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

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.

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: S47445 5mg; Drug: S47445 15mg; Drug: S47445 50mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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).
Experimental: S47445 15mg	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).
Experimental: S47445 50mg	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).
Experimental: S47445 5mg	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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier

Publications and helpful links

Helpful Links

• Results summary

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: December 7, 2015
• First Posted (Estimate): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Depression; Alzheimer Disease
• Other Study ID Numbers: CL2-47445-011; 2014-001519-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

• submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR