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

NCT ID: NCT02626572

Last Updated: 2024-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2017-09-30

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

S47445 5mg

Group Type: EXPERIMENTAL

S47445 5mg

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

S47445 15mg

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

S47445 50mg

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

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).

Intervention Type: DRUG

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

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Trial Tech Tecnologia em Pesquisa com Medicamentos

Curitiba, , Brazil

Hospital Universitario Walter Cantidio

Fortaleza, , Brazil

Clinilive - Centro de Pesquisas Clinicas

Maringá, , Brazil

Hospital das Clinicas de Porto Alegre

Porto Alegre, , Brazil

Hospital Oswaldo Cruz

Recife, , Brazil

Instituto Américo Bairral de Psiquiatria, Centro de Pesquisa

São Paulo, , Brazil

UNIFESP - Universidade Federal de Sao Paulo

São Paulo, , Brazil

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, , Bulgaria

Clínica Oriente

Antofagasta, , Chile

Biomedica Research Group

Santiago, , Chile

Especialidades Medicas LYS

Santiago, , Chile

Hospital Santiago Oriente

Santiago, , Chile

Private practice

Santiago, , Chile

Saint Anne s.r.o. Psychiatricka ambulance

Brno, , Czechia

Brain-Soultherapy s.r.o.

Kladno, , Czechia

Bialbi s.r.o.

Litoměřice, , Czechia

AD71 s.r.o. Psychiatricka ambulance - Sudkova

Prague, , Czechia

CLINTRIAL s.r.o.

Prague, , Czechia

FORBELI s.r.o., Neurologicka ambulance

Prague, , Czechia

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, , Germany

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

Győr, , 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

Nyíregyháza, , Hungary

Pecsi Tudomanyegyetem, Klinikai Kozpont Pszich. es Pszichoter. Klinika

Pécs, , Hungary

Szent-Gyorgyi Albert Klinikai Kozpont Pszichiatriai Klinika

Szeged, , Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Pszichiatriai Osztaly

Székesfehérvár, , Hungary

Memory Clinic Ochanomizu

Bunkyō City, , Japan

Showakai Clinic

Kagoshima, , Japan

Rainbow & Sea Hospital

Karatsu-shi, , Japan

Kokan Clinic

Kawasaki-shi, , Japan

Social Medical Corporation Kojunkai Daido Hospital

Nagoya, , Japan

Nakano General Hospital

Nakano, , Japan

Private practice

Saitama-shi, , Japan

Private practice

Setagaya-ku, , Japan

Seishinkai Okehazama Hospital

Toyoake-shi, , Japan

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, , Mexico

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

SENIOR Poradnia Psychogeriatryczna

Sopot, , Poland

Osrodek Alzheimerowski Sp. z o.o.

Ścinawa, , Poland

Centrum Medyczne Neuroprotect

Warsaw, , Poland

Interregional Clinico-Diagnostical Centre

Kazan', , Russia

First Moscow State Medical University n.a.I.M. Sechenov Clinic of Neurology

Moscow, , Russia

Scientific Center of Mental Health Sect of AD and associated disord. Dpt of gerontopsychiatry

Moscow, , Russia

Scientific Center of Mental Health Sect of psychosis of elderly ages Dpt of gerontopsychiatry

Moscow, , Russia

City geriatric medico-social centre

Saint Petersburg, , Russia

Medical Military Academy n.a.S.M.Kirov

Saint Petersburg, , Russia

Psychoneuropathology Dispensary N 10

Saint Petersburg, , Russia

Co Ltd "LION-MED"

Voronezh, , Russia

Private practice

Bratislava, , Slovakia

INVESTA, spol. s r. o. Psychiatricka ambulancia

Košice, , Slovakia

NsP Svatej Barbory Psychiatricke oddelenie

Rožňava, , Slovakia

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, , South Africa

Countries

Brazil; Bulgaria; Chile; Czechia; Germany; Hungary; Japan; Mexico; Poland; Russia; Slovakia; South Africa

References

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.

Reference Type: RESULT

PMID: 31297437 (View on PubMed)

Other Identifiers

2014-001519-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL2-47445-011

Identifier Type: -

Identifier Source: org_study_id