Clinical Trials Register

Summary
EudraCT Number:	2011-005862-40
Sponsor's Protocol Code Number:	CL2-38093-012
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-03
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

Italy - Italian Medicines Agency

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.

Efficacia e sicurezza di 3 dosi di S38093 (2, 5 e 20 mg/die) verso placebo, in co-somministrazione con donepezil (10 mg/die) in pazienti con Malattia di Alzheimer di grado moderato. Studio di fase IIb, della durata di 24 settimane, multicentrico, internazionale, randomizzato, doppio ceco, placebo controllato.

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

Efficacia e sicurezza di S38093 verso placebo, in co-somministrazione con donepezil in pazienti con malattia di Alzheimer di grado moderato.

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	INSTITUT DE RECHERCHES INTERNATIONALES SERVIER
B.1.3.4	Country	Italy
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	ADIR
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ISTITUTO DI RICERCA SERVIER
B.5.2	Functional name of contact point	Project Manager - CHIARA PERTICA
B.5.3	Address:
B.5.3.1	Street Address	Via Luca Passi, 85
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00166
B.5.3.4	Country	Italy
B.5.4	Telephone number	06-669081
B.5.5	Fax number	06-66908738
B.5.6	E-mail	infoirs@it.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.3.9.2	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.3.9.2	Current sponsor code	S38093
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.3.9.2	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	Laboratoires 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.3.4	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

Malattia di Alzheimer di grado moderato

E.1.1.1

Medical condition in easily understood language

Moderate Alzheimer's disease

Malattia di Alzheimer di grado moderato

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	15.0
E.1.2	Level	HLT
E.1.2	Classification code	10001897
E.1.2	Term	Alzheimer's disease (incl subtypes)
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	SOC
E.1.2	Classification code	10029205
E.1.2	Term	Nervous system disorders
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

Valutare l’efficacia di 3 dosi prestabilite di S 38093 (2, 5 e 20 mg/die) verso placebo, in co–amministrazione con il donepezil 10 mg/die in pazienti con Alzheimer di grado moderato dopo un periodo di 24 settimane, sulle capacità cognitive valutate tramite la scala di valutazione ADAS-Cog ad 11 item.

E.2.2

Secondary objectives of the trial

Efficacy and Safety

Valutare l'efficacia e la sicurezza

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

Età compresa o uguale: 55-85 anni -Scolarità ≥ 4 anni -Criteri DSM-IV-TR per la demenza di tipo Alzheimer: *Deterioramento della memoria e uno o più dei seguenti disturbi cognitivi: Afasia, aprassia, agnosia o disturbo delle capacità funzionali esecutive, *Significativo deterioramento della funzionalità sociale o occupazionale a causa del deterioramento cognitivo, con un declino delle precedenti capacità funzionali,*Manifestazione graduale della patologia e declino cognitivo continuo, *Deficit non riconducibile a delirium o altre cause cliniche - Criteri del NINCDS-ADRDA per diagnosi di probabile malattia di Alzheimer.Demenza diagnosticata con esame clinico e confermata da valutazione neuropsicologica *Deterioramento cognitivo progressivo *Deterioramento cognitivo in due o più aree cognitive *Assenza di altre patologie che potrebbe potenzialmente portare alla demenza -Punteggio totale del Mini-Mental State Examination (MMSE) compreso tra 12 e 20(compresi) -Altri criteri: Punteggio della Scala di Hachinski modificata ≤ 4*Punteggio della Scala Geriatric Depression Rating -15 (GDS) ≤ 5. -Donepezil 10 mg per un periodo di almeno 4 mesi in cui il dosaggio deve essere stabile a 10 mg – negli ultimi 3 mesi prima della data di selezione

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.

-Pazienti ricoverati (in ospedale od in istituti di cura), tuttavia i pazienti ospitati in case di cura dove vengono assistiti solo per i pasti e la somministrazione delle medicine possono essere selezionati. -Pazienti incapaci a leggere o scrivere prima dell’insorgenza della malattia di Alzheimer. -Donne in età fertile (per esempio in menopausa da meno di 2 anni e non isterectomizzate) -Demenza dovuta a qualunque altra condizione che non sia la malattia di Alzheimer -storia di epilessia o episodio singolo di convulsioni, (generale o parziale) -Schizofrenia, Disturbo schizo-affettivo, Disturbo Bipolare -Depressione maggiore nei 2 mesi precedenti all’inclusione - pazienti affetti da Alzheimer con sintomi depressivi stabili associati (stabili da almeno 2 mesi prima dell'inclusione) possono essere selezionati.

E.5 End points

E.5.1

Primary end point(s)

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

ADAS-Cog: Scala di Valutazione dell’Alzheimer – sottoscala Cognitivo a 11 items

E.5.1.1

Timepoint(s) of evaluation of this end point

W0, W12 and W24

Alle settimane 0, 12 e 24

E.5.2

Secondary end point(s)

Disability Assessment for Dementia (DAD)

Valutazione della disabilità per demenza (DAD)

E.5.2.1

Timepoint(s) of evaluation of this end point

W0 and W24

Alla settimana 0 e 24

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

Brazil

Canada

Mexico

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

Last visit last subject

Ultima visita dell'ultimo soggetto

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

Number of subjects for this age range:

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

Pazienti con malattia di Alzheimer di grado moderato

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

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

Lo sperimentatore prescriverà la cura più appropriata e/o provvederà a far accedere il paziente alle cure più appropriate

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

2012-08-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-22

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