Mild to moderate Alzheimer's disease in patients with depressive symptoms MedDRA version: 19.0 Level: PT Classification code 10012296 Term: Dementia of the Alzheimer's type, with depressed mood System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Out-patients - Age 55-85 years - Able to perform neuropsychological tests - Have a responsible informant - DSM-IV-TR criteria for Dementia of the Alzheimer’s Disease Type - Mini mental State Examination (MMSE) = 15-24 both inclusive - National Institute of Mental Health (NIMH) provisional criteria for depression in AD (NIMH-dAD) - Cornell Scale for Depression in Dementia total score > or = 8 - Patients who have never been treated with AD treatments or patients who have stopped AD treatment whatever the reason - Patients either not currently treated with an antidepressant or patients being treated with an antidepressant at the recommended dose for at least 8 weeks without clinical efficacy, who can stop this treatment according to the investigator’s opinion. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 420
Exclusion criteria
Exclusion criteria: - Patients not able to read or write - Patients having participated in a study testing disease modifying therapy for AD, or in another study with administration of investigational drug or device within the previous 3 months prior to selection visit - Depressive symptoms that, in investigator’s judgment, are clearly due to a medical condition other than AD, or are a direct result of non-mood related dementia symptoms - History of epilepsy or solitary seizure - Medical history of Major Depressive Disorder more than 3 years before onset of the disease, treated with antidepressive drugs or electroconvulsive therapy - Severe or unstable disease of any type that could interfere with safety and efficacy assessments - Alcohol abuse or drug abuse or addiction, as judged by the clinician (excluding nicotine) - Clinically relevant lactose intolerance - Antidepressant treatment not stopped for at least 3 weeks before inclusion - Significant worsening of depressive symptoms or high suicidal risk according to investigator's judgement - For optional extension phase: ° Medically instable Chronic Obstructive Pulmonary Disease and asthma ° known hypersensitivity to donepezil hydrochloride or piperidine derivatives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Assessment of efficacy of 3 doses of S 47445 versus placebo on cognitive performance measured with the 11-item ADAS-Cog after 24 weeks of treatment ;Secondary Objective: Key secondary objective : -Assessment of efficacy of 3 doses of S 47445 versus placebo, after 24 weeks of treatment, on activities of daily living considering the Disability Assessment for Dementia (DAD) Secondary objectives : - Assessment of efficacy of 3 doses of S 47445 versus placebo on cognitive performance measured by other criteria, depressive symptoms, neuropsychiatric symptoms, clinical global impression of change and functionality after 24 weeks of treatment - Assessment of safety and tolerance of 3 doses of S 47445 after 24 and 52 weeks of treatment - To provide S 47445 safety/tolerance and efficacy data in co-administration with donepezil after 28 weeks of treatment - Assessment of pharmacokinetics of S47445 and/or its metabolites ;Primary end point(s): - 11-item ADAS-Cog after 24 weeks of treatment;Timepoint(s) of evaluation of this end point: At W000, W004, W012, W024, W038 and W052 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary efficacy criterion : - Activities of Daily Living : Disability Assessment for Dementia (DAD) Other secondary efficacy criteria : - Cognition : - 13-item ADAS-Cog - Mini-Mental State Examination (MMSE) - Depressive symptoms : Cornell Scale for Depression in Dementia (CSDD) - Behavioural signs and symptoms : Neuropsychiatric Inventory (NPI) - Global Clinic Assessment of Change : Alzheimer's Disease Cooperative Studies-Clinical Global Impression of Change (ADCS-CGIC) - Functionality : Gait task (GT) Safety criteria : - Adverse events - Vital signs: heart rate, body temperature, blood pressure, body weight - Physical examination - 12-lead ECG - Biological laboratory parameters - CSDD (suicide item - item 16) ;Timepoint(s) of evaluation of this end point: - DAD : at W000, W012, W024 and W052 - 13-item ADAS-Cog : at W000, W004, W012, W024, W038 and W052 - MMSE : at W000, W012, W024 and W052 - CSDD : at W000, W004, W012, W024, W038 and W052 - NPI : at W000, W004, W012, W024 and W052 - ADCS-CGIC : W0, W24, W52 - GT : at W000, W004, W012, W024, W038 and W052 - Adverse events : all over the study - Vital signs : blood pressure, heart rate and body temperature at W000, W004, W012, W024, W038 and W052 and body weight at W000, W012, W024, W038 and W052 - Physical examination : at W000, W004, W012, W024, W038 and W052 - 12-lead ECG : at W000, W004, W012, W024, W038 and W052 - Biological laboratory parameters : at W000, W004, W012, W024, W038 and W052 - CSDD (suicide item - item 16) at all visits | — |
Countries
Brazil, Bulgaria, Chile, Czech Republic, Germany, Hungary, Japan, Mexico, Poland, Russian Federation, Slovakia, South Africa
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed