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   43873   clinical trials with a EudraCT protocol, of which   7293   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:2020-001655-41
    Sponsor's Protocol Code Number:35RC19_8877_DIPLOID
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2020-07-20
    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 ConcernedFrance - ANSM
    A.2EudraCT number2020-001655-41
    A.3Full title of the trial
    P-glypoprotein inhibition effect on the pharmacokinetics of two tacrolimus formulations: prolonged and extended-release
    Effet De l’inhibition de la glycoprotéine P sur la pharmacocinétique de deux formes galéniques de tacrolimus
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    P-glypoprotein inhibition effect on the pharmacokinetics of two tacrolimus formulations: prolonged and extended-release
    Effet De l’inhibition de la glycoprotéine P sur la pharmacocinétique de deux formes galéniques de tacrolimus
    A.3.2Name or abbreviated title of the trial where available
    DIPLOID
    DIPLOID
    A.4.1Sponsor's protocol code number35RC19_8877_DIPLOID
    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 SponsorCHU de Rennes
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCHU de Rennes
    B.4.2CountryFrance
    B.4.1Name of organisation providing supportChiesi
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCHU de Rennes
    B.5.2Functional name of contact pointLE NAOU
    B.5.3 Address:
    B.5.3.1Street Address2 rue Henri Le Guilloux
    B.5.3.2Town/ cityRennes
    B.5.3.3Post code35033
    B.5.3.4CountryFrance
    B.5.4Telephone number33299282555
    B.5.5Fax number33299283999
    B.5.6E-maildri@chu-rennes.fr
    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
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAdvagraf
    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.3.11 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 Envarsus
    D.2.1.1.2Name of the Marketing Authorisation holderChiesi Farmaceutici S.p.A.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEnvarsus
    D.3.4Pharmaceutical form Prolonged-release tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    healthy volunteers
    Volontaires sains
    E.1.1.1Medical condition in easily understood language
    healthy volunteers
    volontaires sains
    E.1.1.2Therapeutic area Not possible to specify
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the P-gp inhibition on tacrolimus exposure in healthy volunteers administered Advagraf® or Envarsus®.
    Evaluer l’effet de l’inhibition de la P-gp sur la cinétique du tacrolimus après administration unique chez le volontaire sain pour une forme à libération prolongée (Advagraf®) et une forme à libération très prolongée LCP-tacro (Envarsus®).
    E.2.2Secondary objectives of the trial
    To evaluate the P-gp inhibition on intracellular tacrolimus pharmacokinetics in healthy volunteers administered Advagraf® or Envarsus®.
    To evaluate the intracellular diffusion between Advagraf® or Envarsus®.
    To evaluate the impact of ABCB1 genotypes on blood and intracellular exposure of tacrolimus.
    To evaluate the impact of other genotypes (coding for metabolism or drug transport) of interest on blood and intracellular exposure of tacrolimus.
    -Evaluer l’effet de l’inhibition de la P-gp sur la pharmacocinétique intracellulaire des deux formes galéniques de tacrolimus, avec et sans inhibition de la P-gp. La P-gp est présente à la surface du lymphocyte et peut donc être inhibée par le vérapamil. Le dosage du tacrolimus dans les cellules mononuclées sanguines périphériques (PBMC) pourrait donc se révéler un indicateur plus fin de son effet puisque le lymphocyte est le site d’action du médicament [20].
    - Evaluer si la diffusion intracellulaire du médicament est différente entre les formes galéniques.
    - Evaluer l’impact du génotype ABCB1 sur la pharmacocinétique sanguine et intracellulaire du tacrolimus.
    - Evaluer l’impact d’autres génotypes d’intérêt (codant pour des enzymes du métabolisme ou de transport du tacrolimus).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - adults (> 18 years)
    - Non smokers
    - Biological parameters within normal range (blood count, urea, creatinine, AST, ALT, GGT, bilirubine)
    - BMI within 18 and 25
    - Negative urinary and plasma pregnancy test
    - Informed consent
    - adulte (18 ans ou plus) ;
    - non-fumeur (depuis au moins 6 mois) ;
    - valeurs des examens biologiques de routine (NFS-plaquettes, ionogramme sanguin, urée, créatinine et glucose plasmatiques, hémostase (TP), bilan hépatique (ASAT, ALAT, GGT, bilirubine)) comprises dans les normales des laboratoires ;
    - IMC compris entre 18 et 25 ;
    - test de grossesse plasmatique négatif pour les femmes ;
    - ayant donné un consentement libre et éclairé par écrit.
    E.4Principal exclusion criteria
    - participation to another study with incompatible procedure regarding the French law on research
    - Treatment with a drug drug interaction with tacrolimus
    - Cardiac rhythm at rest below 50 bpm
    - Cardiac issue detected on electrocardiogram
    - Cancer or history of cancer
    - Chronic infection or history of chronic infection
    - Diabetes or history of diabetes
    - Hypertension or history of hypertension
    - Pregnancy or lactation
    - Deprived of liberty (curatorship, guardianship or incarcerate)
    - participation à un autre protocole de type RIPH ;
    - prise d’un traitement susceptible d’interagir avec la pharmacocinétique du tacrolimus (Antibiotiques macrolides et apparentés (clarithromycine, erythromycine, spiramycine, roxithromycine, josamycine, clindamycine), cotrimoxazole, antifongiques azolés (itraconazole, miconazole, kétoconazole, voriconazole, posaconazole, fluconazole, isavuconazole), rifampicine, rifabutine, amiodarone, inhibiteurs calciques (amlodipine, nicardipine, felodipine, isradipine, lercanidipine, nifedipine, diltiazem, verapamil), Antirétroviraux (efavirenz, nevirapine, etravirine, ritonavir, darunavir, atazanavir, lopinavir), Inhibiteurs de la pompes à protons (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole), antiacides (cimetidine, ranitidine, famotidine, hydroxyde d’aluminium, phosphate d’aluminium, hydroxyde de magnésium, alginate), antiépileptiques (carbamazépine, acide valproique, phénobarbital, phénytoïne).
    - anomalie cliniquement significative à l’électrocardiogramme (ECG) ;
    - cancer ou antécédent de cancer
    - infection chronique ou antécédent d’infection chronique
    - insuffisance rénale ou antécédent d’insuffisance rénale
    - diabète ou antécédent de diabète
    - hypertension artérielle ou antécédent d’hypertension artérielle
    - femme enceinte ou allaitante ;
    - incapable majeur (sauvegarde de justice, curatelle et tutelle), personne privée de liberté.
    E.5 End points
    E.5.1Primary end point(s)
    Change in area under the curve of tacrolimus blood concentrations between 0 and 24h.
    Modification de l’aire sous la courbe (ASC) des concentrations sanguines mesurées en fonction du temps (0-24h) lors de la réalisation d’une pharmacocinétique complète.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Between 0 and 24 hour.
    Entre 0 et 24 heure
    E.5.2Secondary end point(s)
    - Blood pharmacokinetic parameters (peak concentration (Cmax), trough concentration (Cmin), Apparent clearance (Cl/F) and half-life (T1/2)).
    - Intracellular pharmacokinetic parameters (AUC, Cmax, Cmin, Cl/F, T1/2).
    - ABCB1 genotypes
    - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…).
    - Autres paramètres pharmacocinétiques sanguins du tacrolimus (Concentration maximale (Cmax), Concentration résiduelle (Cmin), Clairance apparente (Cl/F) et demi-vie (T1/2)).
    - Paramètres pharmacocinétiques intracellulaires des deux formes galéniques (ASC, Cmax, Cmin, Cl/F, T1/2).
    - Génotype ABCB1.
    - Génotypes d’intérêt codant pour des enzymes du métabolisme (CYP3A4, CYP3A5…) ou du transport des médicaments (CNT3…).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Blood pharmacokinetic parameters:
    Cmax Envarsus: 6-8 hour
    Cmax Advagraf: 2-3 hour
    Cmin: H24
    Clearance: 0-24 hour
    Half-life: 0-24 hour

    Intracellular pharmacokinetic parameters:
    AUC: between 0 and 24 hour
    Cmax Envarsus: 6-8 hour
    Cmax Advagraf: 2-3 hour
    Cmin: H24
    Clearance: 0-24 hour
    Half-life: 0-24 hour
    - ABCB1 génotypes: D0
    - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…): D0
    Autres paramètres pharmacocinétiques sanguins du tacrolimus:
    Cmax Envarsus: 6-8 hour
    Cmax Advagraf: 2-3 hour
    Cmin: H24
    Clearance: 0-24 hour
    Half-life: 0-24 hour

    Paramètres pharmacocinétiques intracellulaires des deux formes galéniques:
    AUC: entre 0 and 24 heure
    Cmax Envarsus: 6-8 heure
    Cmax Advagraf: 2-3 heure
    Cmin: H24
    Clearance: 0-24 heure
    Half-life: 0-24 heure
    - ABCB1 génotypes: J0
    - Other genotypes of interest coding for metabolism (CYP3A4, CYP3A5…) or drug transport (CNT3…): J0
    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 No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind Yes
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    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 Yes
    E.8.2.3.1Comparator description
    Médicament auxiliaire (Vérapamil)
    Challenge agent (Vérapamil)
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study corresponds to the last visit of the last person who is a subject in the study.
    La date de fin de la recherche correspond à la date de la dernière visite du dernier volontaire se prêtant à la recherche.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    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: 28
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 28
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-07-20. Yes
    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 state28
    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 - study with healthy volunteers
    Aucun - étude sur volontaires sains
    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 Decision2020-08-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-15
    P. End of Trial
    P.End of Trial StatusCompleted
    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-Wed May 08 05:00:59 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA