Alzheimer's Disease
Conditions
Brief summary
The purpose of this trial is to assess the efficacy and safety of S47445 versus placebo in patients with Alzheimer's disease at mild to moderate stages with depressive symptoms. An optional 28-week extension period will be performed to evaluate safety/tolerance and efficacy of S47445 in co-administration with donepezil.
Interventions
DRUGS47445 5mg
S47445 5 mg tablets taken orally once a day during breakfast, starting the day after inclusion visit and ending the day of the W024 visit (main period) or starting the day after inclusion visit and ending the day of the W052 visit (period including main period and optional extension period).
DRUGS47445 15mg
S47445 15 mg tablets taken orally once a day during breakfast, starting the day after inclusion visit and ending the day of the W024 visit (main period) or starting the day after inclusion visit and ending the day of the W052 visit (period including main period and optional extension period).
DRUGS47445 50mg
S47445 50 mg tablets taken orally once a day during breakfast, starting the day after inclusion visit and ending the day of the W024 visit (main period) or starting the day after inclusion visit and ending the day of the W052 visit (period including main period and optional extension period).
DRUGPlacebo
Placebo tablets taken orally once a day during breakfast, starting the day after inclusion visit and ending the day of the W024 visit (main period) or starting the day after inclusion visit and ending the day of the W052 visit (period including main period and optional extension period).
Sponsors
Institut de Recherches Internationales Servier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Out-patients * 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.
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 judgment * 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 | Description |
|---|---|---|
| Change from baseline on 11-item ADAS-Cog | 24 weeks of treatment | Cognition criterion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognition: 13-item ADAS-Cog | baseline, week 4, week 12, week 24, week 38 and week 52 | Other secondary efficacy criteria |
| Cognition: Mini-Mental State Examination (MMSE) | baseline, week 12, week 24 and week 52 | Other secondary efficacy criteria |
| Depressive symptoms: Cornell Scale for Depression in Dementia (CSDD) | baseline, week 4, week 12, week 24, week 38 and week 52 | Other secondary efficacy criteria |
| Behavioural signs and symptoms: Neuropsychiatric Inventory (NPI) | baseline, week 4, week 12, week 24 and week 52 | Other secondary efficacy criteria |
| Global Clinic Assessment of Change: Alzheimer's Disease Cooperative Studies-Clinical Global Impression of Change (ADCS-CGIC) | baseline, week 24 and week 52 | Other secondary efficacy criteria |
| Functionality: Gait task (GT), measure of speed of walking (unit= meters/ seconds) | baseline, week 4, week 12, week 24, week 38 and week 52 | Other secondary efficacy criteria |
| Adverse events | through study completion, an average of 1 year | Safety criterion |
| Activities of Daily Living: Disability Assessment for Dementia (DAD) | baseline, week 12, week 24 and week 52 | Key secondary efficacy criterion |
| Vital signs: body temperature | baseline, week 4, week 12, week 24, week 38 and week 52 | Safety criterion |
| Vital signs: blood pressure | baseline, week 4, week 12, week 24, week 38 and week 52 | Safety criterion |
| Vital signs: body weight | baseline, week 12, week 24, week 38 and week 52 | Safety criterion |
| 12-lead ECG | baseline, week 4, week 12, week 24, week 38 and week 52 | Safety criterion |
| Biological laboratory parameters: number of participants with abnomal laboratory values | baseline, week 4, week 12, week 24, week 38 and week 52 | Safety criterion |
| Cornell Scale for Depression in Dementia (CSDD, suicide item - item 16) | baseline, week 4, week 12, week 24, week 28, week 38 and week 52 | Safety criterion |
| Vital signs: heart rate | baseline, week 4, week 12, week 24, week 38 and week 52 | Safety criterion |
Countries
Brazil, Bulgaria, Chile, Czechia, Germany, Hungary, Japan, Mexico, Poland, Russia, Slovakia, South Africa
Outcome results
None listed