E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate Alzheimer's disease |
Malattia di Alzheimer di grado moderato |
|
E.1.1.1 | Medical condition in easily understood language |
Moderate Alzheimer's disease |
Malattia di Alzheimer di grado moderato |
|
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 | 15.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 assess the efficacy of 3 fixed doses of S 38093 (2, 5 and 20mg/ day) versus placebo, in co-administration with donepezil 10 mg/day, after 24 weeks of treatment, on cognitive performance measured with the ADAS-Cog 11-items in patients with moderate Alzheimers' Disease |
Valutare l’efficacia di 3 dosi prestabilite di S 38093 (2, 5 e 20 mg/die) verso placebo, in co–amministrazione con il donepezil 10 mg/die in pazienti con Alzheimer di grado moderato dopo un periodo di 24 settimane, sulle capacità cognitive valutate tramite la scala di valutazione ADAS-Cog ad 11 item. |
|
E.2.2 | Secondary objectives of the trial |
Efficacy and Safety |
Valutare l'efficacia e la sicurezza |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 55-85 years (both inclusive) -School education ≥ 4 years (i.e. formal schooling), -DSM-IV-TR criteria for Dementia of the Alzheimer’s Type . Memory impairment and . One or more cognitive disturbances: Aphasia, apraxia, agnosia or disturbance in executive functioning. . Significant impairment of social or occupational functioning due to cognitive deficits, with a decline from previous functioning, . Gradual onset of disease and continuous cognitive decline, . Deficit not due to delirium or any other medical cause. -NINCDS-ADRDA criteria for probable AD . Dementia established by clinical and confirmed by neuropsychological examination, . Progressive cognitive impairment, . Cognitive impairment in two or more areas of cognition, . Absence of other diseases possibly inducing dementia. -Total score of Mini-Mental State Examination (MMSE) between 12 and 20, both inclusive. Modified Hachinski Scale ≤ 4, -Geriatric Depression Rating Scale-15 (GDS) score ≤ 5 -Donepezil treatment (tablets of 5 or 10 mg/d) for at least 4 months before selection, and at a stable dose of 10 mg/day for at least 3 months before the selection visit |
Età compresa o uguale: 55-85 anni -Scolarità ≥ 4 anni -Criteri DSM-IV-TR per la demenza di tipo Alzheimer: *Deterioramento della memoria e uno o più dei seguenti disturbi cognitivi: Afasia, aprassia, agnosia o disturbo delle capacità funzionali esecutive, *Significativo deterioramento della funzionalità sociale o occupazionale a causa del deterioramento cognitivo, con un declino delle precedenti capacità funzionali,*Manifestazione graduale della patologia e declino cognitivo continuo, *Deficit non riconducibile a delirium o altre cause cliniche - Criteri del NINCDS-ADRDA per diagnosi di probabile malattia di Alzheimer.Demenza diagnosticata con esame clinico e confermata da valutazione neuropsicologica *Deterioramento cognitivo progressivo *Deterioramento cognitivo in due o più aree cognitive *Assenza di altre patologie che potrebbe potenzialmente portare alla demenza -Punteggio totale del Mini-Mental State Examination (MMSE) compreso tra 12 e 20(compresi) -Altri criteri: Punteggio della Scala di Hachinski modificata ≤ 4*Punteggio della Scala Geriatric Depression Rating -15 (GDS) ≤ 5. -Donepezil 10 mg per un periodo di almeno 4 mesi in cui il dosaggio deve essere stabile a 10 mg – negli ultimi 3 mesi prima della data di selezione |
|
E.4 | Principal exclusion criteria |
In-patients (e.g. hospitalised patients, institutionalised patients [patients in day care centers or in institutions where only meals and medications are provided, can be selected]), - Patients not being able to read or write before onset of Alzheimer's Disease, - Female patients of child-bearing potential (e.g., not menopausal for at least 2 years prior to selection or not having had hysterectomy), - Dementia due to any condition other than AD - History of epilepsy or solitary seizure (generalised or partial), Schizophrenia, Schizoaffective Disorder, Bipolar Disorders, - Major depressive disorder within the two months prior to inclusion. Patients with AD and associated stable depressive symptoms (stable for at least 2 months prior to inclusion) can be selected. |
-Pazienti ricoverati (in ospedale od in istituti di cura), tuttavia i pazienti ospitati in case di cura dove vengono assistiti solo per i pasti e la somministrazione delle medicine possono essere selezionati. -Pazienti incapaci a leggere o scrivere prima dell’insorgenza della malattia di Alzheimer. -Donne in età fertile (per esempio in menopausa da meno di 2 anni e non isterectomizzate) -Demenza dovuta a qualunque altra condizione che non sia la malattia di Alzheimer -storia di epilessia o episodio singolo di convulsioni, (generale o parziale) -Schizofrenia, Disturbo schizo-affettivo, Disturbo Bipolare -Depressione maggiore nei 2 mesi precedenti all’inclusione - pazienti affetti da Alzheimer con sintomi depressivi stabili associati (stabili da almeno 2 mesi prima dell'inclusione) possono essere selezionati. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) 11 items |
ADAS-Cog: Scala di Valutazione dell’Alzheimer – sottoscala Cognitivo a 11 items |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
W0, W12 and W24 |
Alle settimane 0, 12 e 24 |
|
E.5.2 | Secondary end point(s) |
Disability Assessment for Dementia (DAD) |
Valutazione della disabilità per demenza (DAD) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
W0 and W24 |
Alla settimana 0 e 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Mexico |
|
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
|
Last visit last subject |
Ultima visita dell'ultimo soggetto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 26 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 29 |
E.8.9.2 | In all countries concerned by the trial days | 0 |