Clinical Trials Register

Summary
EudraCT Number:	2012-004763-45
Sponsor's Protocol Code Number:	14861A
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:	2014-01-10
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

Spain - AEMPS

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; study 1

Estudio aleatorizado, doble ciego, de grupos paralelos y controlado con placebo, de dosis fijas de Lu AE58054 en pacientes con enfermedad de Alzheimer leve o moderada tratados con donepezilo; estudio 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

Estudio de Lu AE58054 en pacientes con enfermedad de Alzheimer leve o moderada tratados con donepezilo.

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

Enfermedad de Alzheimer

E.1.1.1

Medical condition in easily understood language

Alzheimer?s disease

Enfermedad de 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	16.1
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

Establecer la eficacia de Lu AE58054 como tratamiento adyuvante del donepezilo para el tratamiento sintomático de los pacientes con enfermedad de Alzheimer leve o moderada

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

Investigar el efecto de Lu AE58054 como tratamiento adyuvante del donepezilo sobre los síntomas neuropsiquiátricos en pacientes con enfermedad de Alzheimer leve o moderada

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.

- El paciente tiene un cuidador informado y fiable.
- El paciente es un paciente ambulatorio.
- El paciente padece Enfermedad de Alzheimer EA probable.
- El paciente padece EA leve o moderada.
- Tratamiento estable con con donepezilo.
- El paciente, si es una mujer, debe haber tenido su última menstruacción natural como mínimo?24 antes de la visita de selección O haber sido esterilizadas quirurgicamente.
- El paciente, si es un hombre, está de acuerdo con utilizar los métodos anticonceptivos definidos en el protocolo si su pareja tiene capacidad de procrear O deben haber sido esterilizados quirurgicamente antes de la visita de selección.

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.

-El paciente presenta signos de enfermedad neurodegenerativa clínicamente significativa y otros trastornos neurológicos graves distintos de la EA.
- El paciente tiene un trastorno del eje I conforme al Manual diagnóstico y estadístico de los trastornos mentales, 4ª edición, texto revisado (DSM-IV-TR) distinto de la EA.
- El paciente tiene signos de una enfermedad clínicamente significativa.
-Es probable que se interrumpa o suspenda de forma definitiva el tratamiento con donepezilo del paciente durante el estudio.
- El paciente está recibiendo memantina o ha utilizado memantina en los 2 meses previos a la visita de selección.

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.

Cambio en la función cognitiva: Cambio en la puntuación total de la subescala cognitiva de la escala de evaluación de la Enfermedad de Alzheimer (ADAS-cog).

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and Week 24

Momento Basal y Semana 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)

- Cambio en la impresión global: Puntuación de la Escala de Impresión Clínica Global de Cambio del Estudio Cooperativo de la Enfermedad de Alzheimer (ADCS-CGIC).
- Cambio en función: Cambio en la puntuación total del Cuestionario sobre actividades de la vida diaria del Estudio Cooperativo de la Enfermedad de Alzheimer (ADCS-ADL23).
-Cambio en trastornos del comportamiento; cambio en la puntuación total del Inventario neuropsiquiátrico (NPI).
-Cambio en items individuales de trastorno del comportamiento; Cambio en la puntuación de ítems individuales del NPI.
-Cambio en la ansiedad;cambio en la puntuación del ítem del Inventario neuropsiquiátrico (NPI) basados en una puntuación pre especificada del la ansiedad NPI en el momento basal
-Respuesta clínica: Basada en cambios pre-especificados en ADAS-cog, ADCS-ADL23 y ADCS-CGIC.
- Empeoramiento clínico: Pasado en cambios pre-especificados en ADAS-Cog, ADACS-ADL23 y ADCS-CGIC.
- Cambio en aspectos cognitivos de la función mental: Cambio en el Miniexamen cognoscitvo (MMSE).
- Cambio en la calidad de vida relacionada con la salud: Cambio en la puntuación de utilidad del cuestionario EuroQoL 5-dimensional (EQ-5D)
-Cambio en la calidad de vida relacionada con la salud: Cambio en la Escala Analógica Visual (EQ-5D VAS)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline and Week 24

Momento Basal y Semana 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

Belgium

Bulgaria

Canada

Denmark

France

Italy

Sweden

Argentina

Chile

Czech Republic

Germany

Spain

Poland

South Africa

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

Última visita del último paciente

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.

Pacientes con Enfermedad de Alzheimer

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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.

Los pacientes que completen el período de tratamiento de 24 semanas podrán ser elegibles para participar en un estudio de extensión abierto de 6 meses con Lu AE58054 y donepezilo. Alternativamente los pacientes serán tratados de acuerdo a la práctica clínica habitual.

Para los pacientes que no entren en el estudio de extensión abierto, al periodo de tratamiento de 24 semanas le seguirá un periodo de seguimiento de seguridad de 4 semanas sin tratamiento con PEI.

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

2013-12-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-07-19

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