Efficacy and Safety of 3 Doses of S47445 Versus Placebo in Patients With Alzheimer's Disease at Mild to Moderate Stages With Depressive Symptoms

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy and Safety of 3 Doses of S47445 Versus Placebo in Patients With Alzheimer's Disease at Mild to Moderate Stages With Depressive Symptoms. A 24-week International, Multi-centre, Randomized, Double-blind, Placebo-controlled Phase II Study in Monotherapy Followed by an Optional 28-week Extension Period in Co-administration With Donepezil.

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: S47445 5mg
* Drug: S47445 15mg
* Drug: S47445 50mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S47445 5mg<br> | Drug: S47445 5mg<br>* 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).<br>|
| Experimental: S47445 15mg<br> | Drug: S47445 15mg<br>* 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).<br>|
| Experimental: S47445 50mg<br> | Drug: S47445 50mg<br>* 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).<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on 11-item ADAS-Cog | Cognition criterion | 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activities of Daily Living: Disability Assessment for Dementia (DAD) | Key secondary efficacy criterion | baseline, week 12, week 24 and week 52 | 
| Cognition: 13-item ADAS-Cog | Other secondary efficacy criteria | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Cognition: Mini-Mental State Examination (MMSE) | Other secondary efficacy criteria | baseline, week 12, week 24 and week 52 | 
| Depressive symptoms: Cornell Scale for Depression in Dementia (CSDD) | Other secondary efficacy criteria | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Behavioural signs and symptoms: Neuropsychiatric Inventory (NPI) | Other secondary efficacy criteria | baseline, week 4, week 12, week 24 and week 52 | 
| Global Clinic Assessment of Change: Alzheimer's Disease Cooperative Studies-Clinical Global Impression of Change (ADCS-CGIC) | Other secondary efficacy criteria | baseline, week 24 and week 52 | 
| Functionality: Gait task (GT), measure of speed of walking (unit= meters/ seconds) | Other secondary efficacy criteria | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Adverse events | Safety criterion | through study completion, an average of 1 year | 
| Vital signs: heart rate | Safety criterion | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Vital signs: body temperature | Safety criterion | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Vital signs: blood pressure | Safety criterion | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Vital signs: body weight | Safety criterion | baseline, week 12, week 24, week 38 and week 52 | 
| 12-lead ECG | Safety criterion | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Biological laboratory parameters: number of participants with abnomal laboratory values | Safety criterion | baseline, week 4, week 12, week 24, week 38 and week 52 | 
| Cornell Scale for Depression in Dementia (CSDD, suicide item - item 16) | Safety criterion | baseline, week 4, week 12, week 24, week 28, week 38 and week 52 |