Clinical Trials Register

Summary
EudraCT Number:	2009-015713-51
Sponsor's Protocol Code Number:	205.452
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:	2010-03-24
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

Spain - AEMPS

A.2

EudraCT number

2009-015713-51

A.3

Full title of the trial

Ensayo clínico multicéntrico, aleatorizado, doble ciego, doble enmascarado controlado con principio activo y de grupos paralelos, para comparar la eficacia y seguridad de Tiotropio 2,5 µg y 5 µg solución para inhalación administrada mediante el inhalador Respimat® con Tiotropio 18 µg cápsulas para inhalación, administradas mediante HandiHaler®.

A.3.2

Name or abbreviated title of the trial where available

TIOSPIR

A.4.1

Sponsor's protocol code number

205.452

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	Boehringer Ingelheim España, S.A
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	Yes
D.2.1.1.1	Trade name	Spiriva Respimat 2.5 microgram, solution for inhalation
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim International GmbH
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Spiriva Respimat 2.5 microgram, solution for inhalation
D.3.2	Product code	Ba 679 BR
D.3.4	Pharmaceutical form	Inhalation vapour, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tiotropium bromide
D.3.9.1	CAS number	411207313
D.3.9.2	Current sponsor code	Ba 679 BR
D.3.9.3	Other descriptive name	TIOTROPIUM BROMIDE MONOHYDRATE
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.124
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	Spiriva Respimat 1.25 microgram, solution for inhalation
D.3.2	Product code	Ba 679 BR
D.3.4	Pharmaceutical form	Inhalation vapour, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tiotropium bromide
D.3.9.1	CAS number	411207313
D.3.9.2	Current sponsor code	Ba 679 BR
D.3.9.3	Other descriptive name	TIOTROPIUM BROMIDE MONOHYDRATE
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.562
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	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	Yes
D.2.1.1.1	Trade name	SPIRIVA 18 microgram, inhalation powder, hard capsule
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim International GmbH
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	SPIRIVA 18 microgram, inhalation powder, hard capsule
D.3.2	Product code	Ba 679 BR
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tiotropium bromide
D.3.9.1	CAS number	411207313
D.3.9.2	Current sponsor code	Ba 679 BR
D.3.9.3	Other descriptive name	TIOTROPIUM BROMIDE MONOHYDRATE
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	22.5
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)	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation vapour, solution
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Enfermedad Pulmonar Obstructiva Crónica (EPOC)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10009033
E.1.2	Term	<Manually entered code. Term in E.1.1>

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Comparar la eficacia y la seguridad de la solución para inhalación de tiotropio 2,5 µg y 5 µg administrada mediante el inhalador Respimat® con las cápsulas para inhalación de tiotropio 18 µg administradas mediante HandiHaler®.

E.2.2

Secondary objectives of the trial

-Número de exacerbaciones de la EPOC
-Tiempo hasta la primera hospitalización debido a exacerbación de la EPOC
-Número de hospitalizaciones debido a exacerbaciones de la EPOC
-Tiempo hasta el primer acontecimiento cardiovascular adverso importante

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Este estudio incluye la evaluación de la función pulmonar en una población total de 1305 pacientes reclutados de centros de determinados países.
La evaluación de la función pulmonar en esta subpoblación está descrita en el protocolo del estudio (de fecha 17 de febrero de 2010).

E.3

Principal inclusion criteria

1. Todos los pacientes deberán firmar un formulario de consentimiento informado de conformidad con las guías de BPC de la ICH antes de participar en el ensayo, lo que incluye cualquier período de lavado previo y las restricciones de medicación establecidas

2. Pacientes de ambos sexos de > 40 años.

3. Los pacientes deberán ser fumadores o ex fumadores con antecedentes de tabaquismo de > 10paquetes-año. (Se excluirán los pacientes que nunca hayan fumado cigarrillos).

4. Todos los pacientes deben presentar un diagnóstico de EPOC (P06-12085) y cumplir los siguientes criterios:
obstrucción de las vías respiratorias relativamente estable con un
FEV1 post-broncodilatador > 70% del valor normal teórico y un
FEV1/FVC post-broncodilatador > 70%.

5. Los pacientes deben ser capaces de inhalar de los dispositivos HandiHaler® y Respimat®.

E.4

Principal exclusion criteria

1. Enfermedades significativas aparte de la EPOC

2. Pacientes con antecedentes recientes (es decir, 6 meses o menos) de infarto de miocardio

3. Pacientes con arritmia cardíaca inestable o potencialmente mortal que haya requerido intervención o modificación del tratamiento farmacológico durante el último año.

4. Hospitalización por insuficiencia cardíaca (Clase III o IV de la New York Heart Association [NYHA]) durante el último año

5. Tuberculosis activa conocida.

6. Pacientes con antecedentes de asma, fibrosis quística, bronquiectasias, enfermedad pulmonar intersticial o enfermedad tromboembólica pulmonar.

7. Antecedentes de toracotomía con resección pulmonar

8. Pacientes que tengan previsto someterse a un trasplante de pulmón o a cirugía de reducción del volumen pulmonar (CRVP).

9. Neoplasia por la que el paciente se haya sometido a resección, radiación, quimioterapia o tratamientos biológicos en los últimos 5 años. Se aceptan los pacientes con carcinoma basocelular tratado.

10. Infección respiratoria o exacerbación de la EPOC en las cuatro semanas previas a la selección.

11. Hipersensibilidad conocida a los fármacos anticolinérgicos, la lactosa, el cloruro de benzalconio (BAC), el ácido etilendiaminotetraacético (EDTA) o cualquier otro componente del sistema de administración HandiHaler® o Respimat® solución para inhalación .

12. Pacientes con diagnóstico de insuficiencia renal moderada o grave (a criterio del investigador).

13. Pacientes con diagnóstico de glaucoma de ángulo cerrado.

14. Pacientes con hiperplasia prostática u obstrucción del cuello vesical sintomáticas significativas. Pueden incluirse los pacientes con síntomas controlados con tratamiento.

15. Uso de medicación con corticoesteroides sistémicos a dosis inestables.

16. Mujeres embarazadas o lactantes o en edad fértil que no estén utilizando métodos anticonceptivos médicamente probados.

17. Consumo significativo de alcohol o fármacos en los últimos 12 meses.

18. Pacientes que requieran el uso de oxigenoterapia suplementaria durante > 12 horas al día.
19. Pacientes que han finalizado un programa de rehabilitación pulmonar en las 6 semanas previas a la visita de selección o pacientes que actualmente están en un programa de rehabilitación pulmonar que no se mantendrá durante el estudio.

20. Pacientes que han tomado un producto en investigación en los 30 días previos a la visita de selección.

21. Participación previa (recepción de tratamiento aleatorizado) en este estudio

22. Pacientes que actualmente participan en un estudio intervencionista

E.5 End points

E.5.1

Primary end point(s)

El primer criterio principal de valoración es tiempo hasta la muerte por cualquier causa.
El segundo criterio principal de valoración es tiempo hasta la primera exacerbación de la EPOC.
Una exacerbación de la EPOC se define como un complejo de acontecimientos/síntomas de las vías respiratorias bajas (aumento o nueva aparición) relacionados con la EPOC subyacente, con duración de tres o más días y que requieren un cambio del tratamiento.

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

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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)

Yes

E.8.2.2

Placebo

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.8.4.1

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

650

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

El ensayo está basado en los acontecimientos tendrá un período de reclutamiento de 1,5 años y finalizará cuando se hayan notificado aproximadamente 1.266 acontecimientos adversos mortales. Se calcula que el ensayo durará aproximadamente 3,5 años.

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

330

F.4.2

For a multinational trial

F.4.2.1

In the EEA

6340

F.4.2.2

In the whole clinical trial

16800

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)

Normal treatment

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

2010-05-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-05-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-05-23

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