Efficacy and safety of 3 doses of S 47445 versus placebo in patients with Alzheimer's disease at mild to moderate stages with depressive symptoms

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2014-001519-38-HU
• Date of registration: 15/10/2014
• Prospective Registration: Yes
• Primary sponsor: Institut de Recherches Internationales Servier
• Public title: Efficacy and safety of 3 doses of S 47445 versus placebo in patients with Alzheimer's disease at mild to moderate stages with depressive symptoms
• Scientific title: Efficacy and safety of 3 doses of S 47445 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.
• Date of first enrolment: 04/12/2014
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001519-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Bulgaria, Chile, Czech Republic, Germany, Hungary, Japan, Mexico, Poland, Romania, Russian Federation, Slovakia, South Africa, Ukraine

Contacts

• Name: Clinical Studies Department
• Affiliation: Institut de Recherches Internationales Servier

• Name: Clinical Studies Department
• Affiliation: Institut de Recherches Internationales Servier

Key inclusion & exclusion 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:
- 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild to moderate Alzheimer's disease in patients with depressive symptoms
MedDRA version: 18.1 Level: PT Classification code 10012296 Term: Dementia of the Alzheimer's type, with depressed mood System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: S47445
Product Code: S47445
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: S47445
Other descriptive name: S47445
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S47445
Product Code: S47445
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: S47445
Other descriptive name: S47445
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S47445
Product Code: S47445
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: S47445
Other descriptive name: S47445
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): - 11-item ADAS-Cog after 24 weeks of treatment

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

Timepoint(s) of evaluation of this end point: At W000, W004, W012, W024, W038 and W052

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

Secondary Outcome(s)

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

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)

Secondary ID(s)

CL2-47445-011

2014-001519-38-DE

Source(s) of Monetary Support

ADIR