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    Summary
    EudraCT Number:2011-004728-36
    Sponsor's Protocol Code Number:747-301
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-03-05
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2011-004728-36
    A.3Full title of the trial
    A Phase 3, Double Blind, Placebo Controlled Trial and Long Term Safety Extension of Obeticholic Acid in Patients with Primary Biliary Cirrhosis
    Studio di fase 3, in doppio cieco, controllato con placebo ed estensione per la sicurezza a lungo termine dell'acido obeticolico in pazienti affetti da cirrosi biliare primitiva
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of Obeticholic Acid versus Placebo in Patients with Primary Biliary Cirrhosis plus long term extension study only with Obeticholic Acid
    Uno studio di acido obeticolico versus placebo in pazienti con Cirrosi biliare primitiva piu' studio di estensione a lungo termine con soltanto acido obeticolico
    A.3.2Name or abbreviated title of the trial where available
    A study of OCA in Patients with Primary Biliary Cirrhosis
    Uno studio di OCA in pazienti con CPB
    A.4.1Sponsor's protocol code number747-301
    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 SponsorINTERCEPT PHARMACEUTICALS, 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 supportIntercept Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAccelsior CRO and Consultancy Services
    B.5.2Functional name of contact pointInformazione sulla sperimentazione
    B.5.3 Address:
    B.5.3.1Street Address50
    B.5.3.2Town/ cityBudapest
    B.5.3.3Post code1147
    B.5.3.4CountryHungary
    B.5.4Telephone number36 1 2990091
    B.5.5Fax number36 1 2990096
    B.5.6E-mailclinicaltrials@accelsior.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/3/10/753
    D.3 Description of the IMP
    D.3.1Product nameOCA (INT-747)
    D.3.2Product code OCA (INT-747)
    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 INNAcido Obeticolico
    D.3.9.1CAS number 459789-99-2
    D.3.9.2Current sponsor codeOCA, 6-ECDCA o INT-747
    D.3.9.3Other descriptive nameObeticholic Acid
    D.3.9.4EV Substance CodeNA
    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: 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 Yes
    D.2.5.1Orphan drug designation numberEU/3/10/753
    D.3 Description of the IMP
    D.3.1Product nameOCA (INT-747)
    D.3.2Product code OCA (INT-747)
    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 INNAcido Obeticolico
    D.3.9.1CAS number 459789-99-2
    D.3.9.2Current sponsor codeOCA, 6-ECDCA o INT-747
    D.3.9.3Other descriptive nameObeticholic Acid
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/10/753
    D.3 Description of the IMP
    D.3.1Product nameOCA (INT-747)
    D.3.2Product code OCA (INT-747)
    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 INNAcido Obeticolico
    D.3.9.1CAS number 459789-99-2
    D.3.9.2Current sponsor codeOCA, 6-ECDCA o INT-747
    D.3.9.3Other descriptive nameObeticholic Acid
    D.3.9.4EV Substance CodeNA
    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.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 cirrhosis
    Cirrosi Biliare Primitiva
    E.1.1.1Medical condition in easily understood language
    Primary biliary cirrhosis (PBC) is a rare, chronic, autoimmune liver disease characterized by both liver and biliary tract lesions that progresses to cirrhosis and other complications.
    La Cirrosi Biliare Primaria è una malattia del fegato,cronica,rara,autoimmune,caratterizzata da lesioni del fegato e vie biliari che progredisce verso la cirrosi e altre complicazioni.
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level SOC
    E.1.2Classification code 10019805
    E.1.2Term Hepatobiliary disorders
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the effects of OCA in patients with PBC on: -Serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint -Safety
    Valutare gli effetti di OCA nei pazienti con CBP su: - Fosfatasi alcalina nel siero (ALP) e bilirubina totale, insieme come end point composito - Sicurezza
    E.2.2Secondary objectives of the trial
    To assess the effects of OCA in patients with PBC on: -Hepatocellular injury and liver function, including histology (inflammatory, structural [portal, parenchymal] and fibrotic assessments) -Disease specific symptoms -Biomarkers and noninvasive assessments of liver fibrosis -Bile acids (BA) -Other exploratory evaluations
    Valutare gli effetti di OCA nei pazienti con CBP su: - Lesione epatocellulare e funzionalità epatica, inclusa istologia (valutazioni infiammatorie, strutturali [portale, parenchimale] e fibrotiche) - Sintomi specifici della patologia - Biomarcatori e valutazioni non invasive della fibrosi epatica - Acidi biliari - Altre valutazioni esplorative
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    OTHER SUBSTUDIES:
    Optional Genetics Research Study (A Phase 3, Double Blind, Placebo Controlled Trial and Long Term Safety Extension of Obeticholic Acid in Patients with Primary Biliary Cirrhosis) To study genes that may be involved in the development of Primary Biliary Cirrhosis (PBC) disease (and related conditions).

    ALTRI SOTTOSTUDI:
    Uno studio di ricerca genetica opzionale(studio di fase 3 con OCA in pazienti con CBP).Per studiare i geni che possono essere coinvolte nello sviluppo della CBP (e le condizioni correlati).

    E.3Principal inclusion criteria
    1. Definite or probable PBC diagnosis (consistent with AASLD and EASL Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors: -History of elevated ALP levels for at least 6 months prior to Day 0 -Positive AMA titer or PBC specific antibodies -Liver biopsy consistent with PBC 2. At least 1 of the following qualifying biochemistry values: XML File Identifier: NSspYvB4+bFIdSKGc1NeGyJcRB0= Page 18/30 - ALP≥1.67x ULN -Total bilirubin > ULN but < 2x ULN 3. Age ≥18 years 4. Taking UDCA for at least 12 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0 5. Contraception: Female patients of childbearing potential must use ≥1 effective (≤1% failure rate) method of contraception during the trial and until the End of Treatment (EOT) visit. 6. Must provide written informed consent and agree to comply with the trial protocol.
    1. Diagnosi sicura o probabile di PBC (coerente con le indicazioni sulle procedure corrette AASLD e EASL; [Lindor 2009; EASL 2009]), dimostrata dalla presenza di ≥ 2 dei 3 fattori diagnostici che seguono: - Anamnesi di livelli di ALP elevati per almeno 6 mesi prima del Giorno 0 - Titolazione di AMA positiva o anticorpi PBC specifici - Biopsia epatica coerente con la PBC 2. Almeno 1 dei seguenti valori biochimici qualificanti: - ALP ≥ 1,67x ULN - Bilirubina totale &gt; ULN ma &lt; 2x ULN 3. Età ≥ 18 anni 4. Assunzione di UDCA per almeno 12 mesi (dose fissa per ≥ 3 mesi) prima del Giorno 0 o impossibilità di tollerare UDCA (niente UDCA per ≥ 3 mesi) prima del Giorno 0 5. Contraccezione: le pazienti di sesso femminile in età fertile devono usare ≥ 1 metodo di contraccezione efficace (percentuale di fallimento ≤ 1%) durante la sperimentazione e fino alla visita di Termine del trattamento. 6. Devono fornire consenso informato scritto e accettare di rispettare il protocollo della sperimentazione.
    E.4Principal exclusion criteria
    Patients will be excluded from the trial if they meet any of the following: 1. History or presence of other concomitant liver diseases including: -Hepatitis B or C virus (HCV, HBV) infection -Primary sclerosing cholangitis (PSC) -Alcoholic liver disease -Definite autoimmune liver disease or overlap hepatitis -Nonalcoholic steatohepatitis (NASH) -Gilbert's Syndrome (exclusion due to interpretability of bilirubin levels) 2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including: -History of liver transplantation, current placement on a liver transplant list or current MELD score ≥ 15 -Portal hypertention and complications, including: known esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds or related interventions (e.g., insertion of variceal bands or transjugular intrahepatic portosystemic shunt [TIPS]), hepatic encephalopathy -Cirrhosis with complications, including history or presence of: spontaneous -Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L) bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN 3. Patients with a history of severe pruritus requiring current or prior systemic treatment (e.g., with bile acid sequestrants [BAS] or rifampicin) 4. Administration of the following medications is prohibited as specified below: -Prohibited 6 months prior to Day 0 and throughout the trial (i.e., to last dose and/or EOT): azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin) -Prohibited 12 months prior to Day 0 and throughout the trial (i.e., to last dose and/or EOT): antibodies or immunotherapy directed against interleukins or other cytokines or chemokines 5. Patients who have previously participated in a clinical trial of OCA will not be allowed to participate. 6. History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pretreatment) QT or QTc interval of > 500 milliseconds (msec). 7. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
    I pazienti saranno esclusi dalla sperimentazione se soddisfano uno qualsiasi dei criteri seguenti: 1. Anamnesi o presenza di altre patologie epatiche concomitanti, quali: - Infezione da virus dell'epatite B o C (HCV, HBV) - Colangite sclerosante primitiva (CSP) - Patologia alcolica del fegato - Patologia epatica autoimmune nota o epatite da sovrapposizione - Steatoepatite non alcolica (NASH) - Sindrome di Gilbert (esclusione dovuta all'interpretabilità dei livelli di bilirubina) 2. Presenza di complicanze cliniche della PBC o di scompenso epatico significativo dal punto di vista clinico, quali: - Anamnesi di trapianto epatico, attuale inserimento in una lista di attesa per trapianti di fegato o punteggio MELD ≥ 15 - Ipertensione o complicanze del portale, quali: varici esofagee note, ascite refrattaria ai diuretici o poco controllata, anamnesi di emorragie delle varici o interventi correlati (ad es.: inserimento di bendaggi delle varici o di shunt portosistemico intraepatico transgiugulare [TIPS]), encefalopatia epatica - Cirrosi con complicanze, inclusa anamnesi o presenza di: peritonite batterica spontanea, carcinoma epatocellulare, bilirubina &gt; 2x ULN - Sindrome epatorenale (tipo I o II) o controllo della creatinina del siero &gt; 2 mg/dl (178 μmol/l) 3. Pazienti con anamnesi di prurito grave che necessiti di trattamento sistemico precedente o attuale (ad es.: con sequestranti degli acidi biliari [BAS] o rifampicina) 4. La somministrazione dei farmaci seguenti è proibita secondo quanto indicato di seguito: - Proibito 6 mesi prima del Giorno 0 e per tutta la sperimentazione (ovvero fino all'ultimo dosaggio e/o alla visita di termine della sperimentazione):azatioprina,colchicina,ciclosporina,metotressato,micofenolato mofetile,pentossifillina, fenofibrato o altri fibrati, budesonide e altri corticosteroidi sistemici, farmaci potenzialmente epatotossici (quali alfa metildopa, acido sodio valproato, isoniazide o nitrofurantoina) - Proibito 12 mesi prima del Giorno 0 e per tutta la sperimentazione (ovvero fino all'ultimo dosaggio e/o alla visita di termine della sperimentazione): anticorpi o immunoterapia diretta con interleuchina o altri citochine o chemochine 5. I pazienti che hanno già partecipato a uno studio clinico con OCA non sono autorizzati a partecipare. 6. Anamnesi o presenza di aritmie cardiache preoccupanti dal punto di vista clinico o prolungamento del controllo (pretrattamento) dell'intervallo del QT o QTc &gt; 500 millisecondi (ms). 7. Per pazienti di sesso femminile: gravidanza nota o test di gravidanza urinario positivo (confermato da test di gravidanza del siero positivo) o in allattamento
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoint (evaluated as a responder analysis): ALP < 1.67x ULN and total bilirubin within normal limits (WNL), and ALP decrease of ≥ 15% (to exclude clinically insignificant ALP changes)
    Obiettivi principali: - ALP < 1,67x ULN e bilirubina totale nella norma (WNL), e - aumento dell'ALP ≥ 15% (per escludere variazioni non clinicamente significative dell'ALP)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Double blind phase : Screening(≤ -1 to-8 Wks), Day 0, W2, M3, M6, M9, M12/LTSE D1, End of Treatment (if applicable), follow-up Long term safety extension: M3, M6, M9, M12, End of Treatment, follow up
    Fase di doppio cieco: screening (≤ -1 a -8 settimane), Giorno 0, W2, M3, M6, M9, M12/LTSE D1, fine del trattamento (se applicabile),follow-up Fase di Estensione per la sicurezza a lungo termine: M3, M6, M9, M12, fine del trattamento, follow-up
    E.5.2Secondary end point(s)
    Analyses regarding secondary endpoints will be specified in the SAP and conducted for the following parameters. It is anticipated that additional disease prognostic algorithms will be published during the course of the trial. Where appropriate, secondary analyses will be conducted using such algorithms. At the blinded data review a determination will be made as to which algorithms will be evaluated statistically, as it is likely that there will be small numbers of patients for some algorithms and formal statistical analysis will not therefore be appropriate. • ALP response rates of 10%, 20% and 40% change • Disease Prognostic Risk (criteria in relevant patients): -ALP ≤ 3x ULN and AST ≤ 2x ULN and normal bilirubin - ALP ≤ 1.5x ULN and AST ≤ 1.5x ULN and bilirubin within normal limits - ALP ≤ 1.67x ULN and normal bilirubin - Normal bilirubin and normal albumin • Clinical laboratory values: - GGT, ALT, AST, total and conjugated bilirubin - Albumin, prothrombin time and INR • Liver biopsy/histology: Inflammatory, structural (portal, parenchymal) and fibrotic assessments • Disease Specific Symptoms: - PBC-40 - 5-D Pruritus Questionnaire - Pruritus VAS • Biomarkers and non-invasive assessments of liver fibrosis - Fibrosis biomarkers (ELF) - TE (at selected trial sites) - Other analytes: TNF-α, TGF-β, IL-6, CK-18 and lysophosphatidic acid • Bile acids - Plasma OCA, other bile acids and conjugate concentrations - Bile and feces concentrations (at selected trial sites)
    Le analisi relative agli endpoint secondari saranno specificati nel SAP e condotte per i seguenti parametri. Si prevede che ulteriori algoritmi prognostici sulla malattia saranno pubblicati nel corso dello studio. Se del caso, le analisi secondarie saranno condotte utilizzando tali algoritmi. In sede di revisione in cieco dei dati si deciderà quali algoritmi saranno valutati statisticamente, in quanto è probabile che ci sarà un piccolo numero di pazienti per alcuni algoritmi e quindi un’ analisi statistica formale potrebbe non essere appropriata. • Tassi di risposta di variazione dell’ALP del 10%, 20% e 40%. • rischio prognostici di malattia (criterio rilevante in alcuni pazienti): - ALP ≤ 3x ULN e AST ≤ 2x ULN e bilirubina normale - ALP ≤ 1,5 x ULN e AST ≤ 1,5 x ULN e bilirubina entro i limiti normali - ALP 1.67x ≤ ULN e bilirubina normale - bilirubina normale e albumina normale • valori di laboratorio clinico: - GGT, ALT, AST, bilirubina totale e coniugata - L'albumina, tempo di protrombina e INR • biopsia epatica / istologia: valutazione dell’infiammazione della strutturali (portale, parenchimale) e della fibrosi. • sintomi specifici della malattia: - PBC-40 - Questionario 5-D sul Prurito - VAS sul Prurito • Biomarkers e valutazioni non invasive della fibrosi epatica - Biomarcatori della Fibrosi (ELF) - TE (in centri selezionati) - Altri analiti: TNF-α, TGF-β, IL-6, CK-18 e acido lisofosfatidico • acidi biliari - concentrazioni di OCA plasmatico e di altri acidi biliari nativi e coniugati - Concentrazioni nella bile e nelle feci (in centri selezionati)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Double blind phase : Screening(≤ -1 to-8 Wks), Day 0, W2, M3, M6, M9, M12/LTSE D1, End of Treatment (if applicable), follow-up Long term safety extension: M3, M6, M9, M12, End of Treatment, follow up
    Fase di doppio cieco: screening (≤ -1 a -8 settimane), Giorno 0, W2, M3, M6, M9, M12/LTSE D1, fine del trattamento (se applicabile),follow-up Fase di Estensione per la sicurezza a lungo termine: M3, M6, M9, M12, fine del trattamento, follow-up
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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
    Canada
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months0
    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.1.1Number of subjects for this age range: 0
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 180
    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)
    Follow up visit occurring 4 weeks (± 7 days) after receiving the last dose of study medication.
    Visita di controllo a 4 settimane (± 7 giorni) dopo aver ricevuto l'ultimo dose del farmaco in studio.
    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 Decision2012-03-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-24
    P. End of Trial
    P.End of Trial StatusCompleted
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