Clinical Trials Register

Summary
EudraCT Number:	2005-002256-17
Sponsor's Protocol Code Number:	178-CL-044
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:	2005-12-21
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

2005-002256-17

A.3

Full title of the trial

Estudio aleatorizado, doble ciego, multicéntrico, de grupos paralelos, controlado con placebo y con tratamiento activo, de búsqueda de dosis del agonista Beta-3 YM-178 en pacientes con Vejiga Hiperactiva (DRAGON)

A.3.2

Name or abbreviated title of the trial where available

DRAGON

A.4.1

Sponsor's protocol code number

178-CL-044

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	Astellas Pharma Europe B.V.
B.1.3.4	Country	Netherlands
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	Information not present in EudraCT
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	YM 178
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.3.9.2	Current sponsor code	YM178
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	25 to 200
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	producto de origen químico
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Information not present in EudraCT
D.2.1.1.1	Trade name	Detrusitol Neo
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	tolterodina
D.3.4	Pharmaceutical form	Prolonged-release capsule, hard
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.3.8	INN - Proposed INN	tartrato de tolterodina
D.3.9.1	CAS number	124937-52-6
D.3.9.3	Other descriptive name	Detrusitol Neo
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	Producto de origen químico

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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
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

Vejiga hiperactiva

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluar la relación dosis-respuesta sobre la eficacia de YM-178 OCAS en pacientes con vejiga hiperactiva.

E.2.2

Secondary objectives of the trial

- Evaluar la seguridad y tolerabilidad de la dosificación una vez al día de YM-178 OCAS en pacientes con vejiga hiperactiva.
- Comparar la eficacia de YM-178 OCAS frente a tolterodina 4 mg qd.
- Comparar la seguridad y tolerabilidad de YM-178 OCAS frente a tolterodina 4 mg qd.
- Recoger datos farmacocinéticos de la población de pacientes con VH.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

1. Varón o mujer con una edad ≥18 años.
2. Se ha obtenido el consentimiento informado por escrito.
3. El paciente es capaz y está dispuesto a completar correctamente el diario miccional y los cuestionarios.
4. Síntomas de vejiga hiperactiva (urgencia y frecuencia urinaria, con o sin incontinencia) durante ≥3 meses.

En el momento de la aleatorización:
5. El paciente debe presentar una frecuencia miccional media ≥8 veces cada 24 horas durante el periodo de 3 días de registro del diario miccional.
6. El paciente debe presentar al menos 3 episodios de urgencia con o sin incontinencia (grado 3 o 4), durante el periodo de 3 días de registro del diario miccional.

E.4

Principal exclusion criteria

A la entrada en el estudio:
1. Mujeres embarazadas; o mujeres que quieran quedarse embarazadas durante el estudio; o mujeres en edad fértil, sexualmente activas y que utilicen un método anticonceptivo poco fiable; o mujeres en periodo de lactancia durante el estudio. Los métodos anticonceptivos fiables son los dispositivos intrauterinos, las píldoras anticonceptivas de tipo combinación, los implantes hormonales, los parches anticonceptivos y los anticonceptivos inyectables.
2. Obstrucción al flujo urinario clínicamente significativa (a criterio del investigador).
3. Residuo postmiccional significativo (RP>200 ml).
4. Incontinencia de esfuerzo significativa o incontinencia mixta (esfuerzo/urgencia) en la que el esfuerzo es el factor predominante, según determine el investigador (en el caso de las mujeres, confirmado mediante una prueba de provocación por tos).
5. Pacientes con catéteres o que requieren cateterización intermitente.
6. Neuropatía diabética.
7. Evidencia de infección sintomática del tracto urinario, inflamación crónica como la cistitis intersticial, cálculos vesicales, radioterapia pélvica previa o patología maligna previa o actual de los órganos pélvicos.
8. Glaucoma de ángulo estrecho no controlado, retención urinaria o gástrica, colitis ulcerosa, megacolon tóxico, miastenia gravis o cualquier otra enfermedad que en opinión del investigador contraindique la utilización de anticolinérgicos.
9. Tratamiento no farmacológico incluyendo terapia de electroestimulación(un programa de entrenamiento vesical o ejercicios del suelo pélvico que comenzasen más de 1 mes antes del inicio del estudio pueden seguir utilizándose).
10. Utilización de fármacos para el tratamiento de la incontinencia urinaria o presentes en la lista del Apéndice 1, Parte A. La Parte B enumera una lista de fármacos restringidos pero que pueden aceptarse en determinadas condiciones.
11. Hipersensibilidad conocida o sospechada a tolterodina, otros anticolinérgicos, agonistas de los receptores ß-adrenérgicos, lactosa o cualquier otro de los excipientes inactivos.
12. Enfermedades cardiovasculares o cerebrovasculares clínicamente significativas en los 6 meses previos a la visita 1, como pueden ser infarto miocárdico, angina no controlada, arritmias ventriculares significativas, taquicardia sinusal, insuficiencia cardiaca (clase III/IV de la New York Heart Association), hipotensión ortostática, ictus e hipertensión no controlada, definida como una presión sistólica ≥180 mmHg y/o presión diastólica ≥110 mmHg determinada con el paciente sentado.
13. Cualquier enfermedad clínicamente significativa que, en opinión del investigador, incapacite al paciente para participar en el estudio.
14. Participación en cualquier estudio clínico en los 30 días (90 en el Reino Unido) previos a la aleatorización.
15. Empleados del grupo Astellas, terceras partes asociadas al estudio o al centro del estudio.
En el momento de la aleatorización:
16. Paciente que no completó el diario miccinal según las instrucciones.
17. Volumen miccional diario total medio >3.000 ml, según los registros recogidos en el diario miccional.
18. Elevación clínicamente significativa de la creatinina sérica o de las enzimas hepáticas, determinada como creatinina >150 mmol/L, AST o ALT más de dos veces por encima del límite superior de normalidad (LSN), gamma-GT más de 3 veces por encima del LSN y/o alteración de la bilirrubina total sérica (valorado en función de las muestras de la visita 1 o alternativamente muestras tomadas en las 4 semanas previas a la visita 1).
19. Un ECG alterado clínicamente significativo que, en opinión del investigador, incapacite al paciente para participar en el estudio.

E.5 End points

E.5.1

Primary end point(s)

Variable principal

Cambio respecto al basal en el número medio de micciones/24 h

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Information not present in EudraCT

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.8.3

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.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

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

Finalización normal del estudio:
- El paciente ha completado todas las visitas

El paciente termino prematuramente el estudio debido a alguna de las razones siguientes:
- Acontecimientos adversos
- Muerte del paciente
- Violaciones de protocolo
- Paciente perdido para seguimiento
- Falta de eficacia
- Retirada del consentimiento
- Otra

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	70
F.4.2	For a multinational trial
F.4.2.1	In the EEA	600
F.4.2.2	In the whole clinical trial	1070

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

2006-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-01-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2007-03-26

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