Clinical Trials Register

Summary
EudraCT Number:	2011-005862-40
Sponsor's Protocol Code Number:	CL2-38093-012
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-06-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2011-005862-40

A.3

Full title of the trial

Efficacy and safety of 3 doses of S 38093 (2, 5 and 20 mg/day) versus placebo, in co-administration with donepezil (10 mg/day) in patients with moderate Alzheimer?s Disease.
A 24-week international, multi-centre, randomised, double-blind, placebo-controlled phase IIb study.

Eficacia y seguridad de 3 dosis de S38093 (2, 5 y 20 mg/dia)frente a placebo, asociado a donepezilo (10 mg/dia) en pacientes con enfermedad de Alzheimer moderada. Estudio de fase II b, internacional, multicéntrico, aleatorizado, doble ciego, controlado frente a placebo, de 24 semanas de duración

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and safety of S 38093 versus placebo, in co-administration with donepezil in patients with moderate Alzheimer's disease.

Evaluación de la eficacia y seguridad de S38093 frente a placebos, asociados ambos a donepezilo en pacientes con enfermedad de Alzheimer en estadío moderado

A.4.1

Sponsor's protocol code number

CL2-38093-012

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Laboratorios Servier S.L.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Laboratorios Servier S.L.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Laboratorios Servier S.L.
B.5.2	Functional name of contact point	Departamento I+D
B.5.3	Address:
B.5.3.1	Street Address	Avenida de los Madroños, 33
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28043
B.5.3.4	Country	Spain
B.5.4	Telephone number	34917489670
B.5.5	Fax number	34913003249
B.5.6	E-mail	maria.dequintana@es.netgrs.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	S38093
D.3.2	Product code	S38093-2
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S38093
D.3.9.2	Current sponsor code	S38093-2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	S38093
D.3.2	Product code	S38093-2
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S38093
D.3.9.2	Current sponsor code	S38093-2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	S38093
D.3.2	Product code	S38093-2
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S38093
D.3.9.2	Current sponsor code	S38093-2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ARICEPT
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratories Eisai
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	donepezil
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DONEPEZIL HYDROCHLORIDE
D.3.9.1	CAS number	120011-70-3
D.3.9.4	EV Substance Code	SUB13647MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

moderate Alzheimer's disease

Enfermedad de Alzheimer en estadío moderado

E.1.1.1

Medical condition in easily understood language

moderate Alzheimer's disease

Enfermedad de Alzheimer en estadío moderado

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10001896
E.1.2	Term	Alzheimer's disease
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of 3 fixed doses of
S 38093 (2, 5 and 20mg/ day) versus placebo, in co-administration with donepezil 10 mg/day, after 24 weeks of treatment, on cognitive performance measured with the ADAS-Cog 11-items in patients with moderate Alzheimers' Disease

Evaluar la eficacia de 3 dosis fijas de S38093 (2, 5, y 20 mg/dia) frente a placebo asociado a donepezilo (10 mg/día) en la función cognitiva mediante la escala ADAS-Cog de 11 puntos tras 24 semanas de tratamiento

E.2.2

Secondary objectives of the trial

Efficacy and safety

Evaluar la eficacia de 3 dosis de S38093 (2, 5 y 20 mg/dia) frente a placebo asociado a donepezilo (10 mg/dia) en la función cognitiva y síntomas neuropsiquiátricos mediante otras escalas : la DAD, MMSE, ADCS-CGI e inventario NPI tras 24 semanas de tratamiento y Evaluar la seguridad de S3809 frentea placebo asociado a donepezilo tras 24 semanas de tratamiento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Age 55-85 years (both inclusive)
-School education ? 4 years (i.e. formal schooling),
-DSM-IV-TR criteria for Dementia of the Alzheimer?s Type
. Memory impairment and
. One or more cognitive disturbances: Aphasia, apraxia, agnosia or disturbance in executive functioning.
. Significant impairment of social or occupational functioning due to cognitive deficits, with a decline from previous functioning,
. Gradual onset of disease and continuous cognitive decline,
. Deficit not due to delirium or any other medical cause.
-NINCDS-ADRDA criteria for probable AD
. Dementia established by clinical and confirmed by neuropsychological examination,
. Progressive cognitive impairment,
. Cognitive impairment in two or more areas of cognition,
. Absence of other diseases possibly inducing dementia.
-Total score of Mini-Mental State Examination (MMSE) between 12 and 20, both inclusive.
Modified Hachinski Scale ? 4,
-Geriatric Depression Rating Scale-15 (GDS) score ? 5
-Donepezil treatment (tablets of 5 or 10 mg/d) for at least 4 months before selection, and at a stable dose of 10 mg/day for at least 3 months before the selection visit.

Pacientes ambulatorios entre 55 y 85 años con un nivel de escolarización? 4años, con deterioro cognitivo (criterios DSM-IV-TR para el diagnóstico de demencia tipo Alzheimer y criterios NINCDS/ADRDA para el diagnóstico de probable EA) con una MMSE de entre 12-20, con una puntuación? 5 en la escala de depresión geriátrica y ? 4 para la escala de isquemia de Hachinski modificada que hayan estado tratados con donepezilo en los últimos 4 meses y con una dosis estable de 10 mg/dia en los últimos 3 meses. Deben tener además un cuidador responsable que conozca al paciente desde al menos 1 año y que esté en contacto con él un mínimo de 10 h/semana

E.4

Principal exclusion criteria

In-patients (e.g. hospitalised patients, institutionalised patients [patients in day care centers or in institutions where only meals and medications are provided, can be selected]),
- Patients not being able to read or write before onset of Alzheimer's Disease,
- Female patients of child-bearing potential (e.g., not menopausal for at least 2 years prior to selection or not having had hysterectomy),
- Dementia due to any condition other than AD
- History of epilepsy or solitary seizure (generalised or partial),
Schizophrenia, Schizoaffective Disorder, Bipolar Disorders,
- Major depressive disorder within the two months prior to inclusion. Patients with AD and associated stable depressive symptoms (stable for at least 2 months prior to inclusion) can be selected.

Pacientes ingresados (hospitalizados o ingresados en alguna institución) pacientes incapaces de leer o escribir, mujeres en edad fértil (no postmenopáusicas durante al menos los dos años previos a la visita de selección o sin histerectomia), ausencia del cuidador, demencia debida a cualquier otra enfermedad diferente a la enfermedad de Alzheimer, historia previa de epilepsia o convulsión aislada, e esquizofrenia, trastorno esquizoafectivo o trastorno bipolar, trastorno depresivo mayor en los dos meses previos a la inclusión. Pacientes con EA y síntomas depresivos estables asociados (estables durante al menos dos meses previos a la inclusión) si podrían seleccionarse

E.5 End points

E.5.1

Primary end point(s)

Alzheimer?s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) 11 items

Subescala Cognitiva de evaluación de la enfermedad de Alzheimer (ADAS-Cog) de 11 puntos

E.5.1.1

Timepoint(s) of evaluation of this end point

W0, W12 and W24

Visitas W0 (inclusión), W12 (semana 12 tras inclusión)y W24 (semana 24 trás inclusión)

E.5.2

Secondary end point(s)

Disability Assessment for Dementia (DAD)

Eficacia: Escala de Evaluación de la discapacidad en demencia (DAD), escala mental breve (MMSE), Escala de impresión clinica a cerca de los cambios generales (ADCS-CGIC), Inventario neuropsiquiátrico (NPI), Escala para medir la carga del cuidador (Zarit Burden Inventory). Seguridad: acontecimientos adversos, signos vitales, ECG, análisis de laboratoeio

E.5.2.1

Timepoint(s) of evaluation of this end point

W0 and W24

Criterios de eficacia en W0 (visita de inclusión), W12 (semana 12) y W24 (semana 24). Criterios de seguridad en todas las visitas del protocolo ASSE, W0, W4, W12, W24, WEND en los contactos teléfónicos se les preguntará a pacientes y cuidadores por posibles acontecimientos adversos que hayan podido tener

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

100

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Austria

Brazil

Canada

Finland

Germany

Italy

Mexico

Poland

Portugal

Slovakia

Spain

Sweden

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

última visita del último paciente incluido

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

900

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients with moderate Alzheimer's disease

Pacientes con enfermedad de Alzheimer en estadío moderado

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

750

F.4.2.2

In the whole clinical trial

1000

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The investigator will prescribe appropriate medication and/or arrange access to appropriate care for the patient.

El investigador prescribirá la medicación apropiada y/o se encargará de que el paciente reciba los cuidados apropiados

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-09-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-14

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials