E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer´s Disease |
Malattia di Alzheimer |
|
E.1.1.1 | Medical condition in easily understood language |
Alzheimer´s Disease |
Malattia di Alzheimer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the efficacy of Lu AE58054 as adjunctive therapy to donepezil for symptomatic treatment of patients with mild-moderate Alzheimer’s disease (AD). |
Stabilire l'efficacia di Lu AE58054 come terapia aggiuntiva a donepezil per il trattamento sintomatico di pazienti affetti da malattia di Alzheimer da lieve a moderata. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of Lu AE58054 as adjunctive therapy to donepezil on neuropsychiatric symptoms in patients with mild-moderate AD.
• To evaluate the safety and tolerability of Lu AE58054 as adjunctive therapy to donepezil in patients with mild-moderate AD.
|
• Valutare l'effetto che Lu AE58054, come terapia aggiuntiva a donepezil, produce sui sintomi neuropsichiatrici in pazienti affetti da malattia di Alzheimer da lieve a moderata.
• Valutare la sicurezza e la tollerabilità di AE58054, come terapia aggiuntiva a donepezil in pazienti affetti da malattia di Alzheimer da lieve a moderata.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The patient has a knowledgeable and reliable caregiver.
• The patient is an outpatient.
• The patient has probable AD.
• The patient has mild to moderate AD.
• Stable treatment with donepezil.
• The patient, if a woman, must have had her last natural menstruation ≥24 months prior to baseline, OR be surgically sterile.
• The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential, OR must have been surgically sterilised prior to the screening visit. |
• Il paziente ha una persona che presta le cure esperta e affidabile.
• Il paziente è un paziente ambulatoriale.
• Il paziente ha una diagnosi di probabile malattia di Alzheimer.
• Il paziente è affetto da malattia di Alzheimer da lieve a moderata.
• Il paziente è in trattamento stabile con donepezil.
• Il paziente di sesso femminile deve aver avuto l'ultimo ciclo mestruale naturale 24 mesi o più prima del baseline, o deve essere stato sottoposto a sterilizzazione chirurgica.
• I pazienti di sesso maschile acconsentono ad utilizzare un metodo contraccettivo efficace come definito da protocollo, se la compagna è potenzialmente fertile OPPURE devono essere stati sottoposti a sterilizzazione chirurgica prima della visita di screening.
|
|
E.4 | Principal exclusion criteria |
• The patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD.
• The patient has a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) Axis I disorder other than AD.
• The patient has evidence of clinically significant disease.
• The patient's donepezil therapy is likely to be interrupted or discontinued during the study.
• The patient is currently receiving memantine or has taken memantine within 2 months prior to screening. |
• Il paziente mostra evidenza di qualsiasi malattia neurodegenerativa clinicamente significativa o di altri disturbi neurologici gravi diversi dalla malattia di Alzheimer.
• Il paziente soffre di un disturbo dell'asse I secondo il DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, Manuale diagnostico e statistico dei disturbi mentali, quarta edizione, revisione del testo) diverso dalla malattia di Alzheimer.
• Il paziente mostra evidenza di una malattia clinicamente significativa
• È probabile che la terapia a base di donepezil del paziente venga interrotta o sospesa durante lo studio.
• Il paziente è trattato attualmente con memantina o ha assunto memantina nei 2 mesi precedenti alla visita di screening.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in cognition: Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. |
Variazione facoltà cognitive: variazione del punteggio totale ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale, Sottoscala cognitiva della scala per la valutazione della malattia di Alzheimer) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 24. |
basale e settimana 24 |
|
E.5.2 | Secondary end point(s) |
• Change in global impression:Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score
• Change in functioning: Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score
• Change in behavioural disturbance: Change in Neuropsychiatric
Inventory (NPI) total score
• Change in individual behavioural disturbance items: Change in single NPI item scores
• Change in anxiety: Change in NPI Anxiety item score based on a pre-specified NPI Anxiety score at Baseline
• Clinical response: Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes
• Clinical worsening: Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes
• Change in cognitive aspects of mental function: Change in Mini Mental State Examination (MMSE)
• Change in health-related quality of life (EQ-3D-5L): Change in EuroQol 5-dimensional 3-layer (EQ-5D-3L), a measure of health-related quality of life
• Change in health-related quality of (EQ-5D-3L VAS): Change in EQ-5D-3L Visual Analogue Scale (EQ-5D-3L VAS)
• Number of patients with adverse events (AEs): Overview of AEs
• Proportion of patients who withdrew due to intolerance to treatment
• Risk of suicidality: Columbia Suicide Severity Rating Scale (C-SSRS) |
• Variazione Impressione globale: Punteggio ADCS-CGIC (Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change, Studio cooperativo sulla malattia di Alzheimer - Impressione globale del medico sul cambiamento)
• Variazione Funzionalità: punteggio totale ADCS-ADL23 (Alzheimer’s disease Cooperative Study - Activities of Daily Living Inventory, Studio cooperativo sulla malattia di Alzheimer - inventario delle attività della vita quotidiana)
• Variazione nel disturbo comportamentale: punteggio totale NPI (Neuropsychiatric Inventory, Inventario neuropsichiatrico)
• Variazione nel disturbo comportamentale: variazione delle singole voci dell'NPI
• Variazione dell’ansia: variazione rispetto al basale nel punteggio delle voci relative all’ansia dell’NPI
• Risposta clinica: variazioni pre-specificate del punteggio ADAS-cog, ADCS-ADL23 e ADCS-CGIC
• Peggioramento clinico: variazioni pre-specificate del punteggio ADAS-cog, ADCS-ADL23 e ADCS-CGIC
• Variazione degli aspetti cognitivi della funzione mentale: variazione del punteggio MMSE (Mini Mental State Examination, Mini esame dello stato mentale)
• Variazione della qualità della vita in connessione alla salute (EQ-5D-3L): variazione dell’EQ-5D-3L, una misura della qualità della vita in connessione alla salute
• Variazione della qualità della vita in connessione alla salute: variazione della VAS (Visual Analogic Scale, Scala analogica visiva) dell'ED-5D-3L
• Numero di pazienti con eventi avversi (EA): panoramica EA
• Percentuale di pazienti che si sono ritirati a causa di intolleranza al trattamento
• Rischio di suicidio: scala C-SSRS (Columbia Suicide Severity Rating Scale)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 24 |
basale e settimana 24 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Ireland |
Italy |
Croatia |
Portugal |
Argentina |
Brazil |
Estonia |
Finland |
Korea, Republic of |
Lithuania |
Thailand |
Israel |
Poland |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |