E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate Alzheimer's disease |
Enfermedad de Alzheimer en estadío moderado |
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E.1.1.1 | Medical condition in easily understood language |
moderate Alzheimer's disease |
Enfermedad de Alzheimer en estadío moderado |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
Evaluar la eficacia de 3 dosis fijas de S38093 (2, 5, y 20 mg/dia) frente a placebo asociado a donepezilo (10 mg/día) en la función cognitiva mediante la escala ADAS-Cog de 11 puntos tras 24 semanas de tratamiento |
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E.2.2 | Secondary objectives of the trial |
Efficacy and safety |
Evaluar la eficacia de 3 dosis de S38093 (2, 5 y 20 mg/dia) frente a placebo asociado a donepezilo (10 mg/dia) en la función cognitiva y síntomas neuropsiquiátricos mediante otras escalas : la DAD, MMSE, ADCS-CGI e inventario NPI tras 24 semanas de tratamiento y Evaluar la seguridad de S3809 frentea placebo asociado a donepezilo tras 24 semanas de tratamiento |
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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. |
Pacientes ambulatorios entre 55 y 85 años con un nivel de escolarización? 4años, con deterioro cognitivo (criterios DSM-IV-TR para el diagnóstico de demencia tipo Alzheimer y criterios NINCDS/ADRDA para el diagnóstico de probable EA) con una MMSE de entre 12-20, con una puntuación? 5 en la escala de depresión geriátrica y ? 4 para la escala de isquemia de Hachinski modificada que hayan estado tratados con donepezilo en los últimos 4 meses y con una dosis estable de 10 mg/dia en los últimos 3 meses. Deben tener además un cuidador responsable que conozca al paciente desde al menos 1 año y que esté en contacto con él un mínimo de 10 h/semana |
|
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. |
Pacientes ingresados (hospitalizados o ingresados en alguna institución) pacientes incapaces de leer o escribir, mujeres en edad fértil (no postmenopáusicas durante al menos los dos años previos a la visita de selección o sin histerectomia), ausencia del cuidador, demencia debida a cualquier otra enfermedad diferente a la enfermedad de Alzheimer, historia previa de epilepsia o convulsión aislada, e esquizofrenia, trastorno esquizoafectivo o trastorno bipolar, trastorno depresivo mayor en los dos meses previos a la inclusión. Pacientes con EA y síntomas depresivos estables asociados (estables durante al menos dos meses previos a la inclusión) si podrían seleccionarse |
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E.5 End points |
E.5.1 | Primary end point(s) |
Alzheimer?s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) 11 items |
Subescala Cognitiva de evaluación de la enfermedad de Alzheimer (ADAS-Cog) de 11 puntos |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
W0, W12 and W24 |
Visitas W0 (inclusión), W12 (semana 12 tras inclusión)y W24 (semana 24 trás inclusión) |
|
E.5.2 | Secondary end point(s) |
Disability Assessment for Dementia (DAD) |
Eficacia: Escala de Evaluación de la discapacidad en demencia (DAD), escala mental breve (MMSE), Escala de impresión clinica a cerca de los cambios generales (ADCS-CGIC), Inventario neuropsiquiátrico (NPI), Escala para medir la carga del cuidador (Zarit Burden Inventory). Seguridad: acontecimientos adversos, signos vitales, ECG, análisis de laboratoeio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
W0 and W24 |
Criterios de eficacia en W0 (visita de inclusión), W12 (semana 12) y W24 (semana 24). Criterios de seguridad en todas las visitas del protocolo ASSE, W0, W4, W12, W24, WEND en los contactos teléfónicos se les preguntará a pacientes y cuidadores por posibles acontecimientos adversos que hayan podido tener |
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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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 15 |
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 |
Austria |
Brazil |
Canada |
Finland |
Germany |
Italy |
Mexico |
Poland |
Portugal |
Slovakia |
Spain |
Sweden |
United Kingdom |
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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
|
LVLS |
última visita del último paciente incluido |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |