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

Alzheimer's Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02626572
• Other study ID #: CL2-47445-011
• Secondary ID: 2014-001519-38
• Status: Completed
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: September 2017

Study information

• Verified date: August 2018
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Depression

Intervention

Drug:
• S47445 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).
• S47445 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).
• S47445 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).
• Placebo
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).

Locations

Country	Name	City	State
Brazil	Trial Tech Tecnologia em Pesquisa com Medicamentos	Curitiba
Brazil	Hospital Universitario Walter Cantidio	Fortaleza
Brazil	Clinilive - Centro de Pesquisas Clinicas	Maringa
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
Brazil	Hospital Oswaldo Cruz	Recife
Brazil	Instituto Américo Bairral de Psiquiatria, Centro de Pesquisa	Sao Paulo
Brazil	UNIFESP - Universidade Federal de Sao Paulo	Sao Paulo
Bulgaria	UMHAT Sveti Georgi	Plovdiv
Bulgaria	Medical University of Sofia, Aleksandrovska hospital	Sofia
Bulgaria	National Hospital of Cardiology	Sofia
Bulgaria	University Hospital Sveti Naum, Clinic of Neurology	Sofia
Bulgaria	MHAT Sveta Marina	Varna
Chile	Clínica Oriente	Antofagasta
Chile	Biomedica Research Group	Santiago
Chile	Especialidades Medicas LYS	Santiago
Chile	Hospital Santiago Oriente	Santiago
Chile	Private practice	Santiago
Czechia	Saint Anne s.r.o. Psychiatricka ambulance	Brno
Czechia	Brain-Soultherapy s.r.o.	Kladno
Czechia	Bialbi s.r.o.	Litomerice
Czechia	AD71 s.r.o. Psychiatricka ambulance - Sudkova	Praha
Czechia	CLINTRIAL s.r.o.	Praha
Czechia	FORBELI s.r.o., Neurologicka ambulance	Praha
Germany	Klinikum Altenburger Land GmbH Neurologische Klinik	Altenburg
Germany	Neuropsychiatrisches Facharztzentrum Stiepel	Bochum
Germany	Universitaetsklinikum des Saarlandes, Klinik für Psychiatrie und Psychotherapie	Homburg / Saar
Germany	ISPG Institut für Studien zur Psychischen Gesundheit	Mannheim
Germany	Pharmakologisches Studienzentrum Chemnitz GmbH	Mittweida
Germany	Somni Bene, Institut fuer Medizinische Forschung und Schlafmedizin Schwerin GmbH	Schwerin
Germany	Universitaetsklinik ULM, Poliklinik Neurologie	Ulm
Germany	Private practice	Westerstede
Hungary	Semmelweis Egyetem Neurologiai Klinika	Budapest
Hungary	Kenezy Gyula Korhaz es Rendelointezet	Debrecen
Hungary	Vaszary Kolos Korhaz Esztergom Neurologiai Osztaly	Esztergom
Hungary	Petz Aladar Megyei Oktato Korhaz Pszihiatriai, Mentalhygienes es Addiktologiai Osztaly	Gyor
Hungary	Private practice	Kalocsa
Hungary	B-A-Z Megyei Korhaz es Egyetemi Oktato Korhaz Stroke, Er- es Neurologiai, Toxikologiai Osztaly	Miskolc
Hungary	Josa Andras Oktatokorhaz Pszihiatriai Osztaly	Nyiregyhaza
Hungary	Pecsi Tudomanyegyetem, Klinikai Kozpont Pszich. es Pszichoter. Klinika	Pecs
Hungary	Szent-Gyorgyi Albert Klinikai Kozpont Pszichiatriai Klinika	Szeged
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Pszichiatriai Osztaly	Szekesfehervar
Japan	Memory Clinic Ochanomizu	Bunkyo-ku
Japan	Showakai Clinic	Kagoshima-shi
Japan	Rainbow & Sea Hospital	Karatsu-shi
Japan	Kokan Clinic	Kawasaki-shi
Japan	Social Medical Corporation Kojunkai Daido Hospital	Nagoya
Japan	Nakano General Hospital	Nakano-ku
Japan	Private practice	Saitama-shi
Japan	Private practice	Setagaya-ku
Japan	Seishinkai Okehazama Hospital	Toyoake-shi
Mexico	Instituto Biomedico de Investigacion	Aguascalientes
Mexico	Centro de Estudios Clinicos Y Especialidades Medicas Sc	Monterrey
Mexico	Hospital Universitario de Nuevo León	Nuevo León
Mexico	University Hospital of Saltillo	Saltillo
Poland	Nzoz Centrum Kultury, Higieny I Zdrowia Psychicznego	Bydgoszcz
Poland	Krakowska Akademia Neurologii Centrum Neurologii Klinicznej	Krakow
Poland	NZOZ Neuromed M. i M. Nastaj Sp. Partnerska	Lublin
Poland	Osrodek Alzheimerowski Sp. z o.o.	Scinawa
Poland	SENIOR Poradnia Psychogeriatryczna	Sopot
Poland	Centrum Medyczne Neuroprotect	Warszawa
Russian Federation	Interregional Clinico-Diagnostical Centre	Kazan
Russian Federation	First Moscow State Medical University n.a.I.M. Sechenov Clinic of Neurology	Moscow
Russian Federation	Scientific Center of Mental Health Sect of AD and associated disord. Dpt of gerontopsychiatry	Moscow
Russian Federation	Scientific Center of Mental Health Sect of psychosis of elderly ages Dpt of gerontopsychiatry	Moscow
Russian Federation	City geriatric medico-social centre	St. Petersburg
Russian Federation	Medical Military Academy n.a.S.M.Kirov	St. Petersburg
Russian Federation	Psychoneuropathology Dispensary N 10	St. Petersburg
Russian Federation	Co Ltd "LION-MED"	Voronezh
Slovakia	Private practice	Bratislava
Slovakia	INVESTA, spol. s r. o. Psychiatricka ambulancia	Kosice
Slovakia	NsP Svatej Barbory Psychiatricke oddelenie	Roznava
South Africa	Iatros International	Bloemfontein
South Africa	Flexivest Fourteen Research Centre	Cape Town
South Africa	Umhlanga Hospital	Durban
South Africa	Excellentis Clinical Trial Consultants	George
South Africa	Apollo Clinical Research	Johannesburg
South Africa	Denmar Hospital	Pretoria
South Africa	Somerset West Trial Centre	Somerset West

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier

Countries where clinical trial is conducted

Brazil,  Bulgaria,  Chile,  Czechia,  Germany,  Hungary,  Japan,  Mexico,  Poland,  Russian Federation,  Slovakia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline on 11-item ADAS-Cog	Cognition criterion	24 weeks of treatment
Secondary	Activities of Daily Living: Disability Assessment for Dementia (DAD)	Key secondary efficacy criterion	baseline, week 12, week 24 and week 52
Secondary	Cognition: 13-item ADAS-Cog	Other secondary efficacy criteria	baseline, week 4, week 12, week 24, week 38 and week 52
Secondary	Cognition: Mini-Mental State Examination (MMSE)	Other secondary efficacy criteria	baseline, week 12, week 24 and week 52
Secondary	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
Secondary	Behavioural signs and symptoms: Neuropsychiatric Inventory (NPI)	Other secondary efficacy criteria	baseline, week 4, week 12, week 24 and week 52
Secondary	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
Secondary	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
Secondary	Adverse events	Safety criterion	through study completion, an average of 1 year
Secondary	Vital signs: heart rate	Safety criterion	baseline, week 4, week 12, week 24, week 38 and week 52
Secondary	Vital signs: body temperature	Safety criterion	baseline, week 4, week 12, week 24, week 38 and week 52
Secondary	Vital signs: blood pressure	Safety criterion	baseline, week 4, week 12, week 24, week 38 and week 52
Secondary	Vital signs: body weight	Safety criterion	baseline, week 12, week 24, week 38 and week 52
Secondary	12-lead ECG	Safety criterion	baseline, week 4, week 12, week 24, week 38 and week 52
Secondary	Biological laboratory parameters: number of participants with abnomal laboratory values	Safety criterion	baseline, week 4, week 12, week 24, week 38 and week 52
Secondary	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

External Links

•   Results summary