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    Summary
    EudraCT Number:2011-000078-80
    Sponsor's Protocol Code Number:PMR-EC-1207
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2012-08-06
    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 number2011-000078-80
    A.3Full title of the trial
    A Phase II, Parallel Group, Randomized, Multicentre, Open Label Study to Compare the Pharmacokinetics of Tacrolimus in De Novo Pediatric Allograft Recipients Treated with an Advagraf or Prograf Based Immunosuppressive Regimen, Including a Long-Term Follow-Up
    STUDIO DI FASE II, A GRUPPI PARALLELI, RANDOMIZZATO, MULTICENTRICO, IN APERTO, DI CONFRONTO DELLA FARMACOCINETICA DI TACROLIMUS IN RICEVENTI PEDIATRICI DI ALLOTRAPIANTO DE NOVO TRATTATI CON UN REGIME IMMUNOSOPPRESSIVO A BASE DI ADVAGRAF O PROGRAF, INCLUSO UN FOLLOW UP A LUNGO TERMINE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Protocol for Phase II Study of Advagraf or Prograf
    Protocollo di studio di Fase II di Advagraf o Prograf
    A.3.2Name or abbreviated title of the trial where available
    PMR-EC-1207
    PMR-EC-1207
    A.4.1Sponsor's protocol code numberPMR-EC-1207
    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 SponsorASTELLAS PHARMA
    B.1.3.4CountryItaly
    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 supportAstellas Pharma Europe Ltd.
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma SpA
    B.5.2Functional name of contact pointDirezione Medica
    B.5.3 Address:
    B.5.3.1Street AddressVia delle Industrie 1
    B.5.3.2Town/ cityCarugate (Milano)
    B.5.3.3Post code20061
    B.5.3.4CountryItaly
    B.5.4Telephone number02 921381
    B.5.5Fax number02 92138217
    B.5.6E-mailCATIA.DICIANNI@IT.ASTELLAS.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 Yes
    D.2.1.1.1Trade name ADVAGRAF*100CPS 0,5MG R.P.
    D.2.1.1.2Name of the Marketing Authorisation holderASTELLAS PHARMA SpA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Prolonged-release capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number.5
    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 Yes
    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 ADVAGRAF*100CPS 1MG R.P.
    D.2.1.1.2Name of the Marketing Authorisation holderASTELLAS PHARMA SpA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Prolonged-release capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    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 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 Yes
    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 Yes
    D.2.1.1.1Trade name ADVAGRAF*100CPS 3MG R.P.
    D.2.1.1.2Name of the Marketing Authorisation holderASTELLAS PHARMA SpA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Prolonged-release capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    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 Yes
    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 Yes
    D.2.1.1.1Trade name ADVAGRAF*50CPS 5MG R.P.
    D.2.1.1.2Name of the Marketing Authorisation holderASTELLAS PHARMA SpA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Prolonged-release capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    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 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 Yes
    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.2.1.1.1Trade name PROGRAF*100CPS 0,5MG
    D.2.1.1.2Name of the Marketing Authorisation holderASTELLAS PHARMA SpA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number.5
    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 Yes
    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: 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.2.1.1.1Trade name PROGRAF*100CPS 1MG
    D.2.1.1.2Name of the Marketing Authorisation holderFUJISAWA Srl
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    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 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 Yes
    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: 7
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name PROGRAF*50CPS 5MG
    D.2.1.1.2Name of the Marketing Authorisation holderASTELLAS PHARMA SpA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 Capsule, hard
    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 INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    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 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 Yes
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Prophylaxis of heart, liver and kidney tranpslant rejection in paediatrics
    profilassi del rigetto d’organo dopo trapianto di cuore, fegato e rene pediatrico
    E.1.1.1Medical condition in easily understood language
    Prevention of heart, liver and kidney transplant in children
    Prevenzione della perdita del cuore, fegato e rene trapiantato nei bambini
    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 14.1
    E.1.2Level LLT
    E.1.2Classification code 10023438
    E.1.2Term Kidney transplant
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10007611
    E.1.2Term Cardiac transplant
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10024716
    E.1.2Term Liver transplantation
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the systemic exposure (AUC0-24h) of tacrolimus for Advagraf versus Prograf after the first dose and following repeated administration in pediatric subjects undergoing de novo allograft transplantation of kidney, liver or heart.
    Confrontare l’esposizione sistemica (AUC0-24h) di tacrolimus per Advagraf con quella per Prograf dopo la somministrazione della prima dose e successivamente a dosi ripetute in soggetti pediatrici sottoposti ad allotrapianto de novo di rene, fegato o cuore.
    E.2.2Secondary objectives of the trial
    To observe the long-term safety and efficacy profile of tacrolimus for Advagraf with that of Prograf in pediatric subjects undergoing de novo allograft transplantation of kidney, liver or heart.
    Confrontare,a lungo termine,il profilo di sicurezza e di efficacia di tacrolimus per Advagraf con quello per Prograf in soggetti pediatrici sottoposti ad allotrapianto de novo di rene,fegato o cuore.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subject is eligible for the study if all of the following apply:
    1. The subject is aged < 16 years of age, undergoing primary liver, kidney or heart allograft transplantation.
    2. The subject must be able to swallow intact Prograf or Advagraf capsules.
    3. Female subjects of child bearing potential must provide a negative urine or serum pregnancy test prior to enrolment in the study.
    4. Male and female subjects that are sexually active must agree to practice effective birth control during the study. (An effective method of birth control is defined as those which result in a low failure rate (ICH M3(R2)) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner).
    5. The subject’s parent(s), or their legal representative(s), has been fully informed and has given written informed consent to participate in the study. The subject has given assent where applicable.
    Additional Inclusion Criteria on Day 1 (Heart transplant subjects):
    6. Subjects, treated since transplantation with Basiliximab or ATG/ Mycophenolate Mofetil (MMF)/steroids, whose gastric motility has resumed and whose renal function is adequate on Day 1.
    Il soggetto sarà arruolabile nello studio nei seguenti casi:
    1. Soggetto di età inferiore a 16 anni, sottoposto a trapianto primario allografico di fegato, rene o cuore.
    2. Soggetto in grado di inghiottire capsule integre di Prograf o Advagraf
    3. I soggetti di sesso femminile potenzialmente fertili devono presentare un test di gravidanza negativo su siero o urine al momento dell’arruolamento.
    4. I soggetti di sesso maschile e femminile che siano sessualmente attivi devono acconsentire a mantenere un metodo altamente efficace di controllo delle nascite durante lo studio (per “metodo altamente efficace di controllo delle nascite” si intende uno di quei metodi che risultano avere un basso tasso di fallimenti (ICH M3(R2)), meno dell’1% all’anno, se usati in maniera costante e corretta come impianti, metodi iniettabili, contraccettivi orali combinati, alcuni dispositivi intrauterini (IUDs), astinenza da rapporti sessuali o il partner vasectomizzato).
    5. Il/I genitore/i del soggetto, o il/i loro rappresentante/i legale/i, è stato completamente informato e ha dato il suo consenso informato scritto a partecipare allo studio. Se applicabile, il soggetto stesso ha dato il proprio assenso.
    Criteri di Inclusione aggiuntivi al Giorno 1 (soggetti sottoposti a trapianto di cuore):
    6. Soggetti, trattati con Basiliximab o ATG/MMF/steroidi sin dal giorno del trapianto, con ripresa della motilità gastrica e adeguata funzionalità renale al Giorno 1.
    E.4Principal exclusion criteria
    Subject will be excluded from participation if any of the following apply at baseline:
    1. Subject is receiving a multi-organ transplant or has previously received an organ transplant (including re-transplantation).
    2. Subject with pulmonary vascular resistance 4 Wood units despite medication.
    3. Subject with significant renal impairment, defined as having serum creatinine ≥230 μmol/l (≥2.6 mg/dl) pre-transplantation. (Not applicable for renal transplanted subjects)
    4. Subject with significant liver disease, defined as having continuously elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels of ≥3 times the upper value of the normal range of the investigational site during the past 28 days. (Not applicable for liver transplanted subjects)
    5. Subject with malignancies or a history of malignancy within the last 5 years, with the exception of those with basalioma or squamous cell carcinoma of the skin that has been treated successfully. (Not applicable for transplanted subjects with a primary organ diagnosis of cancer)
    6. Subject with significant, uncontrolled concomitant infections and/or severe diarrhoea, vomiting, active upper gastrointestinal disorder that may affect the absorption of tacrolimus or active peptic ulcer.
    7. Subject requiring systemic immunosuppressive medication for any other indication than transplantation.
    8. Subject or donor known to be HIV or HCV or HBV positive.
    9. Subject is allergic or intolerant to steroids, macrolide antibiotics, MMF or tacrolimus.
    10. Subject is pregnant or breast-feeding.
    11. Subject is unlikely to comply with the visits scheduled in the protocol.
    12. Subject has any form of substance abuse, psychiatric disorder or condition which, in the opinion of the Investigator, may complicate communication with the Investigator.
    13. Subject is participating or has participated in another clinical trial and/or those taking or having taken an investigational/non-registered drug in the past 28 days.
    14. Subject is taking or requiring to be treated with medication or substances known to interfere with tacrolimus metabolism and listed in section below ‘Prohibited Concomitant Medication’ or having taken such medication within 28 days prior to inclusion.
    Il soggetto verrà escluso dalla partecipazione allo studio nei seguenti casi:
    1. Il soggetti sta per ricevere un trapianto multi-organo o ha precedentemente ricevuto un trapianto d’organo (incluso un ritrapianto).
    2. Soggetto con resistenza vascolare polmonare &gt;4 unità Wood nonostante terapia.
    3. Soggetto con compromessa funzionalità renale significativa, definita come creatinina sierica &gt; 230 μmol/l (&gt; 2.6 ml/dl) pre-trapianto (eccetto i soggetti sottoposti a trapianto di rene).
    4. Soggetto con epatopatia significativa, definita come livelli di SGPT/ALT e/o SGOT/AST continuativamente elevati e/o livelli di bilirubina totale ≥ 3 volte il limite superiore della norma del centro sperimentale negli ultimi 28 giorni (eccetto i soggetti sottoposti a trapianto di fegato).
    5. Soggetto con neoplasia maligna o storia clinica di neoplasia maligna entro gli ultimi 5 anni, ad eccezione del carcinoma basocellulare o a cellule squamose della pelle trattato con successo (eccetto i soggetti sottoposti a trapianto con diagnosi primaria di tumore).
    6. Soggetto con infezioni concomitanti significative e non controllate e/o grave diarrea, vomito, disordini attivi del tratto gastrointestinale superiore tali da avere effetto sull’assorbimento di tacrolimus o ulcera peptica attiva.
    7. Soggetto che richieda la somministrazione di un immunosoppressore sistemico per qualsiasi indicazione diversa dal trapianto.
    8. Soggetto o donatore notoriamente HIV o HCV o HBV positivo.
    9. Soggetto allergico o intollerante a steroidi, antibiotici macrolidi, MMF o tacrolimus.
    10. Soggetto in stato di gravidanza o allattamento.
    11. Soggetto verosimilmente poco in grado di aderire allo schema delle visite previsto dal protocollo.
    12. Soggetto con qualunque forma di abuso di sostanze, disturbo psichiatrico o condizione che, a giudizio dello sperimentatore, possa complicare la comunicazione con lo sperimentatore.
    13. Soggetto che stia attualmente partecipando o abbia partecipato ad un’altra sperimentazione clinica e/o stia assumendo o abbia assunto un farmaco sperimentale negli ultimi 28 giorni.
    14. Soggetto che stia assumendo o che necessiti di essere trattato con farmaci o sostanze note per interferire con il metabolismo di tacrolimus ed elencate nella sezione “Farmaci Concomitanti Proibiti” o che abbia assunto tali farmaci nei 28 giorni precedenti alla data di inclusione.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Pharmacokinetic Variables
    • The systemic exposure (AUC0-24h at each of Day 1, Day 7 and Day 28) of tacrolimus after first dose and under steady state conditions.

    Primary Safety Variables
    • AEs
    • Laboratory parameters
    • Vital signs
    Variabile Primaria di Farmacocinetica
     L’esposizione sistemica (AUC0-24h al Giorno 1, Giorno 7 e Giorno 28) di tacrolimus dopo la prima dose e in condizioni di steady state

    Variabili Primarie di Sicurezza
     Incidenza di Eventi Avversi (AE)
     Parametri di Laboratorio
     Segni vitali
    E.5.1.1Timepoint(s) of evaluation of this end point
    AUC0-24h at each of Day 1, Day 7 and Day 28
    Long term safety at 2, 3, 6, and 12 months
    AUC0-24h al Giorno 1, Giorno 7 e Giorno 28
    Sicurezza a lungo termine a 2, 3, 6 e 12 mesi
    E.5.2Secondary end point(s)
    Secondary Pharmacokinetic Variables
    The following PK parameters for tacrolimus will be determined for each profile
    • Cmax
    • tmax
    • C24

    Efficacy Variables
    • Rejection episodes
    • Subject and graft survival
    Variabili Secondarie di Farmacocinetica
    Saranno determinati per tacrolimus i seguenti parametri di PK per ciascun profilo
     Cmax
     tmax
     C24

    Variabili di Efficacia
     Episodi di Rigetto
     Sopravvivenza dell’organo e del paziente
    E.5.2.1Timepoint(s) of evaluation of this end point
    PK variables at Day 1, Day 7 and Day 28

    Long term efficacy variables at 2, 3, 6 and 12 months
    Variabili di farmacocinetica al Giorno 1, Giorno 7 e Giorno 28

    Variabili di efficacia a lungo termine a 2, 3, 6 e 12 mesi
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    The study will not be discontinued early based on the results of PK data. Part B, including baseline characteristics, safety and efficacy data from Part A, will be reported once the one year follow up has been completed
    Lo studio non sarà interrotto anticipatamente sulla base dei risultati dei dati di farmacocinetica.Il report relativo alla Parte B sarà fornito al completamento del periodo di follow-up di un anno.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months24
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months24
    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 Yes
    F.1.1Number of subjects for this age range: 64
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 32
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 32
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 64
    F.4.2.2In the whole clinical trial 64
    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)
    No plan to continue treatment as treatment options for this condition are available
    Non si prevede di continuare il trattamento essendo per questa condizione disponibili opzioni terapeutiche
    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 Decision2012-04-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-04-13
    P. End of Trial
    P.End of Trial StatusOngoing
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