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 evaluate the long-term safety and tolerability of Lu AE58054 as adjunctive therapy to donepezil in patients with mild-moderate AD. |
Valutare la sicurezza e la tollerabilità a lungo termine di Lu AE58054 come terapia aggiuntiva a donepezil in pazienti affetti da malattia di Alzheimer da lieve a moderata. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the disease development during long-term treatment with Lu AE58054 as adjunctive therapy to donepezil. |
Valutare lo sviluppo della malattia durante il trattamento a lungo termine con Lu AE58054 come terapia aggiuntiva a donepezil. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The patient has completed Visit 7 (Completion Visit) in the lead-in double-blind, placebo controlled clinical studies 14861A or 14862A. |
• Il paziente ha completato la visita 7 (visita di conclusione) degli studi clinici lead-in, in doppio cieco, controllati contro placebo, 14861A o 14862A. |
|
E.4 | Principal exclusion criteria |
• The patient has a moderate or severe ongoing adverse event from the lead-in study considered a potential safety risk by the investigator.
• The patient has experienced seizures before Completion Visit in the lead-in study.
• The patient has evidence of clinically significant disease.
• The patient's donepezil treatment is likely to be interrupted or discontinued during the study.
• The patient is receiving therapy with another AChEI or memantine. |
• Il paziente manifesta un evento avverso in corso, moderato o grave, insorto durante lo studio lead-in, che lo sperimentatore considera essere un rischio potenziale per la sicurezza.
• Il paziente ha sperimentato convulsioni prima della Visita di Conclusione dello studio lead-in.
• Il paziente ha evidenza di malattia clinicamente significativa.
• Il trattamento con donepezil del paziente rischia di essere interrotto o è interrotto durante lo studio.
• Il paziente è in terapia con un altro AChEI e/o memantina. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Safety: Number of adverse events
• Tolerability: Number of withdrawals |
- Sicurezza: numero di eventi avversi
- Tollerabilità: numero di ritiri
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 28 weeks and a 4-week safety follow-up |
fino a 28 settimane e al follow-up di sicurezza a 4 settimane |
|
E.5.2 | Secondary end point(s) |
• Change in cognition: Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score
• 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 cognitive aspects of mental function: Change in Mini Mental State Examination (MMSE)
• Risk of Suicidality Using C-SSRS Scores: Columbia Suicide Severity Rating Scale (C-SSRS) |
- Variazione delle capacità cognitive: Variazione del punteggio totale della sottoscala cognitiva ADAS-Cog (Alzheimer's Disease Assessment Scale cognitive subscale)
- Variazione impressione globale: Punteggio della scala ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change)
- Variazione di funzionamento: Variazione del punteggio totale della scala ADCS-ADL23 (Alzheimer's Disease Cooperative Study - - Variazione disturbi comportamentali: Variazione del punteggio totale del Neuropsychiatric Inventory (NPI)
- Variazione aspetti cognitivi della funzione mentale: Variazione del Mini Mental State Examination (MMSE)
- rischio di suicidio utilizzando i punteggi C-SSRS: Columbia Suicide Severity Rating Scale (C-SSRS)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 28 for all, except for Risk of Suicidality which is up to week 28. |
basale e settimana 28 per tutti, ad eccezione del rischio di suicidio, per cui è sino a settimana 28 |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 108 |
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 |
Belgium |
Bulgaria |
Canada |
Denmark |
France |
Ireland |
Italy |
Croatia |
Portugal |
Romania |
Argentina |
Brazil |
Chile |
Czech Republic |
Estonia |
Finland |
Germany |
Korea, Republic of |
Lithuania |
Spain |
Israel |
Poland |
South Africa |
Taiwan |
Ukraine |
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 | 4 |
E.8.9.1 | In the Member State concerned days | 9 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 9 |