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    Summary
    EudraCT Number:2011-000484-28
    Sponsor's Protocol Code Number:LRS114688
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2011-11-18
    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 number2011-000484-28
    A.3Full title of the trial
    A randomised, double-blind, dose-finding, multicenter study of the safety, tolerability, and efficacy of GSK2251052 therapy compared to imipenem-cilastatin in the treatment of adult subjects with febrile complicated lower urinary tract infections and acute pyelonephritis.
    Estudio aleatorizado, multicéntrico, doble ciego, de búsqueda de dosis, sobre la seguridad, la tolerabilidad y la eficacia de la terapia con GSK2251052 en comparación con el uso de imipenem-cilastatina en el tratamiento de sujetos adultos con infecciones del tracto urinario inferior complicadas y febriles y con pielonefritis aguda.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of a new medicine, an intravenous antibiotic (GSK2251052) in adults, with complicated urinary tract infection of pyelonephritis.
    Estudio de un nuevo medicamento, un antibiótico intravenoso (GSK2251052), para adultos con infecciones del tracto urinario inferior complicadas con pielonefritis.
    A.3.2Name or abbreviated title of the trial where available
    A study of GSK2251052 therapy in treatment of febrile complicated lower urinary tract infections.
    A.4.1Sponsor's protocol code numberLRS114688
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGlaxoSmithKline, S.A.
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGlaxoSmithKline R&D Ltd.
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointGSK Clinical Support Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road, Stockley Park West
    B.5.3.2Town/ cityUxbridge
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number442089904466
    B.5.5Fax number442089904968
    B.5.6E-mailGSKClinicalSupportHD@gsk.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGSK2251052
    D.3.4Pharmaceutical form Lyophilisate 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 INNNone
    D.3.9.1CAS number 1093643-37-8
    D.3.9.2Current sponsor codeGSK2251052
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number750 to 1500
    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 TIENAM IV 500 mg/500 mg polvo para solución para perfusión
    D.2.1.1.2Name of the Marketing Authorisation holderMERCK SHARP AND DOHME DE ESPAÑA, S.A.
    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.3.4Pharmaceutical form Powder 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 INNIMIPENEM
    D.3.9.1CAS number 64221-86-9
    D.3.9.3Other descriptive nameIMIPENEM
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCILASTATINA SODICA
    D.3.9.1CAS number 81129-83-1
    D.3.9.3Other descriptive nameCILASTATIN SODIUM
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Infecciones complicadas del tracto urinario
    E.1.1.1Medical condition in easily understood language
    Infecciones urinarias
    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 14.0
    E.1.2Level LLT
    E.1.2Classification code 10046574
    E.1.2Term Urinary tract infection NOS
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level LLT
    E.1.2Classification code 10037606
    E.1.2Term Pyelonephritis, unspecified
    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
    Evaluar la seguridad y tolerabilidad de GSK2251052 en el tratamiento de sujetos adultos con ITUc inferior y pielonefritis (complicada y no complicada).
    Evaluar la eficacia clínica y microbiológica de GSK2251052 en sujetos adultos evaluables microbiológicamente con ITUc inferior y pielonefritis aguda (complicada y no complicada).

    To evaluate the safety and tolerability of GSK2251052 in the treatment of adult subjects with lower cUTI and pyelonephritis (complicated and uncomplicated).
    To evaluate the clinical and microbiological efficacy of GSK2251052 in microbiologically evaluable adult subjects with lower cUTI and pyelonephritis (complicated and uncomplicated).
    E.2.2Secondary objectives of the trial
    Comparar la eficacia clínica y microbiológica de GSK2251052 con imipenem-cilastatina en sujetos adultos evaluables microbiológicamente con ITUc inferior y pielonefritis aguda (complicada y no complicada).
    Evaluar la farmacocinética de GSK2251052 y caracterizar la relación farmacocinética/farmacodinámica en esta población de estudio.
    To compare the clinical and bacteriological efficacy of GSK2251052 to imipenemcilastatin in microbiologically evaluable adult subjects with lower cUTI and acute pyelonephritis (complicated and uncomplicated).
    To evaluate the pharmacokinetics of GSK2251052 and to characterise the pharmacokinetic/pharmacodynamic relationship in this study population.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    French subjects:subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
    Italian female subjects:female subject will be eligible for inclusion in this study only if they are off non-childbearing potential
    1.Adult subjects aged at least 18 years:
    N.B.Females of non-childbearing or childbearing potential may be enrolled. It is not contraindicated to enrol females of childbearing potential, however, they must have a a negative pregnancy test at study entry and must have practiced adequate contraception for at least 30
    days prior to study entry. Additionally, the subject agrees to one of the methods listed in the protocol for avoidance of pregnancy during the entire study treatment period:
    2.Subject requires hospitalisation and has clinical signs and symptoms of lower cUTI or yelonephritis(complicated or uncomplicated)as defined below, that requires parenteral treatment only with a treatment course of a minimum of 5 days and a maximum of 14 days:
    a.Lower cUTI ? subjects must have documented fever defined as >38°C oral, >38.5°C tympanic or >39°C rectal, within the last 24 hours, exceptions would be;
    i.Afebrile subjects with lower cUTI who have a white blood cell
    count(WBC)?15,000 cells/mm3
    ii.Afebrile subjects with a lower cUTI following requiring parenteral
    therapy due to a specific indication e.g.
    ?Before and during an operative procedure, when oral
    antibiotics are not indicated
    ?Or in cases where the cUTI is suspected to be due to a pathogen
    resistant to current oral antibiotics, and at least two of the following UTI
    symptoms including dysuria,
    frequency, urgency or suprapubic pain, with the presence of a
    complicating factor:
    iii.Male gender;
    iv.Current bladder instrumentation or indwelling urinary catheter that
    has to be removed two days before the end of IV study drug
    administration;
    v.Obstructive uropathy that is expected to be medically or surgically
    treated during the course of IV study drug administration;
    vi.Urogenital surgery within 7 days preceding administration of the
    first dose of study drug;
    vii.Functional or anatomical abnormality of the urogenital tract
    including anatomic malformations or neurogenic bladder (with
    voiding disturbance of at least 100 mL residual urine
    b.Acute pyelonephritis (complicated or uncomplicated): subjects must
    have documented fever defined as>38°C oral, >38.5°C tympanic
    or>39°C rectal, within the last 24 hours and flank pain or costovertebral
    angle tenderness (CVA). Complicating factors for pyelonephritis are the
    same as for complicated UTI
    3.Subject has pyuria (white blood cell[WBC] count > 10/?L(or >5/highpower
    field [HPF] in a conventional urinalysis) in unspun clean-catch
    midstream urine (MSU) or catheter urine sample or ? 10 WBC/HPF in
    spun MSU or catheter urine)
    4.Subject has Gram-negative organism(s)on direct examination of a
    Gram-stained specimen from unspun or spun MSU or catheter urine
    sample
    5.Subject has provided a pre-therapy urine specimen obtained within 48
    hours prior to the start of therapy, which when cultured has grown at
    least one and not more than two Gram-negative uropathogens at ?105
    CFU/mL
    a.A subject may be enrolled before the results of the pre-therapy urine
    culture is known, but the subject should be withdrawn from the study if
    the culture does not yield at least one but not more than two qualifying
    Gram-negative uropathogens at ?105 CFU/mL or if the culture yields
    Gram-positive uropathogens
    b.A subject with lower cUTI or pyelonephritis(complicated or
    uncomplicated)who has failed a previous antibacterial treatment
    regimen is eligible provided a urine specimen is positive for one and not
    more than two bacterial Gram-negative uropathogens at ?105
    CFU/mL.Subjects who are treatment failures due to imipenem-cilastatin
    should not be enrolled
    6.QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block
    Sujetos franceses: en Francia, un sujeto será idóneo para formar parte del estudio sólo si está afiliado o es beneficiario de una categoría de la seguridad social.
    Mujeres italianas: en Italia, una mujer será idónea para formar parte del estudio sólo si no está en edad fértil.
    1. Sujetos adultos de al menos 18 años.
    Nota: Se podrá incluir a mujeres en edad fértil y en edad no fértil. No está contraindicado incluir mujeres en edad fértil, pero estas deberán presentar una prueba de embarazo negativa al acceder al estudio y tendrán que haber utilizado métodos anticonceptivos adecuados durante al menos los 30 días anteriores a su incorporación al estudio. Además, deberán usar uno de los métodos contraceptivos que se describen en el Protocolo durante todo el tratamiento de estudio.
    2. Sujetos que necesiten ser hospitalizados y muestren signos y síntomas clínicos de ITUc inferior o pielonefritis (complicada o no complicada), tal y como se define a continuación, y que requieran tratamiento parenteral con un periodo de tratamiento de un mínimo de 5 días y un máximo de 14 días:
    a. ITUc inferior: los sujetos deberán mostrar fiebre documentada, esto es, >38°C oral, >38,5°C timpánica o >39°C rectal, durante las últimas 24 horas; las excepciones serían:
    i. sujetos afebriles con ITUc inferior que presenten un recuento leucocitario (RL) ?15.000 células/mm3 ;
    ii. sujetos afebriles con ITUc inferior además de requerir tratamiento parenteral por una indicación específica, por ejemplo:
    ? Antes y durante un procedimiento quirúrgico, cuando no estén indicados antibióticos orales
    ? O en caso cuando se sospeche que ITUc se debe a patógenos resistentes a los antibióticos orales actuales
    y al menos dos de los siguientes síntomas de ITU (disuria, frecuencia, urgencia o dolor suprapúbico), con la presencia de un factor de complicación:
    iii. sexo masculino;
    iv. instrumentación vesical actual o catéter urinario permanente retirado dos días antes de finalizar la administración del fármaco de estudio i.v.;
    v. uropatía obstructiva que se deba tratar médica o quirúrgicamente durante el transcurso de la administración i.v. del fármaco del estudio;
    vi. cirugía urogenital en los 7 días anteriores a la administración de la primera dosis del fármaco del estudio;
    vii. anormalidad funcional o anatómica del tracto urogenital, incluidas malformaciones anatómicas o vejiga neurogénica con desórdenes de micción de al menos 100 ml de orina residual.
    b. Pielonefritis aguda (complicada o no complicada): los sujetos deberán mostrar fiebre documentada, esto es, >38°C oral, >38,5°C timpánica o >39°C rectal, en las últimas 24 horas y dolor costal o sensibilidad en el ángulo costovertebral (CVA). Los factores de complicación para la pielonefritis son los mismos que para la ITU complicada.
    3. Sujetos con piuria [recuento de leucocitos [Leu] > 10/µl (o >5/campo de gran aumento (CAP) en un análisis de orina convencional) en una muestra de orina limpia no centrifugada de la parte central de la micción (MSU) o de orina obtenida por catéter o ? 10 Leu/CAP en una MSU centrifugada u orina obtenida por catéter].
    4. Sujetos que muestren microorganismos Gram-negativos en un examen directo de una muestra con tinción de Gram de orina MSU no centrifugada o centrifugada o de orina obtenida por catéter.
    5. Sujetos que presentan una muestra de orina obtenida en las 48 horas previas al inicio de la terapia, y en la que, tras el cultivo, crezca al menos uno, pero no más de dos, uropatógenos Gram-negativos con ?105 UFC/ml.
    a. El sujeto podrá incorporarse al estudio antes de saber los resultados del cultivo de orina previo a la terapia, pero deberá ser excluido si el cultivo no presenta al menos uno, y no más de dos, uropatógenos Gram-negativos clasificadores con ?105 UFC/ml, o si el cultivo muestra uropatógenos Gram-positivos.
    b. Un sujeto con ITUc inferior o pielonefritis (complicada o no complicada) para el que no haya funcionado un tratamiento antibacteriano anterior puede considerarse idóneo para el estudio, siempre que su muestra de orina sea positiva para uno, y no más de dos, uropatógenos Gram-negativos bacterianos con ?105 UFC/ml. No deberán incluirse sujetos en los que haya fracasado el tratamiento con imipenem-cilastatina.
    6. QTcB o QTcF < 450 mseg; o QTc < 480 mseg en sujetos con bloqueo de rama.
    E.4Principal exclusion criteria
    Subjects meeting any of the following criteria must not be enrolled in the
    study:
    1. Concomitant infection requiring systemic antibacterial therapy other
    than study drugs at the time of randomisation.
    2. Subject is known to have one or more of the following:
    a. A urinary catheter that is not being removed during the study (or with
    an expectation that a catheter would be inserted during therapy with
    study drug and subsequently not removed during the study period;
    (intermittent straight catheterisation is acceptable)
    b. Complete permanent obstruction of the urinary tract;
    c. A permanent indwelling catheter or comparable instrumentation
    including nephrostomy that will not be removed during IV study drug
    administration;
    d. Suspected or confirmed prostatitis;
    e. Suspected or confirmed perinephric or intrarenal abscess;
    f. A UTI suspected or confirmed to be fungal in origin (with ? 103 fungal
    CFU/mL);
    g. A UTI suspected or confirmed to be due to a Gram-positive
    uropathogen(s), with ?105 Gram-positive organism CFU/mL;
    h. A UTI known at study entry to be caused by a pathogen(s) resistant to
    the study antimicrobial agent;
    i. Known ileal loops or vesico-ureteral reflux ;
    j. Polycystic kidney disease.
    3. Subject has an APACHE II score >20.
    4. Subject has known moderate to severe impairment of renal function
    including: a calculated creatinine clearance (CrCl) of ?50 mL/min;
    requirement for peritoneal dialysis, haemodialysis, or haemofiltration;
    oliguria (less than 20 mL urine output per hour over 24 hours);
    5. Subject with an intractable lower cUTI requiring more than 14 Days IV
    treatment.
    6. Subjects with asymptomatic lower cUTI, such as subjects with spinal
    cord injury with lower cUTI or with a neurogenic bladder that are not
    able to perceive symptoms or subjects with symptoms of neurogenic
    hyper-reflexive bladder who are not able to perceive symptoms due to
    their injury.
    7. Subject with lower cUTI or pyelonephritis (complicated and
    uncomplicated) who has received any amount of a potentially
    therapeutic antibiotic within the 96 h before providing the baseline urine
    culture specimen or prior to the start of the study.
    8. Subject has Gram-positive organism(s) on direct examination of a
    Gramstained specimen of spun/unspun MSU or catheter urine.
    9. Subject is considered unlikely to survive the 4-6 week study period or
    has any rapidly progressing disease or immediately life-threatening
    illness (including acute hepatic failure, respiratory failure or septic
    shock).
    10. Subject has evidence of known or pre-existing severe hepatic
    disease (Child-Pugh score of B or C).
    11. Subject has a known baseline haemoglobin less than 10 g/dL
    ,haematocrit less than 30% and/or a known reticulocyte count of >5%
    (i.e., reticulocytes >5% of total RBC mass)
    12. Subject has known neutropenia or is anticipated to develop
    neutropenia during the course of the study (i.e., new chemotherapy
    subject), with absolute neutrophil count less than 1000 cells/mm3.
    13. Subject has a known platelet count less than 75,000 cells /mm3
    (subjects with platelet counts as low as 50,000 cells /mm3 are eligible if
    the reduction is historically stable).
    14. Subject has an immunocompromising illness; including known
    human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), organ (including bone marrow)
    transplantation, hematological malignancy, and/or immunosuppressive
    therapy, including high-dose corticosteroids (e.g., greater than 40 mg
    prednisone or equivalent per day for greater than two weeks).
    15. Subject has participated in any investigational drug or device study
    within 30 days of study entry or within 5 half-lives, whichever is longer.
    16. Subject has previously received treatment with GSK2251052.
    17. Subject has a prior history of seizures or has a CNS abnormality
    predisposing them to seizures or has a lowered seizure threshold and/or
    is using concomitant medications with seizure potential.
    18. Subject requires probenicid or valproic acid medications.
    19. Subject with a history of moderate or severe hypersensitivity to ?-
    lactam antibiotics.
    20. Subject is pregnant or nursing.
    21. Subject, in the opinion of the investigator may be significantly
    compromised by a potential drop in haemoglobin ?2.5g/dl which is not
    related to the condition under study.
    French subjects: the French subject has participated in any study using
    an investigational drug during the previous 30 days.
    Los sujetos que cumplan alguno de los siguientes criterios no deberán incluirse en el estudio:
    1. Infección concomitante que requiera una terapia antibacteriana sistémica distinta a los fármacos en estudio en el momento de la aleatorización.
    2. Sujetos que muestren uno o más de los siguientes elementos:
    a. un catéter urinario que no se vaya a retirar durante el estudio (o expectativas de tener que introducirse un catéter durante la terapia con el fármaco del estudio, que, por tanto, no se retirará durante el periodo del estudio; el sondaje directo intermitente sí es aceptable);
    b. obstrucción permanente y completa del tracto urinario;
    c. catéter permanente o instrumentación similar, incluida la nefrostomía que no se retirará durante las administración del fármaco i.v. del estudio;
    d. prostatitis posible o confirmada;
    e. abceso perinéfrico o intrarrenal posible o confirmado;
    f. ITU de origen micótico posible o confirmado (con ? 103 UFC micóticas/ml);
    g. ITU con origen posible o confirmado en un uropatógeno Gram-positivo, con ?105 UFC de microorganismos Gram-positivos/ml;
    h. ITU conocida al inicio del estudio causada por patógenos resistentes al agente antimicróbico en estudio;
    i. conductos ileales conocidos o reflujo vesicoureteral;
    j. enfermedad poliquística del riñón.
    3. Sujetos con una puntuación APACHE II > 20.
    4. Sujetos que hayan sufrido varias afecciones de la función renal, por ejemplo: un aclaramiento de creatinina (CrCl) calculado ? 50 ml/min; necesidad de diálisis peritoneal, hemodiálisis o hemofiltración; oliguria (menos de 20 ml de micción por hora durante 24 horas);
    5. Sujetos con ITUc inferior incurable que requieran más de 14 días de tratamiento i.v.
    6. Sujetos con ITUc inferior asintomática, así como sujetos con daño en la médula espinal con ITUc inferior que no pueden percibir los síntomas debido a ese daño o con vejiga neurogénica que no pueden percibir síntomas o sujetos con síntomas de vejiga neurogénica hiperreflexica que no pueden percibir síntomas debido a ese daño.
    7. Sujetos con ITUc inferior o pielonefritis (complicada y no complicada) que hayan recibido cualquier cantidad de un antibiótico posiblemente terapéutico dentro de las 96 horas previas al suministro de la muestra para el cultivo de orina basal o antes de comenzar el estudio.
    8. Sujetos que presenten microorganismos Gram-positivos en un examen directo de una muestra con tinción de Gram de orina MSU no centrifugada o centrifugada o de orina obtenida por catéter.
    9. Sujetos con pocas probabilidades de sobrevivir al periodo de 4-6 semanas del estudio o con una enfermedad de avance rápido o una enfermedad que amenace directamente su vida (como un fallo hepático agudo, un fallo respiratorio o un shock séptico).
    10. Sujetos con evidencias de una enfermedad hepática grave conocida o anterior (puntuación Child-Pugh de B o C).
    11. Sujetos con una hemoglobina basal de menos de 10 g/dl, un hematocrito inferior al 30% y/o un recuento conocido de reticulocitos de >5% (es decir, reticulocitos >5% del total de la masa de GR)
    12. Sujetos con neutropenia conocida o posibilidad de desarrollar neutropenia durante el estudio (como un sujeto nuevo de quimioterapia), con un recuento absoluto de neutrófilos inferior a 1 000 células/mm3.
    13. Sujetos con un recuento de plaquetas conocido inferior a 75 000 células/mm3 (se podrán incluir sujetos con recuentos de plaquetas de sólo 50 000 células/mm3 si esa reducción es estable en su historia).
    14. Sujetos con una enfermedad inmunosupresora, como la infección con el virus de la inmunodeficiencia humana (VIH) o el síndrome de inmunodeficiencia adquirida (SIDA), trasplante de órganos (incluida la médula espinal), neoplasia hematológica y/o terapia inmunosupresora, incluidos los corticoesteroides de dosis alta (por ejemplo, más de 40 mg de prednisona o equivalente al día durante más de dos semanas).
    15. Sujetos que hayan participado en algún estudio de dispositivo o fármaco en investigación dentro de los 30 días previos a la incorporación al estudio o en 5 vidas medias, lo que dure más.
    16. Sujetos que hayan recibido previamente tratamiento con GSK2251052.
    17. Sujetos que presenten una historia anterior de convulsiones o una anormalidad del SNC que pueda predisponerlos a convulsiones, que muestren un umbral de crisis bajo y/o que tomen fármacos concomitantes que puedan provocar convulsiones.
    18. Sujetos que necesiten tomar probenicid o ácido valproico.
    19. Sujetos con una historia de hipersensibilidad moderada o grave a antibióticos betalactámicos.
    20. Mujeres embarazadas o en periodo de lactancia.
    21. Sujetos que bajo el criterio del investigador pueden verse comprometidos significativamente por una caída potencial en la hemoglobina ? 2,5 g/dl que no se relaciona con la condición bajo estudio.
    Sujetos franceses: sujeto francés que ha participado en algún estudio que utilice un fármaco en investigación durante los 30 días previos.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoints are:
    Safety evaluation of data from clinical laboratory tests, urinalysis,
    spontaneous/elicited adverse event reporting, ECGs and vital signs in all
    subjects who had at least one dose of study medication.
    Primary efficacy outcome measure is the therapeutic response
    (combined per-subject clinical and microbiological response) at the Test
    of Cure visit in subjects who have a qualifying Gram-negative
    uropathogen at Baseline and have had a minimum of 5 days of IV
    therapy.
    Los principales criterios de valoración son:
    Evaluación de seguridad de datos obtenidos en pruebas clínicas de laboratorio, análisis de orina, informes sobre acontecimientos adversos espontáneos o provocados, ECG y constantes vitales en todos los sujetos a los que se haya administrado, al menos, una dosis del fármaco del estudio.
    La variable de valoración principal para la eficacia es la respuesta terapéutica (respuesta clínica y microbiológica combinada por sujeto) en la visita de prueba de curación en sujetos que presenten un uropatógeno Gram-negativo cualificable en el momento basal y que hayan recibido al menos 5 días de terapia i.v.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary end point is to be evaluated at the test of cure visit (5 to 9 days post IV treatment)
    En la visita de prueba de curación
    E.5.2Secondary end point(s)
    - Microbiological response at the End of IV Therapy Visit, Test of Cure
    Visit and Late Follow-Up Visit.
    - Clinical response at the End of IV Therapy Visit, Test of Cure Visit and
    Late Follow-Up Visit
    - Therapeutic response (combined clinical and microbiological
    response) at the End of IV Visit and Late Follow-Up Visit,
    ? GSK2251052 pharmacokinetics and population PK/PD in the patient
    population
    - Respuesta microbiológica en la visita al final de la terapia i.v., en la visita de prueba de curación, en la visita de revisión última,
    - Respuesta clínica
    - Respuesta terapéutica (respuesta clínica y microbiológica combinada)
    - Farmacocinética de GSK2251052 y farmacocinética/farmacodinámica de la población en la población de pacientes.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary end points are to be evaluated at the test of cure visit (5 to 9
    days post IV treatment), End of IV therapy visit and Late follow-up visit
    (21 -28 days post IV treatment)
    Los criterios secundarios de eficacia seran evaluacion en la visita de prueba de curación (5-9 días despues del tratamiento IV), Visita fin del tratamiento i.v y ? Visita de seguimiento tardío (21-28 días posteriores al tratamiento i.v.).
    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 Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    rango de dosis, doble enmascarado
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Imipenem-cilastatin
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA46
    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
    Russian Federation
    South Africa
    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
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days12
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days12
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 190
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 168
    F.4.2.2In the whole clinical trial 210
    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)
    El investigador es responsable de los cuidados del paciente después del estudio, independientemente de que GSK proporcione o no tratamiento específico post-estudio.
    No se proporcionará medicación post-estudio como parte de este protocolo.
    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 Decision2011-06-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-06-15
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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