Clinical trial NCT02626572: Efficacy and Safety of 3 Doses of S47445 Versus Placebo in Patients With Alzheimer's Disease at Mild to Moderate Stages With Depressive Symptoms
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2015-12-10
Enrollment: 500
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline on 11-item ADAS-Cog
timeFrame: 24 weeks of treatment
Secondary outcomes:
measure: Activities of Daily Living: Disability Assessment for Dementia (DAD)
timeFrame: baseline, week 12, week 24 and week 52
measure: Cognition: 13-item ADAS-Cog
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Cognition: Mini-Mental State Examination (MMSE)
timeFrame: baseline, week 12, week 24 and week 52
measure: Depressive symptoms: Cornell Scale for Depression in Dementia (CSDD)
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Behavioural signs and symptoms: Neuropsychiatric Inventory (NPI)
timeFrame: baseline, week 4, week 12, week 24 and week 52
measure: Global Clinic Assessment of Change: Alzheimer's Disease Cooperative Studies-Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: baseline, week 24 and week 52
measure: Functionality: Gait task (GT), measure of speed of walking (unit= meters/ seconds)
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Adverse events
timeFrame: through study completion, an average of 1 year
measure: Vital signs: heart rate
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Vital signs: body temperature
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Vital signs: blood pressure
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Vital signs: body weight
timeFrame: baseline, week 12, week 24, week 38 and week 52
measure: 12-lead ECG
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Biological laboratory parameters: number of participants with abnomal laboratory values
timeFrame: baseline, week 4, week 12, week 24, week 38 and week 52
measure: Cornell Scale for Depression in Dementia (CSDD, suicide item - item 16)
timeFrame: baseline, week 4, week 12, week 24, week 28, week 38 and week 52
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Trial Tech Tecnologia em Pesquisa com Medicamentos
city: Fortaleza
country: Brazil
facility: Hospital Universitario Walter Cantidio
city: Maringa
country: Brazil
facility: Clinilive - Centro de Pesquisas Clinicas
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Recife
country: Brazil
facility: Hospital Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Instituto Américo Bairral de Psiquiatria, Centro de Pesquisa
city: Sao Paulo
country: Brazil
facility: UNIFESP - Universidade Federal de Sao Paulo
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi
city: Sofia
country: Bulgaria
facility: Medical University of Sofia, Aleksandrovska hospital
city: Sofia
country: Bulgaria
facility: National Hospital of Cardiology
city: Sofia
country: Bulgaria
facility: University Hospital Sveti Naum, Clinic of Neurology
city: Varna
country: Bulgaria
facility: MHAT Sveta Marina
city: Antofagasta
country: Chile
facility: Clínica Oriente
city: Santiago
country: Chile
facility: Biomedica Research Group
city: Santiago
country: Chile
facility: Especialidades Medicas LYS
city: Santiago
country: Chile
facility: Hospital Santiago Oriente
city: Santiago
country: Chile
facility: Private practice
city: Brno
country: Czechia
facility: Saint Anne s.r.o. Psychiatricka ambulance
city: Kladno
country: Czechia
facility: Brain-Soultherapy s.r.o.
city: Litomerice
country: Czechia
facility: Bialbi s.r.o.
city: Praha
country: Czechia
facility: AD71 s.r.o. Psychiatricka ambulance - Sudkova
city: Praha
country: Czechia
facility: CLINTRIAL s.r.o.
city: Praha
country: Czechia
facility: FORBELI s.r.o., Neurologicka ambulance
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land GmbH Neurologische Klinik
city: Bochum
country: Germany
facility: Neuropsychiatrisches Facharztzentrum Stiepel
city: Homburg / Saar
country: Germany
facility: Universitaetsklinikum des Saarlandes, Klinik für Psychiatrie und Psychotherapie
city: Mannheim
country: Germany
facility: ISPG Institut für Studien zur Psychischen Gesundheit
city: Mittweida
country: Germany
facility: Pharmakologisches Studienzentrum Chemnitz GmbH
city: Schwerin
country: Germany
facility: Somni Bene, Institut fuer Medizinische Forschung und Schlafmedizin Schwerin GmbH
city: Ulm
country: Germany
facility: Universitaetsklinik ULM, Poliklinik Neurologie
city: Westerstede
country: Germany
facility: Private practice
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Neurologiai Klinika
city: Debrecen
country: Hungary
facility: Kenezy Gyula Korhaz es Rendelointezet
city: Esztergom
country: Hungary
facility: Vaszary Kolos Korhaz Esztergom Neurologiai Osztaly
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz Pszihiatriai, Mentalhygienes es Addiktologiai Osztaly
city: Kalocsa
country: Hungary
facility: Private practice
city: Miskolc
country: Hungary
facility: B-A-Z Megyei Korhaz es Egyetemi Oktato Korhaz Stroke, Er- es Neurologiai, Toxikologiai Osztaly
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Oktatokorhaz Pszihiatriai Osztaly
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem, Klinikai Kozpont Pszich. es Pszichoter. Klinika
city: Szeged
country: Hungary
facility: Szent-Gyorgyi Albert Klinikai Kozpont Pszichiatriai Klinika
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Pszichiatriai Osztaly
city: Bunkyo-ku
country: Japan
facility: Memory Clinic Ochanomizu
city: Kagoshima-shi
country: Japan
facility: Showakai Clinic
city: Karatsu-shi
country: Japan
facility: Rainbow & Sea Hospital
city: Kawasaki-shi
country: Japan
facility: Kokan Clinic
city: Nagoya
country: Japan
facility: Social Medical Corporation Kojunkai Daido Hospital
city: Nakano-ku
country: Japan
facility: Nakano General Hospital
city: Saitama-shi
country: Japan
facility: Private practice
city: Setagaya-ku
country: Japan
facility: Private practice
city: Toyoake-shi
country: Japan
facility: Seishinkai Okehazama Hospital
city: Aguascalientes
country: Mexico
facility: Instituto Biomedico de Investigacion
city: Monterrey
country: Mexico
facility: Centro de Estudios Clinicos Y Especialidades Medicas Sc
city: Nuevo León
country: Mexico
facility: Hospital Universitario de Nuevo León
city: Saltillo
country: Mexico
facility: University Hospital of Saltillo
city: Bydgoszcz
country: Poland
facility: Nzoz Centrum Kultury, Higieny I Zdrowia Psychicznego
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Centrum Neurologii Klinicznej
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M. Nastaj Sp. Partnerska
city: Scinawa
country: Poland
facility: Osrodek Alzheimerowski Sp. z o.o.
city: Sopot
country: Poland
facility: SENIOR Poradnia Psychogeriatryczna
city: Warszawa
country: Poland
facility: Centrum Medyczne Neuroprotect
city: Kazan
country: Russian Federation
facility: Interregional Clinico-Diagnostical Centre
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University n.a.I.M. Sechenov Clinic of Neurology
city: Moscow
country: Russian Federation
facility: Scientific Center of Mental Health Sect of AD and associated disord. Dpt of gerontopsychiatry
city: Moscow
country: Russian Federation
facility: Scientific Center of Mental Health Sect of psychosis of elderly ages Dpt of gerontopsychiatry
city: St. Petersburg
country: Russian Federation
facility: City geriatric medico-social centre
city: St. Petersburg
country: Russian Federation
facility: Medical Military Academy n.a.S.M.Kirov
city: St. Petersburg
country: Russian Federation
facility: Psychoneuropathology Dispensary N 10
city: Voronezh
country: Russian Federation
facility: Co Ltd "LION-MED"
city: Bratislava
country: Slovakia
facility: Private practice
city: Kosice
country: Slovakia
facility: INVESTA, spol. s r. o. Psychiatricka ambulancia
city: Roznava
country: Slovakia
facility: NsP Svatej Barbory Psychiatricke oddelenie
city: Bloemfontein
country: South Africa
facility: Iatros International
city: Cape Town
country: South Africa
facility: Flexivest Fourteen Research Centre
city: Durban
country: South Africa
facility: Umhlanga Hospital
city: George
country: South Africa
facility: Excellentis Clinical Trial Consultants
city: Johannesburg
country: South Africa
facility: Apollo Clinical Research
city: Pretoria
country: South Africa
facility: Denmar Hospital
city: Somerset West
country: South Africa
facility: Somerset West Trial Centre
Study officials:
References:
citation: Bernard K, Gouttefangeas S, Bretin S, Galtier S, Robert P, Holthoff-Detto V, Cummings J, Pueyo M. A 24-week double-blind placebo-controlled study of the efficacy and safety of the AMPA modulator S47445 in patients with mild to moderate Alzheimer's disease and depressive symptoms. Alzheimers Dement (N Y). 2019 Jun 24;5:231-240. doi: 10.1016/j.trci.2019.04.002. eCollection 2019.