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    The EU Clinical Trials Register currently displays   41228   clinical trials with a EudraCT protocol, of which   6756   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2021-000726-10
    Sponsor's Protocol Code Number:ADAPT
    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:2021-06-08
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2021-000726-10
    A.3Full title of the trial
    Evaluating the short-term renal and systemic effects of Dapagliflozin in non-diabetic patients with stage IV CKD at risk of ESKD because of severe renal insufficiency and persistent proteinuria: A prospective, randomized, double-blind, placebo-controlled, cross-over study
    Valutazione degli effetti renali e sistemici a breve termine di Dapagliflozin, in pazienti non diabetici con CKD allo stadio IV a rischio di ESKD per grave insufficienza renale e proteinuria persistente: uno studio prospettico, randomizzato, in doppio cieco, controllato con placebo, con disegno cross-over
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluating the short-term renal and systemic effects of Dapagliflozin in non-diabetic patients with stage IV CKD at risk of ESKD because of severe renal insufficiency and persistent proteinuria: A prospective, randomized, double-blind, placebo-controlled, cross-over study
    Valutazione degli effetti renali e sistemici a breve termine di Dapagliflozin, in pazienti non diabetici con CKD allo stadio IV a rischio di ESKD per grave insufficienza renale e proteinuria persistente: uno studio prospettico, randomizzato, in doppio cieco, controllato con placebo, con disegno cross-over
    A.3.2Name or abbreviated title of the trial where available
    Dapagliflozin in non-diabetic stage IV CKD
    Dapagliflozin in pazienti non diabetici con insufficienza renale cronica al IV stadio
    A.4.1Sponsor's protocol code numberADAPT
    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 SponsorIRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
    B.1.3.4CountryItaly
    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 supportAstraZeneca
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIstituto di Ricerche Farmacologiche Mario Negri IRCCS
    B.5.2Functional name of contact pointLab. Attività Regolatorie Studi Cli
    B.5.3 Address:
    B.5.3.1Street AddressVia G.B. Camozzi, 3
    B.5.3.2Town/ cityRanica - BG
    B.5.3.3Post code24020
    B.5.3.4CountryItaly
    B.5.4Telephone number0354535307
    B.5.5Fax number0354535371
    B.5.6E-mailpaola.boccardo@marionegri.it
    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 FORXIGA - 10 MG - COMPRESSE RIVESTITE CON FILM- USO ORALE - BLISTER CALENDARIZZATO (ALU/ALU) - 28 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderASTRAZENECA AB
    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.3.1Product namedapagliflozin
    D.3.2Product code [dapagliflozin]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdapagliflozin
    D.3.9.1CAS number 461432-26-8
    D.3.9.2Current sponsor codeBMS-512148-05
    D.3.9.3Other descriptive namedapagliflozin propanediol
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-diabetic stage IV Chronic Kidney Disease (CKD)
    Insufficienza renale cronica non diabetica IV stadio
    E.1.1.1Medical condition in easily understood language
    Non-diabetic stage IV Chronic Kidney Disease (CKD)
    Insufficienza renale cronica non diabetica IV stadio
    E.1.1.2Therapeutic area Diseases [C] - Male diseases of the urinary and reproductive systems [C12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10009119
    E.1.2Term Chronic renal failure
    E.1.2System Organ Class 100000004857
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess whether:
    1. Six-week treatment with 10 mg dapagliflozin daily as compared to six-week treatment with placebo may induce a significant reduction in measured GFR (taken as a marker of amelioration of glomerular hyperfiltration)
    2. Amelioration of glomerular hyperfiltration translates into a significant reduction in 24-hour urinary protein excretion (taken as a marker of amelioration of glomerular sieving function).
    Valutare se:
    1 Un trattamento di sei settimane con 10 mg di dapagliflozin al giorno può indurre una riduzione significativa del GFR misurato (considerato come un marker di miglioramento dell'iperfiltrazione glomerulare) rispetto ad un trattamento di sei settimane con placebo;
    2 Il miglioramento dell'iperfiltrazione glomerulare si traduce in una significativa riduzione dell'escrezione urinaria di proteine nelle 24 ore (considerata come un marcatore di miglioramento della funzione di “setaccio” del glomerulo).
    E.2.2Secondary objectives of the trial
    To assess treatment effect on renal perfusion, markers of glomerular hemodynamics and tubular function, and clinical and metabolic/ laboratory parameters in the study group as a whole and in patients with or without pre-diabetes (2-hour plasma glucose during 75-gram oral glucose tolerance test (OGTT) > or < 140 mg/dl) considered separately.
    Valutare l'effetto del trattamento sulla perfusione renale, sui marcatori dell'emodinamica glomerulare e della funzione tubulare e sui parametri clinici e metabolici/di laboratorio, sia nel gruppo di studio nel suo complesso che nei pazienti in presenza o in assenza di condizione pre-diabetica, (valori di glucosio plasmatico 2 ore dopo test da carico orale con 75 grammi di glucosio > o <140 mg/dl, rispettivamente) considerati separatamente.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1 Provision of informed consent prior to any study specific procedures
    2 Male or female more than 18 year old
    3 Non-diabetic Stage-IV CKD
    4 Fasting blood glucose = 125 mg (= 6.9 mmol/l) and HbA1C =6.4% (= 47 mmol/mol)58 without treatment with oral blood glucose lowering medications and/or insulin
    5 Two-hour plasma glucose <200 mg/dl during 75-g oral glucose tolerance test (OGTT)58
    6 Persistent proteinuria (24-hour urinary protein excretion = 0.5 grams in at least two consecutive evaluations >1 week apart) despite RAS inhibitor therapy with ACE inhibitors and/or ARBs (or without RAS inhibitors in patients with specific contraindications to these medications)
    7 eGFR 15 to 30 ml/min/1.73 m2 by CKD-Epi equation
    8 Blood pressure <150/90 mmHg without changes in blood pressure lowering medications over the last four weeks before the randomization
    9 Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
    10 Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of dapagliflozin\placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
    11 Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of IMP to prevent pregnancy in a partner.
    12 Subjects who are blood donors should not donate blood during the study and for 3 months following their last dose of dapagliflozin\placebo.
    1. Consenso informato prima di qualsiasi procedura specifica dello studio
    2. Maschi e femmine di età superiore a 18 anni
    3. CKD non-diabetica allo stadio IV
    4. Glicemia a digiuno = 125 mg (= 6.9 mmol/l) e HbA1C =6.4% (= 47 mmol/mol), in assenza di trattamento con farmaci ipoglicemizzanti orali e/o insulina
    5. Glicemia <200 mg/dl 2 ore dopo test da carico orale (OGTT) con 75-g di glucosio
    6. Proteinuria persistente (escrezione urinaria di proteine nelle 24 ore = 0.5 grammi in almeno due misurazioni consecutive a distanza di 1 settimana), nonostante terapia anti-RAS con ACE inibitori e/o ARBs (oppure con farmaci non inibitori RAS in pazienti con specifiche controindicazioni a questi farmaci)
    7. eGFR compreso tra 15 e 30 ml/min/1.73m2, calcolato con l’equazione CKD-Epi
    8. Pressione sanguigna <150/90 mmHg, e nessuna modifica alla terapia antipertensiva nelle 4 settimane antecedenti la randomizzazione
    9. Test di gravidanza negativo (urine o siero) per soggetti di sesso femminile in età fertile
    10. I soggetti di sesso femminile devono essere in post-menopausa da 1 anno, chirurgicamente sterili o devono utilizzare un metodo contraccettivo accettabile (definito come una combinazione di un metodo di barriera con uno spermicida) per tutta la durata dello studio (da quando viene firmato il consenso) e per i 3 mesi successivi all'ultima somministrazione di dapagliflozin/placebo per prevenire la gravidanza. Inoltre, sono consentiti contraccettivi orali, impianti contraccettivi approvati, contraccezione iniettabile a lungo termine, dispositivi intrauterini o legatura delle tube. La contraccezione orale da sola non è accettabile; devono essere utilizzati metodi di barriera aggiuntivi in combinazione con uno spermicida.
    11. I soggetti di sesso maschile devono essere chirurgicamente sterili o utilizzare un metodo contraccettivo accettabile (definito come una combinazione di metodi di barriera con spermicidi) per tutta la durata dello studio (da quando viene firmato il consenso) e per i 3 mesi successivi all'ultima somministrazione di IMP per prevenire la gravidanza nel partner.
    12. I soggetti donatori di sangue devono evitare di donare il sangue per tutta la durata dello studio e per i 3 mesi successivi all‘ultima somministrazione di dapagliflozin/placebo.
    E.4Principal exclusion criteria
    1 Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
    2 Participation in another clinical study with an investigational product during the last month
    3 Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2-inhibitor associated reduction in sodium pool and kidney perfusion pressure)
    4 Rapidly progressive kidney disease (e GFR reduction = 30% over the last three months) and expected risk of progression to end stage kidney failure and need of renal replacement therapy by dialysis or transplantation during the study period.
    5 Active systemic autoimmune diseases;
    6 Concomitant treatment with steroids or any other immunosuppressive agent
    7 Hypersensitivity to the active principle (dapagliflozin) or any of the excipients (e.g. lactose);
    8 Severe/unstable heart failure with or without decreased systolic function requiring hospitalization or changes in pharmacological therapy over the last three months
    9 Uncontrolled hypertension (BP >150/90 mmHg despite optimized pharmacological treatment and diet or symptomatic hypotension
    10 Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening
    11 Known to have tested positive for human immunodeficiency virus
    12 Drug or alcohol abuse
    13 Inability to fully understand the possible risks and benefits related to study participation
    14 If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period;
    15 If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
    16 Participation in another interventional clinical trial within the 4 weeks prior to screening.
    1. Coinvolgimento nella pianificazione e/o conduzione dello studio;
    2. Partecipazione ad un altro studio farmacologico nel mese precedente;
    3. Malattia renale ischemica (dovuta al possibile aumento del rischio di insufficienza renale acuta in seguito alla riduzione del pool di sodio e della pressione di perfusione renale associate alla somministrazione di un'inibitore SGLT2)
    4. Malattia renale rapidamente progressiva (riduzione del eGFR = 30% negli ultimi 3 mesi) e rischio atteso di progressione verso l'insufficienza renale allo stadio terminale e necessità di terapia renale sostitutiva mediante dialisi o trapianto durante il periodo dello studio.
    5. Malattie autoimmuni sistemiche attive
    6. Terapia concomitante con steroidi o altri farmaci immunosoppressivi
    7. Ipersensibilità al principio attivo (dapagliflozin) o ad uno qualsiasi degli eccipienti (come il lattosio);
    8. Insufficienza cardiaca severa/instabile, con o senza riduzione della funzione sistolica, che ha richiesto ospedalizzazione o eventuali modifiche alla terapia farmacologica negli ultimi 3 mesi;
    9. Ipertensione incontrollata (BP >150/90 mmHg), nonostante terapia farmacologica/dieta ottimizzate o ipotensione sintomatica;
    10. Positività allo screening verso l’anticorpo dell’epatite C, l’antigene di superficie dell’epatite B, o l’anticorpo core dell’epatite B;
    11. Positività al virus dell'HIV;
    12. Abuso di droga o alcol
    13. Incapacità a comprendere pienamente i possibili rischi e benefici legati alla partecipazione allo studio;
    14. Paziente di sesso femminile: gravidanza o allattamento, ovvero intenzione di avere un figlio o di donare gli ovuli prima, durante, o nei 90 giorni successivi all’ultima somministrazione del farmaco;
    15. Paziente di sesso maschile:, il soggetto intende donare lo sperma nel corso dello studio o nei 90 giorni successivi all’ultima somministrazione del farmaco;
    16. Partecipazione ad un altro studio clinico sperimentale nelle 4 settimane antecedenti lo screening.
    E.5 End points
    E.5.1Primary end point(s)
    1. GFR measured by the Iohexol plasma clearance technique59
    2. 24-hour urinary protein excretion (median of three measurements in three consecutive 24-hour urine collections at start and at the end of each Treatment Period with dapagliflozin or placebo)
    1 GFR misurato con la tecnica di clearance plasmatica dello ioexolo
    2 Escrezione urinaria di proteine nelle 24 ore (mediana di tre misurazioni in tre raccolte consecutive di urine nelle 24 ore all'inizio e alla fine di ciascun periodo di trattamento con dapagliflozin o placebo)
    E.5.1.1Timepoint(s) of evaluation of this end point
    In each visit of the study.
    In ogni visita dello studio.
    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 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) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group 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) No
    E.8.2.2Placebo Yes
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    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 Information not present in EudraCT
    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
    LVLS
    LVLS
    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 months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 16
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 16
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 32
    F.4.2.2In the whole clinical trial 32
    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)
    After a subject has ended his/her participation in the trial he/she will be treated with the best therapy available.
    Al termine della loro partecipazione allo studio i pazienti saranno trattati con la migliore terapia disponibile.
    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 Decision2021-06-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-04-16
    P. End of Trial
    P.End of Trial StatusOngoing
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