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    Summary
    EudraCT Number:2013-005031-24
    Sponsor's Protocol Code Number:1289.5
    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:2014-11-19
    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 number2013-005031-24
    A.3Full title of the trial
    A multi-centre, double-blind, parallel-group, randomised controlled study to investigate efficacy, safety and tolerability of orally administered BI 409306 during a 12-week treatment period compared to placebo in patients with Alzheimer Disease (AD)
    Studio multicentrico, in doppio cieco a gruppi paralleli, randomizzato e controllato con placebo per valutare l’efficacia, la sicurezza e la tollerabilità del BI 409306 per somministrazione orale per un periodo di 12 settimane di trattamento in confronto a placebo, in pazienti con malattia di Alzheimer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Alzheimer Disease Proof of Concept Study with BI 409306 versus Placebo
    Studio “proof of concept” sulla malattia di Alzheimer con BI 409306 versus Placebo
    A.4.1Sponsor's protocol code number1289.5
    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 SponsorBoehringer Ingelheim Italia S.p.A.
    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 supportBoehringer Ingelheim Italia S.p.A.
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBoehringer Ingelheim Pharma GmbH & Co. KG
    B.5.2Functional name of contact pointQRPE PSC CT Information Disclosure
    B.5.3 Address:
    B.5.3.1Street AddressBinger Strasse 173
    B.5.3.2Town/ cityIngelheim am Rhein
    B.5.3.3Post code55216
    B.5.3.4CountryGermany
    B.5.4Telephone number001 800 243 0127
    B.5.5Fax number001 800 821 7119
    B.5.6E-mailclintriage.rdg@boehringer-ingelheim.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBI 409306
    D.3.2Product code BI 409306
    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 INNn.a.
    D.3.9.2Current sponsor codeBI 409306
    D.3.9.3Other descriptive nameBI 409306
    D.3.9.4EV Substance CodeSUB166499
    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: 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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBI 409306
    D.3.2Product code BI 409306
    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 INNn.a.
    D.3.9.2Current sponsor codeBI 409306
    D.3.9.3Other descriptive nameBI 409306
    D.3.9.4EV Substance CodeSUB166499
    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.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBI 409306
    D.3.2Product code BI 409306
    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 INNn.a.
    D.3.9.2Current sponsor codeBI 409306
    D.3.9.3Other descriptive nameBI 409306
    D.3.9.4EV Substance CodeSUB166499
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    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
    Patients with diagnosis of AD according to the following criteria:
    • Symptoms noticed by the patients and/or informant
    • Cognitive testing confirming symptoms
    • Biomarker evidence of AD pathology
    • No evidence of other forms of dementia
    • No other concomitant illness or medication which could confound or prohibit completion in the trial by the patient
    I pazienti con diagnosi di malattia di Alzheimer secondo i seguenti criteri:
    • Sintomi riscontrati dai pazienti e/o da persona informata
    • test cognitivi che confermino i sintomi
    • Evidenza di Biomarker della patologia
    • Nessuna evidenza di altre forme di demenza
    • Nessun altra malattia concomitante o farmaci che potrebbero confondere o compromettere il completamento dello studio da parte del paziente
    E.1.1.1Medical condition in easily understood language
    Patients who suffer by mental disorders which are caused by symptoms of the Alzheimer's Disease
    I pazienti che soffrono per disturbi mentali che siano causati da sintomi della malattia di Alzheimer
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10001896
    E.1.2Term Alzheimer's disease
    E.1.2System Organ Class 100000004852
    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 efficacy of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD)
    Valutare l'efficacia di diverse dosi di BI 409306 rispetto al placebo nel trattamento della malattia di Alzheimer
    E.2.2Secondary objectives of the trial
    To assess safety and tolerability of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD)
    Valutare il profolo di sicurezza e tollerabilità di diverse dosi di BI 409306 rispetto al placebo nel trattamento della malattia di Alzheimer
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Male and female patients with an age of at least 55 years
    - Body weight not lower than 50 kgs
    - Patients with early signs of Alzheimer Disease
    - Treatment naive patients or patients who have not received
    prescribed drugs for treatment of AD (including acetyl cholinesterase
    inhibitors (donepezil, galantamine, rivastigmine, tacrine, phenserine)
    and Memantine
    - Patients must have at least 6 years of formal education and fluency in
    the test language as verbally confirmed by the patient and documented
    by the study investigator.
    - Patients must have given written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to any study procedures. All patients must be able to give informed consent personally and have capacity for such consent. An informed consent given by a legal representative will not be accepted.
    - Patients must have a reliable study partner (per investigator
    judgement, for instance a family member, guardian, partner etc.)
    1. Paziente uomo o donna, di età ≥ 55 anni. Possono essere inclusi pazienti oltre gli 85 anni se hanno un accettabilmente buono stato di salute generale (ed es. considerando le patologie concomitanti, la capacità fisica di effettuare le procedure richieste dallo studio (visite etc) secondo giudizio dello sperimentatore.
    2. Peso ≥ 50 kgs.
    3. Paziente con diagnosi confermata di malattia di Alzheimer (AD) in stadio prodromico definita dai seguenti punteggi nei test neuropsicologici:
    - Mini-Mental State Examination (MMSE) - risultato: ≥ 24
    e
    - score globale della Clinical Dementia Rating (CDR) scale di 0 oppure 0,5
    e
    - Free and Cued Selective Recall Reminding Test (FCSRT) - risultato:
    o free recall test: ≤ 20 (su 48) e
    o total recall test: ≤ 42 (su 48)
    I pazienti che non ottengono il risultato necessario sull’FCSRT faranno anche il test Wechsler Memory Visual Paired Associates. Se questo esame mostra un deficit cognitivo più ampio (peggiore di) 1 deviazione standard rispetto alla media (confronto ai valori di riferimento per età e grado di educazione per l’inclusione), il paziente può essere considerate includibile nello studio.
    4. Confermata presenza di markers di patologia AD secondo i seguenti punti a) o b):*
    a) Presenza nel liquido cefalorachidiano (CSF) di (campioni risalenti a massimo 4 mesi prima possono essere ammessi, vedi sez del protocollo 5.6.1 ed appendice 10.2 per tutti i dettagli):
    - basse concentrazioni di Aβ1-42 (< 640 pg/mL) ed aumentate concentrazioni di tau totale (>375 pg/ml);
    e/o
    - basse concentrazioni di Aβ1-42 (< 640 pg/mL) ed aumentate concentrazioni di fosfo-tau (> 52 pg/mL nel liquido cefalorachidiano);
    oppure:
    b) Deposizione anomala di amiloide da scansione PET cerebrale. Eventuali scansioni PET già disponibili verranno ritenute valide ai fini della sperimentazione (se in accordo agli standard di qualità descritti dal protocollo, Sez 5.3.2.1)
    * Nota – si potranno effettuare la CSF o la PET, quale che sia la procedura standard del centro sperimentale e/o approvata dal Comitato Etico.
    5. Paziente naïf al trattamento (che non ha assunto farmaci prescritti per il trattamento della AD (inclusi inibitori dell’acetil-colinesterasi -donepezil, galantamina, rivastigmina, tacrina, fenserina- e memantina).
    6. Paziente con almeno 6 anni di scolarizzazione formale e fluente nella lingua dei test, come confermato verbalmente dal paziente e documentato dallo sperimentatore.
    7. Paziente che ha fornito il proprio consenso informato scritto in accordo alle line guida GCP e legislazione locale prima di qualunque procedure dello studio. I pazienti devono essere in grado di fornire autonomamente il proprio consenso informato: pertanto, soggetti che necessitino di rappresentante legale non saranno inclusi nello studio.
    8. Paziente con uno “study partner” (o “assistente per lo studio”) affidabile secondo il giudizio dello sperimentatore. Questa persona deve essere in stretto contatto con il paziente e acconsentire ad accompagnarlo/a a tutte le visite dello studio in cui è richiesto. Deve inoltre acconsentire ad essere contattabile telefonicamente e deve contribuire all’effettuazione dei test neuropsicologici del paziente laddove richiesto. Questa persona deve essere in grado di comunicare nella lingua in cui il paziente effettua i test e deve costituire contatto di “back-up” per lo staff del centro. Questa persona deve firmare un consenso informato separato dove è descritto il suo ruolo nell’ambito dello studio.
    E.4Principal exclusion criteria
    -Cognitive impairment with any etiology other than AD (based on
    clinical data and/or current laboratory findings and/or a pre-existing MRI or CT of the brain which is not older than 12 months prior to screening visit) for example: neurosyphilis, craniocerebral trauma, small vessel disease
    -Substantial concomitant cerebrovascular disease (defined by a history of a stroke / intracranial haemorrhagia) temporally related to the onset of worsening of cognitive impairment per investigator judgement
    -Medical history of cancer (except for basal cell carcinoma) and/or
    treatment for cancer within the last 5 years
    -Medical history or diagnosis of any of symptomatic and
    unstable/uncontrolled conditions per investigator judgement
    -Severe renal impairment defined with a glomerular filtration rate
    (GFR) < 30ml/min/1.73m2 in the screening central lab report
    -Any other psychiatric disorders such as schizophrenia, or mental
    retardation
    -Any suicidal actions in the past 2 years (per investigator judgement
    i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
    -Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity
    Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
    -Previous participation in investigational drug studies of cognitive
    impairment. Currently ongoing treatment with non-prescription
    medications, vitamins or other nutritional formulations is allowed
    however these should be captured in the electronic case report form (e-CRF)
    -Significant history of drug dependence or abuse (including alcohol, as defined in Diagnostic and Statistical Manual of Mental Disorders [DSM-V] or in the opinion of the investigator) within the last two years, or a positive urine drug screen for cocaine, heroin, or marijuana.
    -Known history of HIV infection
    -Any planned surgeries requiring general anaesthesia, or
    hospitalisation for more than 1 day during the study period
    -Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control
    -For male patients: Men who are able to father a child, unwilling to be abstinent or to use an adequate form of effective contraception for the duration of study participation and for at least 28 days after treatment has ended.
    -Use of any investigational drug or procedure for other indications
    within 3 months or 6 half-lives (whichever is longer) prior to
    randomization.
    -Intake of medications which might interfere with the study drug
    within 3 months prior to randomization and intended to be initiated during the duration of the trial
    -Known hypersensitivity to the drug product excipients
    1.Deficit cognitivo lieve con eziologia diversa da AD in stadio prodromico (sulla base dei dati clinici e/o risultati attuali di laboratorio e/o referto pregresso MRI o CT cerebrale risalente ad un massimo di 12 mesi prima della visita di screening
    2.Rilevante patologia cerebrovascolare concomitante (definite da anamnesi di infarto/emorragia intra-craniale) temporalmente correlata all’inizio del decadimento cognitivo secondo il giudizio dello sperimentatore.
    3.Anamnesi di cancro (eccetto carcinoma delle cellule basali) e/o trattamento per cancro negli ultimi 5 anni.
    4.Anamnesi o diagnosi di qualunque delle seguenti condizioni sintomatiche e instabili/incontrollate secondo il giudizio dello sperimentatore:
    a.Patologia cardiovascolare incontrollata
    b.Patologia cardiaca ischemica significativa, infarto del miocardio negli ultimi 2 anni e/o con angina residua, ortopnea, defetti di conduzione (ECG), o qualunque altro difetto cardiaco significativo classificato secondo la New York Heart Association (NYHA) come di grado III o IV.
    c.Patologia epatica significativa
    d.Disturbi gastrointestinali significativi secondo il giudizio dello sperimentatore
    e.Patologia endocrina incontrollata quale diabete mellito o ipertiroidismo.
    f.Depressione maggiore incontrollata o instabile.
    g.Patologia polmonare significativa incline all’ipossia.
    h.Disturbi di natura immunologica come allergie clinicamente significative, Lupus eritematosus, o schleroderma.
    i.Patologia ematologica incontrollata / instabile, di qualunque eziologia, come anemia o mielo-soppressione refrattarie.
    J.Disfunzioni d’organo sistemiche o multiple che, secondo lo sperimentatore, avrebbero impatto sull’endpoint primario e secondario dello studio, come la disidratazione clinicamente rilevante.
    5.Insufficienza renale di grado severo, definita da GFR < 30ml/min/1.73m2 come da referto del laboratorio centralizzato, allo screening
    6.Qualunque altro disturbo psichiatrico quale schizofrenia o ritardo mentale.
    7.Qualunque atto suicida negli ultimi 2 anni.
    8.Qualunque ideazione suicidaria del tipo 4 o 5 come da Columbia Suicide Severity Rating Scale (CSSRS) negli ultimi 3 mesi
    9.Previa partecipazione a studi clinici con farmaco sperimentale per disturbi cognitivi di grado lieve. Il trattamento corrente con farmaci da banco, vitamine o altre formulazioni nutrizionali è consentita, ma devono essere registrati nella e-CRF.
    10.Storia significativa di dipendenza da o abuso di droghe, incluso alcol
    11.Nota infezione da HIV.
    12.Qualunque chirurgia pianificata che richieda anestesia generale od ospedalizzazione per più di1 giorno durante il periodo dello studio.
    13.Donne in pre-menopausa (ultima mestruazione ≤ 1 anno prima del consenso informato) che:
    -stiano allattando o incinta o
    -siano in età fertile e non usino (o non pianifichino di usare, per la durata dello studio e fino a 28 giorni dall’assunzione dell’ultima dose di trattamento)
    14.Per pazienti di sesso maschile: gli uomini in grado di concepire, se non disponibili all’astinenza o ad usare una forma adeguatamente efficace di contraccezione per tutta la durata dello studio e per almeno 28 giorni dall’ultima assunzione di trattamento dello studio.
    15.Utilizzo di qualunque farmaco o procedura sperimentale per altre indicazioni entro 3 mesi o 6
    T ½ (Half-lives) - la più lunga- prima della randomizzazione.
    16.Assunzione dei seguenti entro 3 mesi dalla randomizzazione e se da iniziarsi durante lo studio:
    a.antidepressivi triciclici
    b.antidepressivi inibitori delle mono-amino-ossidasi
    c.neurolettici con azione anticolinergica moderata o forte (clororpromazina cloridrato, flufenazina, loxapina, perfenazina, thioridazina)
    d.anticolinergici
    I seguenti farmaci sono consentiti al bisogno, qualora la dose totale giornaliera sia rimasta stabile per 8 settimane prima della randomizzazione e ci si aspetta che rimanga tale per la durata dello studio:
    -Neurolettici, benzodiazepine e sedativi elencati nella sezione sez. 4.2.2
    17.Indicazione di disfunzione epatica definita dai livelli serici di ALT (SGPT), AST (SGOT), o fosfatasi alcalina oltre 3 volte il limite superiore di normalità, come determinato durante le visite dello studio.
    18.Qualunque altra condizione clinica che a giudizio dello sperimentatore metterebbe a rischio la sicurezza del paziente mentre partecipa allo studio.
    19.Non-compliance con l’assunzione del farmaco sperimentale durante il periodo di run-in con placebo (compliance < 75 %)
    20.Perdita dell’udito non compensata, clinicamente significativa a giudizio dello sperimentatore . E’ consentito l’utilizzo di dispositivi per l’udito.
    21.Nota ipersensibilità agli eccipienti del farmaco sperimentale (lattosio monoidrato, cellulosa microcristallina, amido pre-gelatinizzato, idrossipropil-cellulosa, croscarmellosa sodica, magnesio stearato, glicole propilenico, titanio diossido, talco e giallo da ossido di ferro).
    E.5 End points
    E.5.1Primary end point(s)
    1: The primary endpoint is Neuropsychological Test Battery (NTB) response, defined as
    change from baseline in total score after 12-week treatment.
    1) L'endpoint primario è la risposta al test cognitivo neuropsicologico di Battery (NTB), definita come variazione dal basale del punteggio totale dopo 12 settimane di trattamento.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1: 12 weeks
    1) 12 settimane
    E.5.2Secondary end point(s)
    1: Change from baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients) total score after 12-week treatment.
    2: Change from baseline in ADCS-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living) total score after 12-week treatment.
    3: Change from baseline CDR-SB (Clinical Dementia Rating, Sum of Boxes) after 12-week treatment
    4: Change from baseline in ADAS-Cog11 (Alzheimers Disease Assessment Scale cognitive subscale) total score after 12-week treatment.
    1) Cambiamento dal basale nel punteggio totale della scala “Alzheimer's Disease Cooperative Study/Activities of Daily Living” (ADCS-MCI-ADL) adattata per I pazienti MCI, dopo 12 settimane di trattamento.
    2) Cambiamento dal basale nel punteggio totale del “Alzheimer's Disease Cooperative Study/Activities of Daily Living” (ADCS-ADL), dopo 12 settimane di trattamento.
    3) Variazione dal basale del “Clinical Dementia Rating-Sum of Boxes” (CDR-SB), dopo un trattamento di 12 settimane
    4) Cambiamento dal basale nel punteggio totale del “Alzheimers Disease Assessment Scale cognitive subscale” (ADAS-Cog11), dopo 12 settimane trattamento.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1: 12 weeks
    2: 12 weeks
    3: 12 weeks
    4: 12 weeks
    12 settimane, per tutti gli endpoint
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    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 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 trial5
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA44
    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
    Austria
    Belgium
    Canada
    France
    Germany
    Italy
    Netherlands
    Poland
    Portugal
    Spain
    United Kingdom
    United States
    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 years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    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: 700
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 300
    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 state52
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 740
    F.4.2.2In the whole clinical trial 1000
    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
    Nessuno
    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 Decision2015-01-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-12-11
    P. End of Trial
    P.End of Trial StatusCompleted
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