Clinical Trials Register

Summary
EudraCT Number:	2006-004152-20
Sponsor's Protocol Code Number:	AVA102675
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:	2007-07-23
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

2006-004152-20

A.3

Full title of the trial

Estudio de extensión abierto de 52 semanas de la eficacia y la seguridad a largo plazo de rosiglitazona de liberación prolongada (RSG XR) como tratamiento complementario a los inhibidores de la acetilcolinesterasa en sujetos con enfermedad de Alzheimer leve o moderada (REFLECT-4).

A.4.1

Sponsor's protocol code number

AVA102675

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research & Development Ltd
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Rosiglitazone XR
D.3.2	Product code	BRL-049653
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	155141290
D.3.9.2	Current sponsor code	BRL-049653
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Rosiglitazone XR
D.3.2	Product code	BRL-049653
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	155141290
D.3.9.2	Current sponsor code	BRL-049653
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	4
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Rosigitazone XR
D.3.2	Product code	BRL-049653
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	155141290
D.3.9.2	Current sponsor code	BRL-049653
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	8
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Enfermedad de Alzheimer

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10001896
E.1.2	Term	Alzheimer's disease

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the long-term safety and tolerability of RSG XR in subjects with mild-to-moderate AD who have completed
either Study AVA102670 or AVA102672.
•El objetivo principal de este estudio es evaluar la seguridad y la tolerabilidad a largo plazo de RSG XR en sujetos con EA leve o moderada que hayan completado los estudios AVA102670 o AVA102672.

E.2.2

Secondary objectives of the trial

The secondary objective of this study is to explore further the long-term efficacy of
RSG XR on cognitive function and overall clinical response in subjects with mild tomoderate AD who have completed either Study AVA102670 or AVA102672.
•El objetivo secundario de este estudio es evaluar en mayor detalle la eficacia a largo plazo de RSG XR en la función cognitiva y la respuesta clínica global en sujetos con EA leve o moderada que hayan completado los estudios AVA102670 o AVA102672.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Sujetos de ambos sexos que hayan completado satisfactoriamente la visita 10 de los estudios AVA102670 o AVA102672 sin problemas de seguridad/tolerabilidad, los cuales, según la opinión del sujeto/cuidador, obtendrían un beneficio del tratamiento con RSG XR. Sin embargo, los sujetos que hayan completado la fase de tratamiento doble ciego podrán ser incluidos en el estudio si se retiran durante las últimas 6 semanas de los estudios AVA102670 o AVA102672 por cualquier motivo que no sea la seguridad (los sujetos que se retiren de los estudios AVA102670 o AVA102672 debido a problemas de seguridad/tolerabilidad durante las últimas 6 semanas de tratamiento no podrán ser incluidos en este estudio).
2. Las mujeres con capacidad para tener hijos deben aceptar utilizar un método de anticoncepción adecuado durante la totalidad del estudio (véase el Apéndice 11.1 para obtener detalles sobre los métodos de alta eficacia para evitar el embarazo). A las mujeres que sean premenopáusicas o posmenopáusicas desde hace menos de 1 año se las debe realizar una prueba de embarazo (en orina) ≤ 7 días antes de la visita 1, que debe ser negativa .
3. El sujeto está dispuesto a participar en el estudio de extensión y ha proporcionado su consentimiento informado por escrito antes de realizarse ningún procedimiento especificado en el protocolo o, si no es capaz de proporcionar el consentimiento informado debido a su estado cognitivo, su representante legal proporciona el consentimiento informado por escrito en nombre del paciente (de acuerdo con la legislación, normativa y política del comité ético de investigación clínica local).
4. El sujeto vive con (o tiene periodos considerables de contacto con) un cuidador habitual que está dispuesto a acudir a todas las visitas, supervisar el cumplimiento por parte del sujeto de la medicación del estudio y de los procedimientos especificados por el protocolo e informar sobre el estado del sujeto .
5. El sujeto puede realizar los procedimientos de evaluación cognitiva y de otro tipo.
6. El cuidador ha proporcionado su consentimiento informado pleno en nombre del sujeto por escrito antes de la realización de cualquier procedimiento especificado por el protocolo.
7. Los sujetos que están siendo considerados para la inclusión en el estudio deben tener un QTc (ya sea QTc B (corrección de Bazett) o QTc F (corrección de Fridericia)) < 450 ms en la visita 1, con la excepción de los sujetos con bloqueo de rama (para los cuales el QTc B o QTc F debe ser < 480ms) .
8. En Francia, un sujeto será elegible para participar en este estudio sólo si está afiliado o si es beneficiario de una categoría de la seguridad social.

E.4

Principal exclusion criteria

1. El sujeto ha experimentado un acontecimiento adverso grave o una anomalía de laboratorio clínicamente significativa durante los estudios AVA102670 o AVA102672 que, en opinión del investigador, podrían haber sido atribuibles a la medicación del estudio, y que persisten en la visita 1.
2. El investigador considera que el sujeto no es adecuado (en función de su salud, cumplimiento, disponibilidad de cuidador u otros motivos) para su inclusión en el estudio.
3. El sujeto experimentó un episodio cardiovascular importante durante los estudios AVA102670 o AVA102672 (p. ej., intervención, intervención coronaria percutánea, cirugía vascular, síndrome coronario agudo [infarto de miocardio sin onda Q, infarto de miocardio con onda Q, angina inestable] o arritmia significativa), a menos que se haya realizado una evaluación cardiovascular completa que confirme que el sujeto no tiene insuficiencia cardíaca congestiva y está clínicamente estable.
4. Datos clínicos o de laboratorio de insuficiencia cardíaca congestiva definida por los criterios de la New York Heart Association (estado cardíaco de clase I a IV) en el momento de la visita 1.
5. Edema periférico clínicamente importante en el momento de la visita 1.
6. Valores de alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) o fosfatasa alcalina > 2,5 veces el límite superior de la normalidad (LSN), valores de bilirrubina total > 1,5 veces el LSN o antecedentes de enfermedad hepatobiliar grave (p. ej., hepatitis B o C, o cirrosis, clase B/C de Child-Pugh).
Sólo en Canadá, se realizará el siguiente cambio al criterio de exclusión número 6. Valores de ALT, AST o fosfatasa alcalina > 2,0 veces el LSN, valores de bilirrubina total > 1,5 veces el LSN o antecedentes de enfermedad hepatobiliar grave (p. ej., hepatitis B o C, o cirrosis, clase B/C de Child-Pugh).
7. El sujeto es un familiar de primer grado o empleado del investigador participante, del personal del centro participante o de GSK.
8. En Francia, el sujeto no está afiliado ni es beneficiario de una categoría de seguridad social.
9. En Francia, el sujeto ha participado en cualquier estudio con un fármaco experimental durante los 30 días previos (excepto la participación en los estudios AVA102670 o AVA102672).

E.5 End points

E.5.1

Primary end point(s)

The primary safety endpoint is the incidence and severity of AEs.
El criterio principal de valoración de la seguridad es la incidencia y la gravedad de acontecimientos adversos (AA).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Information not present in EudraCT

E.6.2

Prophylaxis

Information not present in EudraCT

E.6.3

Therapy

Information not present in EudraCT

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Information not present in EudraCT

E.6.7

Pharmacodynamic

Information not present in EudraCT

E.6.8

Bioequivalence

Information not present in EudraCT

E.6.9

Dose response

Information not present in EudraCT

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

Information not present in EudraCT

E.6.12

Pharmacoeconomic

Information not present in EudraCT

E.6.13

Others

Information not present in EudraCT

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Extension study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.5

The trial involves multiple Member States

Information not present in EudraCT

E.8.5.1

Number of sites anticipated in the EEA

235

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

Information not present in EudraCT

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

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

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

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

Yes

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

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

1220

F.4.2.2

In the whole clinical trial

1500

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)

No se proporcionara tratamiento con RSG tras finalizar el estudio los pacientes recibiran el tratamiento estandar decidido por el medico investigador.

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

2007-09-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-08-06

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

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