
    b. Microbiologic culture of respiratory tract secretions within 72 hours prior to randomization identifying Gram-negative aerobic bacteria
    c. Other diagnostic tests, including molecular tests, which provide evidence of Gram-negative bacterial infection of the lower respiratory tract
    d. Pneumonia highly suspected to be due to a Gram-negative bacteria based on prior antibiotic use or local epidemiologic evidence of Gramnegative
    infection outbreak.
    8. Subject is male (no contraception required) or female (if woman of child-bearing potential, must use highly effective birth control method, see protocol for details in line with CTFG recommendations)
    9. Subjects who failed empiric therapy will be allowed in this study. However, confirmation of both clinical and microbiological failure is necessary: see protocol for details
    1.Sujetos mayores de 18 años en el momento de firmar el consentimiento informado
    2.Sujetos que hayan proporcionado su consentimiento informado por escrito o cuyo consentimiento informado haya sido proporcionado por un representante legalmente autorizado (nota: las normas específicas de cada país y la aprobación del comité de ética local del consentimiento informado del representante legalmente autorizado determinarán si un sujeto incapaz de comprender o firmar el consentimiento informado puede o no ser inscrito en el estudio)
    3.Los sujetos que cumplan con los criterios de diagnóstico clínico de HABP/VABP/HCABP
    4.Todos los sujetos deben cumplir al menos 1 de los siguientes criterios clínicos en la selección:
    a.Nueva aparición o empeoramiento de los síntomas o signos pulmonares, como tos, disnea, taquipnea (esto es, frecuencia respiratoria > 25 respiraciones/minuto), expectoración con esputo o necesidad de ventilación mecánica
    b.Hipoxemia (esto es, una presión parcial de oxígeno [PaO2] < 60 mm Hg mientras el sujeto respira el aire ambiente, determinada por gasometría arterial [GA], o empeoramiento de la relación de la PaO2 con la fracción de oxígeno inspirado [PaO2/FiO2])
    c.Necesidad de cambios agudos en el sistema de soporte ventilatorio para mejorar la oxigenación, determinada por el empeoramiento de la oxigenación (GA o PaO2/FiO2) o necesidad de cambios en la cantidad de presión positiva al final de la espiración
    d.Nueva aparición o aumento (en cantidad o características) de las secreciones respiratorias succionadas, que muestren evidencia de inflamación y ausencia de contaminación
    5.Todos los sujetos deben presentar al menos uno 1 de los siguientes signos:
    a.Fiebre documentada (esto es, temperatura corporal central [timpánica, rectal, esofágica] ≥ 38 °C [100,4 °F], temperatura oral ≥ 37,5 °C, o temperatura axilar ≥ 37 °C)
    b.Hipotermia (esto es, temperatura corporal central [timpánica, rectal, esofágica] ≤ 35 °C [95,0 ° F], temperatura oral ≤ 35,5 °C y temperatura axial ≤ 36 °C)
    c.Leucocitosis con un recuento total de glóbulos blancos (GB) periféricos ≥ 10 000 células/mm3
    d.Leucopenia con recuento total de glóbulos blancos periféricos ≤ 4500 células/mm3
    e.Más de un 15% de neutrófilos inmaduros (en banda) observados en frotis de sangre periférica
    6.A todos los sujetos se les debe realizar una radiografía de tórax durante la selección o una radiografía de tórax realizada en las 48 horas anteriores a la asignación al azar que demuestre la presencia de infiltrado nuevo o progresivo que haga sospechar de neumonía bacteriana. También se puede aceptar una tomografía axial computarizada (TAC) en el mismo período de tiempo que muestre los mismos hallazgos
    7.Todos los sujetos deben tener sospecha de una infección gramnegativa que afecte a las vías respiratorias inferioressegún1 o más de lo siguiente:
    a.Tinción gram de las secreciones de las vías respiratorias inferiores que muestren bacterias gramnegativas, solas o mezcladas con bacterias grampositivas en la aleatorización o en las 72 horas anteriores a la misma
    b.Cultivo microbiológico de la secreciones de las vías respiratorias realizado en las 72 horas anteriores a la aleatorización en el que se identifiquen bacterias aeróbicas gramnegativas
    c.Otras pruebas diagnósticas, incluidas pruebas moleculares, que proporcionen evidencia de infección bacteriana gramnegativa en las vías respiratorias inferiores
    d.Neumonía que se sospeche que es debida principalmente a bacterias gramnegativas con base en el uso anterior de antibióticos o evidencia epidemiológica local de brote de infección gramnegativa
    8.El sujeto es varón (no se necesita método anticonceptivo), o mujer (si es fértil, debe usar métodos anticonceptivos altamente eficaces, ver detalles en protocolo en línea con recomendaciones CTFG)
    9.Los sujetos en quienes haya fracasado el tratamiento empírico podrán participar en este estudio. Sin embargo, se necesitará confirmar el fracaso clínico y microbiológico si fuera necesario: ver protocolo para más detalles.
    E.4Principal exclusion criteria
    1. Subjects who have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of gastric contents, inhalation injury)
    2. Subjects who have a history of any hypersensitivity to cephalosporins or to carbapenems, or severe hypersensitivity to any other type of β-lactams other than cephalosporins and carbapenems (eg, penicillins,monobactams), or hypersensitivity to linezolid (Note: For β lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)
    3. Subjects with a Gram-negative infection caused by a carbapenemresistant pathogen, if known at the time of randomization (Note: Subjects who have a carbapenem-resistant pathogen identified after randomization should be evaluated clinically before discontinuation of study treatment.)
    4. Subjects with coinfection caused by invasive aspergillosis, mucormycosis or other highly lethal mold
    5. Subjects who have central nervous system infection (eg, meningitis, brain abscess, shunt infection)
    6. Subjects with cystic fibrosis
    7. Subjects in refractory septic shock, defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at the time of randomization
    8. Subjects with neutropenia (ie, polymorphonuclear neutrophils <500 cells/μL)
    9. Female subjects who have a positive pregnancy test at screening, who are lactating, or who refuse to use 1 of the previously specified methods of contraception
    10. Subjects with an Acute Physiology and Chronic Health Evaluation II (APACHE) II score of > 35
    11. Subjects who have received potentially effective antibiotic therapy for a continuous duration of more than 24 hours during the previous 72 hours prior to randomization (Note: Subjects failing empiric therapy as defined in inclusion criterion 9 may be eligible for inclusion.)
    12. Subjects with any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data
    13. Subjects receiving peritoneal dialysis (hemofiltration and hemodialysis are permitted)
    14. Subjects requiring continued treatment with methotrexate, procainamide, probenecid, monoamine oxidase inhibitors, or valproic acid (see Section 5.2)
    15. Subjects who have received another investigational drug or device within 30 days prior to study entry
    16. Subjects who have previously been randomized in this study or have previously received S-649266
    17. Subjects with 1 or more of the following laboratory abnormalities in baseline specimens: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin level > 3
    times the upper limit of normal (ULN), absolute neutrophil count <
    100/μL, platelet count < 40,000/μL
    18. Subjects with bronchiectasis with symptoms of persistent or
    recurrent bronchial infection related to irreversibly damaged and dilated
    bronchi; namely, subjects with clinical bronchiectasis
    19. Subjects with lung abscesses
    1. Los sujetos con neumonía bacteriana conocida o presunta adquirida en la comunidad, neumonía atípica, neumonía vírica o neumonía química (incluyendo aspiración de contenido gástrico y lesión por inhalación)
    2. Sujetos con antecedentes de hipersensibilidad a las cefalosporinas o a los carbapenems, o hipersensibilidad grave a cualquier otro tipo de betalactámicos que no sean las cefalosporinas o los carbapenems (por ej., penicilinas, monobactámicos), o hipersensibilidad al linezolid (nota: para los betalactámicos, los antecedentes de erupción leve seguida de una nueva exposición sin acontecimientos no son contraindicación para la participación)
    3. Sujetos con una infección gramnegativa provocada por un patógeno resistente al carbapenem, si se conoce en el momento de la aleatorización (nota: los sujetos en los que se haya encontrado un patógeno resistente al carbapenem después de la aleatorización deben evaluarse clínicamente antes de la interrupción del tratamiento del estudio).
    4. Sujetos con coinfección provocada por aspergilosis invasiva, mucormicosis u otro hongo sumamente letal
    5. Sujetos con infección en el sistema nervioso central (por ej., meningitis, absceso cerebral, infección de la derivación)
    6. Sujetos con fibrosis quística.
    7. Sujetos en shock séptico refractario, definido como una hipotensión persistente a pesar de una reanimación adecuada con líquidos o a pesar de un tratamiento vasopresor en el momento de la aleatorización
    8. Sujetos con neutropenia (es decir, neutrófilos polimorfonucleares < 500 células/μl)
    9. Mujeres con un resultado positivo en la prueba de embarazo en la selección, que estén en periodo de lactancia o que se nieguen a usar 1 de los métodos anticonceptivos indicados anteriormente
    10. Sujetos con una puntuación > 35 en el índice de evaluación de la enfermedad crónica y la fisiología aguda (APACHE) II
    11. Sujetos que hayan recibido tratamiento antibiótico potencialmente efectivo durante más de 24 horas continuadas en las 72 horas anteriores a la aleatorización (nota: los sujetos en los que fracase el tratamiento empírico como se define en el criterio de inclusión 9 pueden ser elegibles para participar.)
    12. Sujetos con cualquier afección o circunstancia que, según la opinión del investigador, comprometan la seguridad del sujeto o la calidad de los datos del estudio
    13. Los sujetos que estén recibiendo diálisis peritoneal (hemofiltración y hemodiálisis) pueden participar
    14. Sujetos que requieran tratamiento continuado con metotrexato, procainamida, probenecid, inhibidores de la monoaminooxidasa o ácido valproico (véase la sección 5.2)
    15. Sujetos que han recibido o usado otro fármaco o dispositivo en investigación en los 30 días anteriores a su inclusión en el estudio
    16. Sujetos aleatorizados con anterioridad en este estudio o que han recibido anteriormente S-649266
    17. Sujetos con 1 o más anomalías de laboratorio siguientes en las muestras basales: aspartato aminotransferasa (ASAT), alanina aminotransferasa (ALAT), fosfatasa alcalina, o nivel de bilirrubina total > 3 veces el límite superior de la normalidad (LSN), recuento absoluto de neutrófilos < 100/μl, recuento de plaquetas < 40 000/μl
    18. Sujetos con bronquiectasia con síntomas de infección bronquial persistente o recurrente relacionada con bronquios dilatados o dañados irreversiblemente; en concreto, sujetos con bronquiectasia clínica
    19. Sujetos con abscesos pulmonares
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoint:
    All-cause mortality at Day 14 for S-649266 or the active-comparator, meropenem.
    Variable principal:
    Cualquier causa de mortalidad en el día 14 de S-649266 o del comparador activo, meropenem
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 14
    Día 14
    E.5.2Secondary end point(s)
    Key secondary endpoints:
    - The clinical outcome of treatment with S-649266 or meropenem per subject at TOC
    Key secondary endpoints:
    - The clinical outcome of treatment with S-649266 or meropenem per subject at TOC
    - The microbiologic outcome of treatment with S-649266 or meropenem per subject at TOC
    Other secondary efficacy:
    - The clinical outcome of treatment with S-649266 or meropenem per subject at EA, EOT, and FU
    - The microbiologic outcome of treatment with S-649266 or meropenem per subject at EA, EOT, and FU
    - The all-cause mortality at Day 28
    - The all-cause mortality during the full duration of the study
    - The resource utilization required for the treatment of the study qualifying infection
    Objetivos secundarios clave:
    -Comparar el desenlace clínico del tratamiento con S-649266 con el del tratamiento con meropenem en sujetos en la prueba de curación (PC)
    -Comparar el desenlace microbiológico del tratamiento con S-649266 con el del tratamiento con meropenem en la PC
    Otros objetivos secundarios: Eficacia:
    -Comparar el desenlace clínico del tratamiento con S-649266 con el del tratamiento con meropenem en sujetos en la evaluación temprana (ET), en el final del tratamiento (FdT) y en el seguimiento (SEG)
    -Comparar el desenlace microbiológico del tratamiento con S-649266 con el tratamiento con meropenem en la ET, FdT y SEG
    -Comparar la mortalidad por cualquier causa en el día 28
    -Comparar la mortalidad por cualquier causa durante el studio
    -Comparar la utilización de recursos en los 2 tratamientos del estudio para la infección que cualifica para el estudio
    E.5.2.1Timepoint(s) of evaluation of this end point
    Clinical and Microbiological outcome will be evaluated at TOC, EA, EOT, and FU.
    The all-cause mortality will be also evaluated at Day 28 and until end of study.
    Facility utilization will be assessed by determination of the time in 24- hour days associated with the treatment of the infection.
    Se evaluará el desenlace clínico y microbiológico en PC,ET, FdT y SEG.
    Se evaluará también la mortalidad por cualquier causa en el día 28 y hasta final de studio.
    La utilización de la instalación se evaluará mediante la determinación del tiempo en días de 24 horas asociado con el tratamiento de la infección.
    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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA39
    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
    Belgium
    Brazil
    Canada
    Colombia
    Czech Republic
    Estonia
    France
    Georgia
    Germany
    Hungary
    Israel
    Japan
    Latvia
    Philippines
    Russian Federation
    Serbia
    Spain
    Taiwan
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of study treatment + 28 days.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    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: 150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 150
    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 Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Subjects may not be able to understand or personally sign the ICF at the time of screening due to their medical conditions. In this case the consent process will follow local Country requirement.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 94
    F.4.2.2In the whole clinical trial 300
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    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 Decision2017-09-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-09-15
    P. End of Trial
    P.End of Trial StatusRestarted
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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