Clinical Trials Register

Summary
EudraCT Number:	2012-004763-45
Sponsor's Protocol Code Number:	14861A
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:	2013-07-31
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-004763-45

A.3

Full title of the trial

Randomised, double-blind, parallel-group, placebo-controlled, fixed-dose study of Lu AE58054 in patients with mild-moderate Alzheimer’s disease treated with donepezil

Studio randomizzato, in doppio cieco, a gruppi paralleli, controllato con placebo, a dose fissa di LuAE58054, in pazienti affetti da malattia di Alzheimer da lieve a moderata, trattata con donepezil; studio 1

A.3.1

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

Study of Lu AE58054 in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil

“Studio su LuAE58054, in pazienti affetti da malattia di Alzheimer da lieve a moderata, trattata con donepezil”

A.4.1

Sponsor's protocol code number

14861A

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	H. Lundbeck A/S
B.1.3.4	Country	Denmark
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	H. Lundbeck A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	H. Lundbeck A/S
B.5.2	Functional name of contact point	lundbeckclinicaltrials@lundbeck.com
B.5.3	Address:
B.5.3.1	Street Address	Ottiliavej 9
B.5.3.2	Town/ city	Valby, Copenhagen
B.5.3.3	Post code	2500
B.5.3.4	Country	Denmark
B.5.6	E-mail	lundbeckclinicaltrials@lundbeck.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.3.2	Product code	Lu AE58054
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	Not available
D.3.9.2	Current sponsor code	Lu AE58054
D.3.9.4	EV Substance Code	SUB114522
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	30
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.3.2	Product code	Lu AE58054
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	Not available
D.3.9.2	Current sponsor code	Lu AE58054
D.3.9.4	EV Substance Code	SUB114522
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	60
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	Capsule
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

Alzheimer’s disease

Malattia di Alzheimer

E.1.1.1

Medical condition in easily understood language

Alzheimer’s disease

Malattia di Alzheimer

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	100000004852

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 establish efficacy of Lu AE58054 as adjunctive therapy to donepezil for symptomatic treatment of patients with mild-moderate Alzheimer’s disease

Stabilire l'efficacia di Lu AE58054 come terapia aggiuntiva a donepezil per il trattamento sintomatico di pazienti affetti da malattia di Alzheimer da lieve a moderata.

E.2.2

Secondary objectives of the trial

To investigate the effect of Lu AE58054 as adjunctive therapy to donepezil on neuropsychiatric symptoms in patients with mild-moderate Alzheimer’s disease

Valutare l'effetto che Lu AE58054, come terapia aggiuntiva a donepezil, produce sui sintomi neuropsichiatrici in pazienti affetti da malattia di Alzheimer da lieve a moderata.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• The patient has a knowledgeable and reliable caregiver.
• The patient is an outpatient.
• The patient has probable AD.
• The patient has mild to moderate AD.
• Stable treatment with donepezil.
• The patient, if a woman, must have had her last natural menstruation ≥24 months prior to baseline, OR be surgically sterile.
• The patient, if a man, agrees to protocol-defined use of effective
contraception if his female partner is of childbearing potential, OR must have been surgically sterilised prior to the screening visit.

• Il paziente ha una persona che presta le cure esperta e affidabile.
• Il paziente è un paziente ambulatoriale.
• Il paziente ha una diagnosi di probabile malattia di Alzheimer.
• Il paziente è affetto da malattia di Alzheimer da lieve a moderata.
• Il paziente è iin trattamento stabile con donepezil.
• Il paziente di sesso femminile deve aver avuto l'ultimo ciclo mestruale naturale almeno ≥24 mesi prima del baseline, o deve essere stato sottoposto a sterilizzazione chirurgica.
• I pazienti di sesso maschile acconsentono ad utilizzare un metodo contraccettivo efficace come definito da protocollo, se la compagna è potenzialmente fertile OPPURE devono essere stati sottoposti a sterilizzazione chirurgica prima della visita di screening.

E.4

Principal exclusion criteria

• The patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD.
• The patient has a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) Axis I disorder other than AD.
• The patient has evidence of clinically significant disease.
• The patient's donepezil therapy is likely to be interrupted or discontinued during the study.
• The patient is currently receiving memantine or has taken memantine within 2 months prior to screening.

• Il paziente mostra evidenza di qualsiasi malattia neurodegenerativa clinicamente significativa o di altri disturbi neurologici gravi diversi dalla malattia di Alzheimer.
• Il paziente soffre di un disturbo dell'asse I secondo il DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision, Manuale diagnostico e statistico dei disturbi mentali, quarta edizione, revisione del testo) diverso dalla malattia di Alzheimer.
• Il paziente mostra evidenza di una malattia clinicamente significativa
• È probabile che la terapia a base di donepezil del paziente venga interrotta o sospesa durante lo studio.
• Il paziente è trattato attualmente con memantina o ha assunto memantina nei 2 mesi precedenti alla visita di screening.

E.5 End points

E.5.1

Primary end point(s)

Change in cognition: Change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score.

Variazione facoltà cognitive: variazione del punteggio totale ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale, Sottoscala cognitiva della scala per la valutazione della malattia di Alzheimer)

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and Week 24

basale e settimana 24

E.5.2

Secondary end point(s)

• Change in global impression: Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score
• Change in functioning: Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score
• Change in behavioural disturbance: Change in Neuropsychiatric Inventory (NPI) total score
• Change in individual behavioural disturbance items: Change in single NPI item scores
• Change in anxiety: Change in NPI Anxiety item score based on a pre-specified NPI Anxiety score at Baseline
• Clinical response: Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes
• Clinical worsening: Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes
• Change in cognitive aspects of mental function: Change in Mini Mental State Examination (MMSE)
• Change in health-related quality of life: Change in EuroQol 5-dimensional (EQ-5D) utility score
• Change in health-related quality of life: Change in EQ-5D Visual Analogue Scale (EQ-5D VAS)

Punteggio ADCS-CGIC (Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change, Studio cooperativo sulla malattia di Alzheimer - Impressione globale del medico sul cambiamento)
 Variazione Funzionalità: punteggio totale ADCS-ADL23 (Alzheimer’s disease Cooperative Study - Activities of Daily Living Inventory, Studio cooperativo sulla malattia di Alzheimer - inventario delle attività della vita quotidiana)
 Variazione nel disturbo comportamentale: punteggio totale NPI (Neuropsychiatric Inventory, Inventario neuropsichiatrico)
 Variazione nel disturbo comportamentale: variazione delle singole voci dell'NPI
 Variazione dell’ansia: variazione rispetto al basale nel punteggio delle voci relative all’ansia dell’NPI
 Risposta clinica: variazioni pre-specificate del punteggio ADAS-cog, ADCS-ADL23 e ADCS-CGIC<=4)
 Peggioramento clinico: variazioni pre-specificate del punteggio ADAS-cog, ADCS-ADL23 e ADCS-CGIC
 Variazione degli aspetti cognitivi della funzione mentale: variazione del punteggio MMSE (Mini Mental State Examination, Mini esame dello stato mentale)
 Variazione della qualità della vita in connessione alla salute: variazione del punteggio di utilità dell'EQ-5D
 Variazione della qualità della vita in connessione alla salute: variazione della VAS (Visual Analogic Scale, Scala analogica visiva) dell'ED-5D

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline and Week 24

basale e settimana 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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

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

Belgium

Bulgaria

Canada

Chile

Czech Republic

Denmark

France

Germany

Italy

Poland

South Africa

Spain

Sweden

Ukraine

United States

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

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:

140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

790

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

Subjects with Alzheimer’s disease.

Soggetti affetti da malattia di
Alzheimer

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

407

F.4.2.2

In the whole clinical trial

930

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)

Patients completing the 24 week Treatment Period may be eligible to enter a 6-month open-label extension study with Lu AE58054 and donepezil. Alternatively the patient will be treated according to normal clinical practice.
For patients who do not enter the open-label extension study, the 24-week treatment period is followed by a 4-week safety follow-up period without treatment with IMP.

I pazienti che hanno completato il periodo di trattamento di 24 settimane possono essere ammessi a entrare in un studio di estensione in aperto di 6 mesi con Lu AE58054 e donepezil. Alternativamente il paziente sarà trattato secondo normale pratica clinica.
Per i pazienti che non entrano nello studio di estensione in aperto, il periodo di trattamento dfi 24 settimane è seguito da una visita di sicurezza, follow-up a 4 settimane senza trattamento con IMP.

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

2013-10-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-17

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

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