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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2022-001634-10
    Sponsor's Protocol Code Number:SARO.21.001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-10-13
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2022-001634-10
    A.3Full title of the trial
    A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2b/3 Study to Evaluate the Efficacy and Safety of Saroglitazar Magnesium in Subjects with Primary Biliary Cholangitis.
    Estudio de fase 2b/3, multicéntrico, aleatorizado, doble ciego y controlado con placebo para evaluar la eficacia y la seguridad del saroglitazar magnésico en sujetos con colangitis biliar primaria.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study to Evaluate Safety, Tolerability and Efficacy in patients with Primary Biliary Cholangitis of Saroglitazar Magnesium-III (EPICS-III).
    Estudio para evaluar la seguridad, tolerabilidad y eficacia del saroglitazar magnésico en pacientes con colangitis biliar primaria-III (Study to Evaluate Safety, Tolerability and Efficacy in patients with Primary Biliary Cholangitis of Saroglitazar Magnesium-III).
    (EPICS-III)
    A.3.2Name or abbreviated title of the trial where available
    EPICS-III
    A.4.1Sponsor's protocol code numberSARO.21.001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05133336
    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 SponsorZydus Therapeutics Inc.
    B.1.3.4CountryUnited States
    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 supportZydus Therapeutics Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAdknoma Health Research, S.L.
    B.5.2Functional name of contact pointMarta
    B.5.3 Address:
    B.5.3.1Street AddressCapitán Haya, 1 Planta 16
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28020
    B.5.3.4CountrySpain
    B.5.4Telephone number+34932066666
    B.5.5Fax number932066667
    B.5.6E-mailregulatory@adknoma.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/21/2460
    D.3 Description of the IMP
    D.3.1Product nameSaroglitazar Magnesium 1 mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSAROGLITAZAR MAGNESIUM
    D.3.9.1CAS number 1639792203
    D.3.9.2Current sponsor codeSAROGLITAZAR MAGNESIUM
    D.3.9.3Other descriptive nameSAROGLITAZAR MAGNESIUM
    D.3.9.4EV Substance CodeSUB189079
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(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 RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Saroglitazar Magnesium 2 mg
    D.2.1.1.2Name of the Marketing Authorisation holderSaroglitazar Magnesium 2 mg
    D.2.1.2Country which granted the Marketing AuthorisationIndia
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/21/2460
    D.3 Description of the IMP
    D.3.1Product nameSaroglitazar Magnesium 2 mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSAROGLITAZAR MAGNESIUM
    D.3.9.1CAS number 1639792203
    D.3.9.2Current sponsor codeSAROGLITAZAR MAGNESIUM
    D.3.9.3Other descriptive nameSAROGLITAZAR MAGNESIUM
    D.3.9.4EV Substance CodeSUB189079
    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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    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
    Primary biliary Cholangitis
    Colangitis biliar primaria
    E.1.1.1Medical condition in easily understood language
    Primary biliary cholangitis or primary biliary cirrhosis
    Colangitis biliar primaria o cirrosis biliar primaria
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10080429
    E.1.2Term Primary biliary cholangitis
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate superiority of Saroglitazar Magnesium Optimal Dose (1 or 2 mg) dosed once daily relative to Placebo with respect to biochemical response based on the composite endpoints of ALP and total bilirubin at Week 52 in subjects with PBC.
    Demostrar la superioridad de la dosis óptima de saroglitazar magnésico (1 o 2 mg) administrada una vez al día respecto a un placebo en cuanto a la respuesta bioquímica según los criterios de valoración combinados de FA y bilirrubina total en la semana 52 en sujetos con CBP.
    E.2.2Secondary objectives of the trial
    1. To evaluate the effect of Saroglitazar Magnesium 1 mg/Optimal Dose (1 or 2 mg)and Saroglitazar Magnesium 2 mg/Optimal Dose (1 or 2 mg) relative to Placebo with respect to biochemical response based on the composite endpoints of ALP and total bilirubin at Weeks 4, 8, 16, and 24.
    2. To evaluate the effect of Saroglitazar Magnesium Optimal Dose (1 or 2 mg) relative to Placebo with respect to change from baseline in ALP at Weeks 24 and 52.
    3. To evaluate the effect of Saroglitazar Magnesium Optimal Dose (1 or 2 mg) relative to Placebo with respect to improvement in liver stiffness measurement (LSM) of at least 25% at Weeks 24 and 52 relative to baseline assessed by FibroScan®.
    4. To evaluate the effect of Saroglitazar Magnesium 1 mg/Optimal Dose (1 or 2 mg) and Saroglitazar Magnesium 2 mg/Optimal Dose (1 or 2 mg) relative to Placebo at Weeks 16, 24, and 52.
    ...........
    1.Evaluar el efecto de saroglitazar magnésico 1 mg/dosis óptima (1 o 2 mg) y saroglitazar magnésico 2 mg/dosis óptima (1 o 2 mg) en comparación con un placebo con respecto a la respuesta bioquímica según los criterios de valoración combinados de FA y bilirrubina total en las semanas 4, 8, 16 y 24.
    2.Evaluar el efecto de la dosis óptima de saroglitazar magnésico (1 o 2 mg) en comparación con un placebo en cuanto a la variación de la FA entre el momento basal y las semanas 24 y 52.
    3.Evaluar el efecto de la dosis óptima de saroglitazar magnésico (1 o 2 mg) en comparación con un placebo en cuanto a una mejoría de la medición de la rigidez hepática (MRH) ≥25 % entre el momento basal y las semanas 24 y 52, determinada mediante FibroScan®.
    4. Evaluar el efecto de saroglitazar magnésico 1 mg/dosis óptima (1 o 2 mg) y saroglitazar magnésico 2 mg/dosis óptima (1 o 2 mg) en comparación con un placebo en las semanas 16, 24 y 52 sobre los siguientes parámetros:
    • ............
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males or females, between 18 and 75 years of age, both inclusive at screening.
    2. Subjects on ursodeoxycholic acid (UDCA) for at least 12 months at a therapeutic dose (at least 13 mg/kg per day) and a stable dose for 6 months prior to Screening Visit and having ALP ≥ 1.67 x ULN.
    OR
    Subjects who are unable to tolerate UDCA and did not receive UDCA for at least 3 months prior to the date of screening and having ALP ≥ 1.67 x ULN.
    3. History of confirmed PBC diagnosis, based on American Association for the Study of Liver Disease [AASLD] and European Association for Study of the Liver [EASL] Practice Guidelines, as demonstrated by the presence of at least ≥ 2 of the following 3 diagnostic factors:
    -History of elevated ALP levels for at least 6 months prior to screening
    -The subjects should have positive anti-mitochondrial antibodies (AMA) titer OR if AMA is negative or in low titer (< 1:80), then the subjects should have PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
    -Liver biopsy consistent with PBC
    4. ALP ≥ 1.67 x ULN at both Visits 1 and 2 and with < 30% variance between the levels from Visit 1 to Visit 2
    5. Total bilirubin < 2 x ULN at screening (Visit 1)
    6. Must provide written informed consent and agree to comply with the trial protocol.
    1.Varones o mujeres de entre 18 y 75 años, ambos inclusive, en la visita de selección.
    2.Sujetos tratados con ácido ursodesoxicólico (AUDC) durante al menos 12 meses en una dosis terapéutica (≥13 mg/kg al día) y una dosis estable durante 6 meses antes de la visita de selección y con una FA ≥1,67 veces el LSN.
    O
    Sujetos que no toleren el AUDC y no lo hayan recibido durante al menos 3 meses antes de la fecha de selección y con una FA ≥1,67 veces el LSN.
    3.Antecedentes de diagnóstico confirmado de CBP, según las directrices prácticas de la American Association for the Study of Liver Disease (AASLD) y la Asociación Europea para el Estudio del Hígado (EASL), demostrado por la presencia de al menos 2 de los 3 factores diagnósticos siguientes:
    • Antecedentes de concentración elevada de FA durante al menos 6 meses antes de la selección.
    • Título positivo de anticuerpos antimitocondriales (AMA) O , en caso de AMA negativos o a título bajo (<1:80), presencia de anticuerpos específicos de la CBP (anti-GP210, anti-SP100 o anticuerpos contra los componentes principales de M2 [PDC-E2, complejo 2-oxoglutarato deshidrogenasa]).
    • Biopsia hepática compatible con CBP.
    4.FA ≥1,67 veces el LSN en las visitas 1 y 2 con una variación <30 % entre las concentraciones de las visitas 1 y 2.
    5.Bilirrubina total <2 veces el LSN en la visita de selección (visita 1).
    6.El sujeto debe otorgar su consentimiento informado por escrito y comprometerse a cumplir el protocolo del ensayo.
    E.4Principal exclusion criteria
    1.Consumption of 2 standard alcohol drinks per day if male and 1 standard alcohol drink per day if female for at least 3 consecutive months (12 consecutive weeks) within 5 year before screening. 2.History or presence of other concomitant liver diseases at screening: a.Chronic hepatitis B or C virus (HBV, HCV) infection. b.Primary sclerosing cholangitis (PSC). c.Alcoholic liver disease. d.Autoimmune hepatitis (AIH) indicative of PBC with overlap syndrome. e.Hemochromatosis. f.Non-alcoholic steatohepatitis (NASH) on historical biopsy. 3.Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, encephalopathy, known large esophageal varices or history of variceal bleeding and active or history of hepatorenal syndrome at screening. 4.Clinically silent compensated cirrhosis (at screening), defined as (a) nodular liver contour by abdominal imaging with at least one sign of liver dysfunction (> ULN INR or < LLN serum albumin); or (b) prolonged INR (> ULN) and diminished albumin (< LLN); or (c) platelet count <140x109/L with INR > ULN or serum albumin < LLN. 5.Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers. 6.Use of thiazolidinediones or fibrates (within 12 weeks prior to screening) 7.Use of obeticholic acid (OCA), azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (Note: Prednisone dose should not be more than 10 mg per day); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin) (within 12 weeks prior to screening) 8.Use of drugs that are known cytochromes P2C8 (CYP2C8) inhibitors/substrate within 4 weeks prior to screening (refer to Appendix 7 for List of Known CYP2C8 Inhibitors/Substrate).
    9. History of bowel surgery (gastrointestinal [bariatric] surgery in the preceding 1 year or undergoing evaluation for gastrointestinal surgery (bariatric surgery for obesity, extensive small-bowel resection) or orthotopic liver transplant (OLT) or listed for OLT. 10.Type 1 diabetes mellitus
    11. Unstable cardiovascular disease, including: a. Unstable angina, (i.e., new or worsening symptoms of coronary heart disease in the 12 weeks before screening and throughout the Screening Period), acute coronary syndrome in the 24 weeks before screening and throughout the Screening Period, acute myocardial infarction in the 12 weeks before screening and throughout the Screening Period or heart failure of New York Heart Association class (III to IV) or worsening congestive heart failure, or coronary artery intervention, in the 24 weeks before screening and throughout the Screening Period. b. History/current unstable cardiac dysrhythmias. c. Uncontrolled hypertension at screening. d. Stroke or transient ischemic attack in the 24 weeks before screening. 12. History of intracranial hemorrhage, arteriovenous malformation, bleeding disorder, coagulation disorders, or screening blood tests that, in the opinion of the Investigator, indicate altered coagulability (e.g., PT, INR, aPTT) at screening. 13. An uncontrolled thyroid disorder a. Uncontrolled hyperthyroidism: defined as any history of hyperthyroidism that has either not been treated with either radioactive iodine and/or surgery or that has been treated with radioactive iodine and/or surgery, but has required ongoing continuous or intermittent use of thyroid hormone synthesis inhibitors (i.e., methimazole or propylthiouracil) in the 24 weeks before screening b. Uncontrolled hypothyroidism: defined as initiation of thyroid hormone replacement therapy or dose adjustment of replacement therapy in the 12 weeks before screening. 14. History of myopathies or evidence of active muscle disease demonstrated by CPK ≥ 5 x ULN at screening. 15. Subjects whose ALT, AST, or ALP exceeds by more than 50% on Visit 2 reading compared to Visit 1. Note: If the ALT, AST or ALP values on Visit 2 exceed by more than 50% from Visit 1, then a third value will be measured (within 1- 2 weeks) to assess for the trend. If the third value shows continued increase ≥ 10%, then subject is considered ineligible for randomization.
    16. Any of the following laboratory values at screening: a. Platelets < 100 × 109/L b. Albumin < 3.2 g/dL c. eGFR < 60 mL/min/1.73 m2 d. ALP > 10 x ULN e. ALT or AST > 250 U/L. 17. Participation in another interventional clinical study and receipt of any other investigational medication (within 12 weeks prior to randomization up to end of study). 18. History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial non-melanoma skin cancer. 19. Contraindications to Saroglitazar Magnesium or has any conditions affecting the ability to evaluate the effects of Saroglitazar Magnesium......
    1. Consumo de 2 unidades de bebida estándar al día en los varones y de 1 unidad de bebida estándar al día en las mujeres durante al menos 3 meses consecutivos (12 semanas consecutivas) en los 5 años previos a la selección (Nota: 1 unidad = 360 ml de cerveza, 120 ml de vino o 30 ml de licores fuertes).
    2. Antecedentes o presencia de otras hepatopatías concomitantes en el período de selección:
    a. Infección crónica por el virus de la hepatitis B o C (VHB o VHC).
    (Nota: Sin embargo, si el sujeto ha recibido tratamiento contra la infección por el VHC y ha mostrado curación durante más de 2 años antes de la selección, podrá participar en el estudio).
    b. Colangitis esclerosante primaria (CEP).
    c. Hepatopatía alcohólica.
    d. Hepatitis autoinmunitaria (HAI) indicativa de CBP con síndrome de solapamiento.
    Nota: Habitualmente se utilizan los criterios de París para definir la presencia de CBP con características de HAI, que han sido avalados por la EASL y la AASLD. Según estos criterios, puede establecerse el diagnóstico de CBP de la manera siguiente:
    Al menos dos de las características siguientes:
    I. FA >2 veces el LSN o GGT >5 veces el LSN.
    II. AMA >1:40.
    III. Lesión florida de las vías biliares en el examen histológico.
    Y
    Al menos dos de las tres características siguientes:
    I. ALT >5 veces el LSN.
    II. Concentración sérica de inmunoglobulina G >2 veces el LSN o autoanticuerpos contra el músculo liso positivos.
    III. Hepatitis de la zona de interfase moderada o grave en el examen histológico.
    e. Hemocromatosis.
    f. Esteatohepatitis no alcohólica (EHNA) en una biopsia histórica.
    3. Cirrosis con complicaciones, incluidos antecedentes o presencia de peritonitis bacteriana espontánea, carcinoma hepatocelular, ascitis, encefalopatía o varices esofágicas grandes conocidas, antecedentes de hemorragia por varices o síndrome hepatorrenal activo o previo en el período de selección.
    4. Cirrosis compensada clínicamente asintomática, definida como: (a) contorno hepático nodular en estudios de imagen abdominales con al menos un signo de disfunción hepática (INR >LSN o albúmina sérica <LIN), (b) prolongación del INR (>LSN) y disminución de la albúmina (<LIN) o (c) recuento de plaquetas <140 x 109/l con INR >LSN o albúmina sérica <LIN.
    5. Enfermedades que puedan causar aumentos extrahepáticos de la FA (p. ej., enfermedad de Paget) o que puedan reducir la esperanza de vida a menos de 2 años, incluidos cánceres conocidos.
    6. Uso de tiazolidinadionas o fibratos (en las 12 semanas previas a la selección).
    7. Uso de ácido obeticólico (AOC), azatioprina, ciclosporina, metotrexato, micofenolato, pentoxifilina, budesonida y otros corticosteroides sistémicos (Nota: La dosis de prednisona no debe ser superior a 10 mg al día) o de fármacos potencialmente hepatotóxicos (como α-metildopa, ácido valproico sódico, isoniazida o nitrofurantoína) (en las 12 semanas previas a la selección).
    8. Uso de fármacos que sean inhibidores o sustratos conocidos del citocromo P2C8 (CYP2C8) en las 4 semanas previas a la selección (consulte en el apéndice 7 la lista de inhibidores y sustratos conocidos del CYP2C8).
    9. Antecedentes de cirugía intestinal (cirugía gastrointestinal [bariátrica] en el año anterior o en fase de evaluación para someterse a cirugía gastrointestinal (cirugía bariátrica por obesidad, resección extensa del intestino delgado) o a un trasplante ortotópico de hígado (TOH) o en lista de espera para TOH.
    10. Diabetes mellitus de tipo 1.
    11. Enfermedad cardiovascular inestable, como:
    a. Angina de pecho inestable (es decir, aparición o empeoramiento de síntomas de cardiopatía coronaria en las 12 semanas previas a la selección y durante todo el período de selección), síndrome coronario agudo en las 24 semanas previas a la selección y durante todo el período de selección, infarto agudo de miocardio en las 12 semanas previas a la selección y durante todo el período de selección o insuficiencia cardíaca en clase III o IV de la New York Heart Association, empeoramiento de la insuficiencia cardíaca congestiva o intervención sobre las arterias coronarias en las 24 semanas previas a la selección y durante todo el período de selección.
    b. Antecedentes o presencia de arritmias cardíacas inestables.
    c. Hipertensión no controlada en el período de selección.
    d. Ictus o accidente isquémico transitorio en las 24 semanas previas a la selección.
    12. Antecedentes de hemorragia intracraneal, malformación arteriovenosa, trastorno hemorrágico, trastornos de la coagulación o análisis de sangre de selección que, en opinión del investigador, indiquen una alteración de la coagulabilidad (p. ej., TP, INR o TTPa) en el período de selección.
    13. Trastorno tiroideo no controlado.
    ...................
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects with biochemical response based on the composite endpoints of ALP and total bilirubin [ALP < 1.67 x ULN, ≥ 15% decrease in ALP relative to baseline, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in patients with known Gilbert’s syndrome] at Week 52.
    Proporción de sujetos con respuesta bioquímica según los criterios de valoración combinados de FA y bilirrubina total (FA <1,67 veces el LSN, disminución ≥15 % de la FA con respecto al momento basal y bilirrubina total ≤LSN o bilirrubina directa ≤LSN en pacientes con síndrome de Gilbert conocido) en la semana 52.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 52
    Semana 52
    E.5.2Secondary end point(s)
    1. Proportion of subjects with biochemical response based on the composite endpoints of ALP and total bilirubin [ALP < 1.67 x ULN, ≥ 15% decrease in ALP, and total bilirubin ≤ ULN or direct bilirubin ≤ ULN in patients with known Gilbert’s syndrome] at Weeks 4, 8, 16, and 24.
    -Proportion of subjects with ALP improvement of at least 15%, 30%, 40%, and 50% at Weeks 24 and 52.
    -Change and percent change from baseline in ALP at Weeks 24 and 52.
    -Proportion of subjects with complete normalization of ALP at Weeks 24 and 52.
    -Proportion of subjects with decrease in LSM of at least 25% from baseline to Weeks 24 and 52.
    -Change from baseline in liver enzyme parameters (ALT, AST, GGT, total bilirubin and albumin) at Weeks 16, 24, and 52.
    -Change from baseline in lipid parameters (TG, LDL-C, HDL-C, VLDL-C, total cholesterol, and non-HDL-C) at Weeks 24 and 52.
    -Change from baseline in serum bile acids at Weeks 24 and 52.
    -Change from baseline in 5-D itch scale at Weeks 4, 8, 16, 24, and 52.
    -Change from baseline in quality of life (PBC 40) questionnaire domains at Weeks 16, 24 and 52.
    -Change from baseline in PGIC scale at Weeks 4, 8, 16, 24, and 52.
    -Change from baseline in PGTB scale at Weeks 4, 8, 16, 24, and 52.
    -Change from baseline in PGIWIS scale at Weeks 4, 8, 16, 24, and 52.
    -Frequency and severity of AEs and SAEs
    -Frequency of AE of special interest (AESI): drug-induced liver injury (DILI)
    -Clinical laboratory testing (hematology, biochemistry, and urinalysis)
    -Vital signs
    -Body weight
    -12-lead electrocardiogram (ECG)
    -Physical examination
    1.Proporción de sujetos con respuesta bioquímica según los criterios de valoración combinados de FA y bilirrubina total (FA <1,67 veces el LSN, disminución ≥15 % de la FA y bilirrubina total ≤LSN o bilirrubina directa ≤LSN en pacientes con síndrome de Gilbert conocido) en las semanas 4, 8, 16 y 24.
    • Proporción de sujetos con una mejoría de la FA ≥15 %, 30 %, 40 % y 50 % en las semanas 24 y 52.
    • Variación y variación porcentual de la FA entre el momento basal y las semanas 24 y 52.
    • Proporción de sujetos con normalización completa de la FA en las semanas 24 y 52.
    • Proporción de sujetos con una disminución de la MRH ≥25 % entre el momento basal y las semanas 24 y 52.
    • Variación de los parámetros de enzimas hepáticas (ALT, AST, GGT, bilirrubina total y albúmina) entre el momento basal y las semanas 16, 24 y 52.
    • Variación de los parámetros lipídicos (TG, C-LDL, C-HDL, C-VLDL, colesterol total y C-no HDL) entre el momento basal y las semanas 24 y 52.
    • Variación de los ácidos biliares séricos entre el momento basal y las semanas 24 y 52.
    • Variación de la escala de prurito 5-D entre el momento basal y las semanas 4, 8, 16, 24 y 52.
    • Variación de los dominios del cuestionario de calidad de vida PBC 40 entre el momento basal y las semanas 16, 24 y 52.
    • Variación de la escala PGIC entre el momento basal y las semanas 4, 8, 16, 24 y 52.
    • Variación de la escala PGTB entre el momento basal y las semanas 4, 8, 16, 24 y 52.
    • Variación de la escala PGIWIS entre el momento basal y las semanas 4, 8, 16, 24 y 52.
    • Frecuencia e intensidad de los AA y AAG.
    • Frecuencia del AA de interés especial (AAIE): lesión hepática farmacógena (LHF).
    • Análisis clínicos (hematología, bioquímica y análisis de orina).
    • Constantes vitales.
    • Peso corporal.
    • Electrocardiograma (ECG) de 12 derivaciones.
    • Exploración física.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 4, 8, 16, 24, and 52
    Semanas 4,8,16,24 y 52
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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) 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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States No
    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
    Argentina
    Colombia
    United States
    Iceland
    Italy
    Turkey
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months15
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months15
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 60
    F.4.2.2In the whole clinical trial 192
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Ninguno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-01-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-10-26
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA