Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37736   clinical trials with a EudraCT protocol, of which   6184   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-002682-19
    Sponsor's Protocol Code Number:PHI113633
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-10-01
    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 number2013-002682-19
    A.3Full title of the trial
    A Phase 2B, randomized, blinded, dose-ranging, active-controlled, parallel-group, multi-center study to evaluate the dose response relationship of GSK1278863 over the first 4 weeks of treatment and evaluate the safety and efficacy of GSK1278863 over 24 weeks in hemodialysis-dependent subjects with anemia associated with chronic kidney disease who switch from recombinant human erythropoietin.
    Estudio multicéntrico aleatorizado de fase 2B, de rango de dosis, ciego, de grupos paralelos, controlado con fármaco activo, para evaluar la relación dosis-respuesta de GSK1278863 durante las 4 primeras semanas de tratamiento, y evaluar la seguridad y eficacia de GSK1278863 durante 24 semanas, en pacientes con anemia asociada a enfermedad renal crónica que requieren hemodiálisis y que hasta ahora recibían eritropoyetina humana recombinante.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of a new drug's effect on anemia in subjects with impaired kidney function who are undergoing hemodialysis
    Estudio de como la medicación puede tratar la anemia en pacientes con insuficiencia renal crónica que requieran diálisis.
    A.4.1Sponsor's protocol code numberPHI113633
    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
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd
    B.5.2Functional name of contact pointClinical Trials Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road, Stockley Park west
    B.5.3.2Town/ cityUxbridge, Middlesex
    B.5.3.3Post codeUB11 - 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 0208 990 44 66
    B.5.5Fax number+44 0208 990 12 34
    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.3.2Product code GSK1278863
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNone
    D.3.9.1CAS number None
    D.3.9.3Other descriptive nameGSK1278863
    D.3.9.4EV Substance CodeSUB72830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code GSK1278863
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNone
    D.3.9.1CAS number None
    D.3.9.3Other descriptive nameGSK1278863
    D.3.9.4EV Substance CodeSUB72830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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.3.2Product code GSK1278863
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNone
    D.3.9.1CAS number None
    D.3.9.3Other descriptive nameGSK1278863
    D.3.9.4EV Substance CodeSUB72830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 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.3.2Product code GSK1278863
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNone
    D.3.9.1CAS number None
    D.3.9.3Other descriptive nameGSK1278863
    D.3.9.4EV Substance CodeSUB72830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameepoetina
    D.3.4Pharmaceutical form
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNepoetina
    D.3.9.1CAS number 11096-26-7
    D.3.9.4EV Substance CodeSUB13707MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU/kg international unit(s)/kilogram
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number720
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARBEPOETIN ALFA
    D.3.9.1CAS number 209810-58-2
    D.3.9.4EV Substance CodeSUB12486MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg/kg microgram(s)/kilogram
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number0
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Anemia associated with chronic kidney disease.
    Anemia asociada a enfermedad renal crónica.
    E.1.1.1Medical condition in easily understood language
    Anemia associated with chronic kidney disease
    Anemia asociada a enfermedad renal crónica.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10064848
    E.1.2Term Chronic kidney disease
    E.1.2System Organ Class 100000004857
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Characterize the dose-response relationship between GSK1278863 and Hgb at Week 4.
    Caracterizar la relación dosis-respuesta entre GSK1278863 y la Hb en la semana 4.
    E.2.2Secondary objectives of the trial
    -Characterize the ability of GSK1278863 to
    achieve Hgb within the target range (10.0 to
    11.5 g/dL).
    -Characterize the effect of GSK1278863 on
    measures of iron metabolism and utilization, on indices of hematopoiesis, EPO and on Vascular Endothelial Growth Factor (VEGF)
    -Characterize the steady-state population
    pharmacokinetic (PK) of GSK1278863 and
    metabolites.
    -Assess the safety and tolerability of GSK1278863 following once daily (QD) administration for 24 weeks.
    - Caracterizar la capacidad de GSK1278863 para lograr un valor Hb en el intervalo deseado (10,0 a 11,5 g/dl).
    - Caracterizar el efecto de GSK1278863 sobre las medidas del metabolismo y la utilización del hierro, los índices de hematopoyesis, la EPO y el factor de crecimiento del endotelio vascular (VEGF).
    - Caracterizar la farmacocinética (FC) poblacional en equilibrio estacionario de GSK1278863 y sus metabolitos.
    - Evaluar la seguridad y tolerabilidad de GSK1278863 tras su administración una vez al día (1 v/d) durante 24 semanas.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects are eligible if they meet all of the inclusion criteria below. Generalcriteria (Week -4 verification only)
    1.Age: >18 years of age.
    2.Gender: Female and male subjects.
    ? Females: If of childbearing potential, must agree to use one of the approved contraception methods as outlined in Section 11.5 from Screening until completion of the Follow-up Visit OR Of non-childbearing potential defined a pre-menopausal females with a documented tubal ligation, hysterectomy , or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 IU/L and estradiol <or= 10 pmol/L is confirmatory]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved contraception methods if they wish to continue their HRT during the stud Otherwise they must discontinue HRT to allow confirmation of post-menopaus status prior to study enrolment. For most forms of HRT, at least 2 weeks must elapse between the cessation of therapy and the blood draw; this interval depen on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
    ? Males: must agree to use one of the approved contraceptive methods as outline in Section 11.5 from the time of Screening until completion of the Follow-up Visit.
    3. QTc: QTcB <470 msec or QTcB <480 msec in subjects with bundle branch block.
    There is no QTc inclusion criterion for a subject with a predominantly paced rhyth CKD-relatedcriteria
    4. Dialysis frequency: On hemodialysis (HD) three to five times weekly for at least weeks prior to Week -4 Screening through Week 4.
    NOTE: Combination methods including hemofiltration (HF) or ultrafiltration (UF with HD are allowed. However, the type of dialysis (HD, hemodiafiltration (HDF) UF) should not change during the study.
    5. Dialysis adequacy: A single-pool Kt/Vurea of >or=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%.
    NOTE: Only needs confirming at Week -4.
    6. Hemoglobin: Baseline Hgb of 9.0-11.5 g/dL as outlined in Section 4.2 (may rescreen in a minimum of 2 weeks).
    7. Stable rhEPO dose: Using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses varying by no more than 50% during the 4 weeks prior to Week -4. At Day 1 (randomization), confirm that total weekly dose varied by no more than 50% during the screening period.
    8. Iron replacement therapy: Subjects may be on stable maintenance oral or IV (<or= 100mg/week) iron supplementation. If subjects are on oral or IV iron, then doses mus stable for the 4 weeks prior to Week -4, during the screening phase, and through the first 4 weeks after Randomization.
    Podrán participar los sujetos que cumplan todos los criterios de inclusión siguientes.
    Criterios generales (solo en la verificación de la semana 4)
    1. Edad: >18 años.
    2. Sexo: varones y mujeres.
    - Mujeres: si son capaces de procrear, deben acceder a utilizar uno de los métodos anticonceptivos aprobados que se describen en la sección 11.5 desde la selección hasta el final de la visita de seguimiento; O no tener capacidad de procrear, lo que se define como una mujer premenopáusica con una ligadura de trompas, una histerectomía o una ovariectomía documentadas; O ser postmenopáusica, lo que se define como 12 meses de amenorrea espontánea [los casos dudosos se confirmarán con una muestra de sangre con valores simultáneos de folitropina (FSH) de 23,0-116,3 UI/l y estradiol de <10 pmol/l]. A las mujeres que estén recibiendo tratamiento hormonal sustitutivo (THS) y cuya situación menopáusica esté en duda se les exigirá utilizar los métodos anticonceptivos indicados en caso de desear continuar con el THS durante el estudio. De lo contrario, deberán interrumpir el THS para poder confirmar la situación postmenopáusica antes de su inclusión en el estudio. Para la mayoría de las formas de THS, deberán transcurrir al menos 2 semanas entre el cese del tratamiento y la extracción de sangre; este intervalo dependerá del tipo y la posología del THS. Tras la confirmación de la situación postmenopáusica, podrán reanudar el THS durante el estudio sin utilizar un método anticonceptivo.
    - Varones: deberán comprometerse a utilizar uno de los métodos anticonceptivos aprobados que se describen en la sección 11.5 desde el momento de la selección hasta la finalización de la visita de seguimiento.
    3. QTc: QTcB < 470 ms o QTcB < 480 ms en los pacientes con bloqueo de rama. No se aplicará ningún criterio de inclusión basado en el QTc si el sujeto tiene un ritmo de marcapasos predominante.
    Criterios relacionados con la NC
    4. Frecuencia de la diálisis: En hemodiálisis (HD) de tres a cinco veces por semana durante al menos 4 semanas desde antes de la selección en la semana 4 hasta la semana 4.
    NOTA: Se permiten los métodos combinados de hemofiltración (HF) o ultrafiltración (UF) con la HD. Sin embargo, el tipo de diálisis (HD, hemodiafiltración (HDF) o UF) no debe cambiar durante el estudio.
    5. Idoneidad de la diálisis: un Kt/Vurea monocompartimental de ?1,2, basado en un valor histórico obtenido durante el mes anterior para garantizar que la diálisis es suficiente. Si el Kt/Vurea se desconoce, se usará una media de los 2 últimos valores de la tasa de reducción de la urea (TRU) de al menos el 65%.
    NOTA: Solo es necesaria la confirmación en la semana 4.
    6. Hemoglobina: Hb basal de 9,0-11,5 g/dl, como se indica en la sección 4.2 (se puede repetir la selección al cabo de un mínimo de 2 semanas).
    7. Dosis estable de rhEPO: uso de la misma rhEPO (epoetinas o sus biosimilares, o darbepoetina), con dosis totales semanales que no varíen en más de un 50% durante las 4 semanas previas a la semana 4. El día 1 (aleatorización), se confirmará que las dosis totales semanales no variaron en más de un 50% durante el periodo de selección.
    8. Tratamiento de reposición de hierro: Los sujetos pueden recibir suplementos de hierro en dosis de mantenimiento estables por vía oral o IV (<100 mg/semana). Si los sujetos reciben hierro por vía oral o IV, las dosis deberán permanecer estables durante las 4 semanas previas a la semana 4, la fase de selección y las 4 primeras semanas posteriores a la aleatorización.
    E.4Principal exclusion criteria
    Subjects are not eligible if they meet any criteria below.
    CKD-relatedcriteria
    1.Dialysis modality:Planned change from HD to peritoneal dialysis within the study time period.
    2.Renal transplant:Pre-emptive or scheduled renal transplant.
    3.High rhEPO dose:An epoetin dose of >or=360 IU/kg/week IV or darbepoetin dose of >or=1.8 µg/kg/week IV within the prior 8 weeks through Day 1 (randomization).
    4.Mircera:Use of Mircera (methoxy polyethylene glycol epoetin beta) within the prior 8 weeks through Day 1 (randomization).
    Laboratorytest-based criteria (Week -4 verification only)
    5.Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
    6.Folate: <2.0 ng/mL (<4.5 nmol/L) (may rescreen in a minimum of 4 weeks).
    7.Ferritin:<100 ng/mL (<100 ug/L).
    8.Transferrin saturation (TSAT):Outside of the reference range. Cardiovasculardisease-related criteria
    9.Myocardial infarction or acute coronary syndrome:Within the 8 weeks prior to Screening through Day 1 (randomization).
    10.Stroke or transient ischemic attack:Within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
    11.Heart failure:
    ?Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Week -4 Screening through Day 1 (randomization).
    ?Symptomatic right heart failure diagnosed prior to Week -4 Screening through Day 1 (randomization).
    12.Hypertension:Defined using pre-dialysis vitals (Week -4, Day 1) of DBP >100 mmHg or SBP >170 mmHg.
    13.Thrombotic disease:History of thrombotic disease, except vascular access thrombosis, within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
    Other disease-relatedcriteria
    14.Ophthalmology disease:Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam as outlined in Section 11.6.
    15.Inflammatory disease:Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Week -4 Screening through Day 1 (randomization).
    16.Hematological disease:Any hematological disease including those affecting platelets, white or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1 (randomization).
    17.Liver disease:Current liver disease, known hepatic or biliary abnormalities or evidence at Screening of abnormal liver function tests or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
    18.Major surgery:Major surgery (excluding vascular access surgery) within the prior 8 weeks, during the Week -4 Screening phase or planned during the study.
    19.Transfusion:Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study.
    20.GI Bleeding:Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
    21.Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).
    22.Malignancy:Subjects with a history of malignancy within the prior 5 years, who receiving treatment for cancer, or who have a strong family history of cancer (e.g., familial cancer disorders); with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated prior to Week -4 Screening through Day 1 (randomization).
    Concomitant medication and other IP-related criteria
    23.Severe allergic reactions:History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product
    24.Drugs and supplements:Use of any prescription or non-prescription drugs or dietary supplements that are prohibited (see Section 5.7.2 for details) from Week -4 Screening until the Follow-up Visit.
    25.Prior investigational product exposure:The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Week -4 Screening through Day 1 (randomization).
    Generalhealth-relatedcriteria
    26.Other Conditions:Any other condition, clinical or laboratory abnormality, or examination finding that the Investigator and/or the medical monitor consider would put the subject at unacceptable risk.
    27.Pregnancy or Lactation:Pregnant females as determined by positive serum hCG test OR women who are lactating at Week -4 Screening or during the trial.
    Refer to protocol (page 27) for other Eligibility Criteria Considerations
    Criterios relacionados con la NC:
    1. Modalidad de diálisis: cambio previsto de la HD por la diálisis peritoneal dentro del periodo del estudio.
    2. Trasplante renal: trasplante renal preventivo o programado.
    3. Dosis alta de rhEPO: dosis de epoetina de >=360 UI/kg/semana por vía IV o dosis de darbepoetina de >=1,8 µg/kg/sem. por vía IV en las 8 sem. previas y hasta el día 1 (aleatorización).
    4. Mircera: uso de Mircera en las 8 sem. previas y hasta el día 1.
    Criterios basados en análisis clínicos (solo verificación en la sem.4):
    5. Vitamina B12: igual o inferior al límite inferior del intervalo de referencia (se puede repetir la selección al cabo de un mínimo de 8 sem).
    6. Folato: <2,0 ng/ml.
    7. Ferritina: <100 ng/ml.
    8. Saturación de transferrina (SATT): fuera del intervalo de referencia.
    Criterios relacionados con enfermedades cardiovasculares:
    9. Infarto de miocardio o síndrome coronario agudo: en las 8 sem. previas a la selección y hasta el día 1.
    10. Ictus o accidente isquémico transitorio: en las 8 sem. previas a la selección de la sem. 4 y hasta el día 1.
    11. Insuficiencia cardíaca:
    - Insuficiencia cardiaca de clase III/IV, según el sistema de clasificación funcional de la NYHA, diagnosticada antes de la selección de la sem. 4 y hasta el día 1.
    - Insuficiencia cardiaca derecha sintomática, diagnosticada antes de la selección de la sem. 4 y hasta el día 1.
    12. Hipertensión: definida por unos valores previos a la diálisis (sem. 4, día 1) de PAD >100 mm Hg o PAS >170 mm Hg.
    13. Enfermedad trombótica: antecedentes de enfermedad trombótica, excepto trombosis de vías vasculares, en las 8 sems. previas a la selección de la sem. 4 y hasta el día 1.
    Criterios relacionados con otras enfermedades:
    14. Enfermedad oftalmológica: cumplimiento de cualquier criterio de exclusión oftalmológico en la exploración ocular de la selección, como se describe en la sección 11.6.
    15. Enfermedad inflamatoria: enfermedad inflamatoria crónica activa, capaz de influir en la eritropoyesis, diagnosticada antes de la selección de la sem. 4 y hasta el día 1.
    16. Enfermedad hematológica: cualquier enfermedad hematológica, incluidas las de las plaquetas, los leucocitos y los eritrocitos, trastornos de la coagulación o cualquier otra causa de anemia, distinta de la nefropatía, diagnosticada antes de la selección de la sem. 4 y hasta el día 1.
    17. Hepatopatía: hepatopatía actual, anomalías hepáticas o biliares conocidas (a excepción del síndrome de Gilbert o la colelitiasis asintomática) o indicios de anomalías en las pruebas de función hepática de la selección (ALT o AST >,0 x LSN o bilirrubina total >1,5 x LSN), u otras anomalías hepáticas que, en opinión del investigador, impidan la participación del paciente en el estudio.
    NOTA: Los sujetos con hepatitis B o hepatitis C son elegibles siempre que no se cumplan estos criterios de exclusión.
    18. Cirugía mayor: cirugía mayor (excluida la de accesos vasculares) en las 8 sem. previas, durante la fase de selección de la sem. 4 o programada durante el estudio.
    19. Transfusión: transfusión de sangre en las 8 sem. previas, durante la fase de selección de la sem. 4 o prevista en algún momento durante el estudio.
    20. Hemorragia digestiva: indicios de úlcera péptica, duodenal o esofágica sangrante activa O BIEN hemorragia digestiva clínicamente importante en las 8 sem. previas a la selección de la sem. 4 y hasta el día 1.
    21. Infección aguda: signos clínicos de infección aguda o antecedentes de infección con necesidad de antibióticos IV en las 8 ssem. previas a la selección de la sem. 4 y hasta el día 1.
    NOTA: se permiten los antibióticos IV como profilaxis.
    22. Tumores malignos: sujetos con antecedentes de tumores malignos en los 5 años previos, en tratamiento antineoplásico o con marcados antecedentes familiares de cáncer, a excepción del carcinoma espinocelular o basocelular de la piel que se haya tratado definitivamente antes de la selección de la sem. 4 y hasta el día 1.
    Medicación concomitante y otros criterios relacionados con el PEI:
    23. Reacciones alérgicas graves: antecedentes de reacción alérgica o anafiláctica grave, o de hipersensibilidad a los excipientes del producto en investigación (véase en el MI de GSK1278863 la lista de excipientes [documento de GlaxoSmithKline número RM2008/00267/05]).
    24. Medicamentos y suplementos: uso de cualquier fármaco, de venta con o sin receta, o suplemento alimentario que esté prohibido (véanse los detalles en la sección 5.7.2) desde la selección de la sem. 4 hasta la visita de seguimiento.
    25. Exposición previa a productos en investigación: el sujeto ha participado en un ensayo clínico y ha recibido un producto en investigación en los 30 días previos a la selección de la sem. 4 y hasta el día 1.
    Criterios generales relacionados con la salud:
    (ver Sección 4.5 Criterios de exclusión del Protocol para más detalle).
    E.5 End points
    E.5.1Primary end point(s)
    Hemoglobin change from baseline at Week 4
    Variación de la Hb entre el valor basal y la semana 4.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 4
    Semana 4
    E.5.2Secondary end point(s)
    - Hgb change from baseline at Week 24
    - Percentage of time within, below, and above target range between Week 20 and 24
    - Number (%) of subjects with Hgb in the target range at Week 24
    - Change from baseline in hepcidin, ferritin, transferrin, transferrin saturation, total iron, total iron binding capacity (TIBC), reticulocyte Hgb (CHr), %hypochromic red blood cells (RBCs) at Week 24
    - Change from baseline in hematocrit, RBC, reticulocyte number at Week 24
    - Maximum observed change from baseline in EPO
    - Maximum observed change from baseline in VEGF
    - Population plasma PK parameters of GSK1278863 and metabolites
    - Incidence and severity of adverse events (AE)s and serious AEs (SAEs)
    - Reasons for discontinuation of study drug
    - Discontinuation for safety-related reasons, e.g. pre-specified stopping criteria or AE
    - Absolute values and changes from baseline in laboratory parameters, systolic pulmonary artery pressure (sPAP) left ventricular ejection fraction (LVEF), ophthalmology assessments, and vital signs
    - Preliminary assessment of major adverse cardiovascular events (MACE) and other cardiovascular (CV) events
    - Variación de la Hb entre el valor basal y la semana 24.
    - Porcentaje de tiempo dentro, por debajo y por encima del intervalo deseado entre las semanas 20 y 24
    - Número (%) de sujetos con Hb en el intervalo deseado en la semana 24
    - Número (%) de sujetos que alcanzan los criterios predefinidos de interrupción basados en la Hb
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 24
    Semana 24.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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 Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Será abierto a partir de la semana 4.
    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
    Double blind for GSK1278863 arms and open for Control arm from Week 4 onwards
    E.8.2.4Number of treatment arms in the trial6
    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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    Japan
    Korea, Republic of
    Russian Federation
    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
    GSK is not providing specific post-study treatment.
    The investigator is responsible for ensuring that consideration has been given to the post-study care of the patient?s medical condition
    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 months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 76
    F.4.2.2In the whole clinical trial 176
    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)
    GSK is not providing specific post-study treatment.
    The investigator is responsible for ensuring that consideration has been given to the post-study care of the patient's medical condition
    GSK no suministrará ningún tratamiento específico después del estudio. El investigador es el responsable de garantizar que se tenga en cuenta la atención de la enfermedad del paciente después del estudio.
    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 Decision2013-12-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-11-20
    P. End of Trial
    P.End of Trial StatusCompleted
    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
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA