Clinical Trials Register

Summary
EudraCT Number:	2006-006796-21
Sponsor's Protocol Code Number:	D5892C00015
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:	2007-04-11
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

2006-006796-21

A.3

Full title of the trial

Ensayo de 12 semanas doble ciego, aleatorizado, de grupos paralelos y multicéntrico para evaluar la eficacia y la seguridad de budesonida/formoterol (Symbicort® Turbuhaler®) 320/9 µg, una inhalación dos veces al día, además de tiotropio (Spiriva®) 18 µg, una inhalación una vez al día, en comparación con tiotropio 18 μg, una inhalación una vez al día, en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) grave

A.3.2

Name or abbreviated title of the trial where available

CLIMB

A.4.1

Sponsor's protocol code number

D5892C00015

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

N/A

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	Symbicort Turbuhaler 320/9 microgram/inhalation
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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.3.4	Pharmaceutical form	Inhalation powder
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	Budesonida
D.3.9.1	CAS number	51333223
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	320
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	formoterol fumarato
D.3.9.1	CAS number	43229807
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	9
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	Yes
D.2.1.1.1	Trade name	Spiriva
D.2.1.1.2	Name of the Marketing Authorisation holder	Boehringer Ingelheim
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.3.4	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.3.9.1	CAS number	411207313
D.3.9.3	Other descriptive name	bromuro de tiotropio
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.IMP: 3
D.1.2 and D.1.3	IMP Role
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	Bricanyl Turbuhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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.3.4	Pharmaceutical form	Inhalation powder
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	Sulfato de terbutalina
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	500
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 powder
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) grave

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	10010952
E.1.2	Term	COPD

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

El objetivo principal de este ensayo es evaluar la eficacia en la función pulmonar de Spiriva®, 18 μg una inhalación una vez al día + Symbicort® Turbuhaler® 320/9 μg una inhalación dos veces al día, en comparación con Spiriva 18 μg una inhalación una vez al día en monoterapia.

E.2.2

Secondary objectives of the trial

El objetivo secundario del ensayo es evaluar la seguridad valorando la naturaleza, la incidencia y la intensidad de los AA y las constantes vitales en los grupos de tratamiento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Entrega del consentimiento informado antes de realizar cualquier procedimiento relacionado con el ensayo.
2. Pacientes ambulatorios de ambos sexos, de edad ³40 años
3. Diagnóstico clínico de EPOC y síntomas desde hace más de 2 años
4. Fumador o ex fumador, con antecedentes de tabaquismo equivalentes a 10 o más paquetes-años (1 paquetes-año = 20 cigarrillos al día durante un año)
5. Antecedentes de una exacerbación de la EPOC como mínimo, que precisara una dosis de esteroides orales o de antibióticos, entre 1 y 12 meses antes de la visita 2
6. FEV1 ≤50% del valor normal previsto, medido antes de administrar el broncodilatador
7. FEV1/VC <70%, antes de administrar el broncodilatador
8. Pacientes que sepan leer y escribir y utilizar los dispositivos electrónicos (diario-e y medidor de flujo máximo)
Para ser aleatorizados al período de tratamiento, deberán cumplirse los criterios siguientes en la visita 3:
9. Puntuación total de síntomas de la EPOC ≥2 al día durante al menos 7 días del período de preinclusión (suma de la puntuación de los apartados del diario: respiración, tos y opresión torácica) o durante al menos la mitad del período de preinclusión si duró más de 14 días
10. Registros matutinos de los datos de PEF y GCSQ al menos 7 de los últimos 10 días del período de preinclusión

E.4

Principal exclusion criteria

1. Empeoramiento de la EPOC durante la preinclusión o en las 4 semanas anteriores a la visita 2, que precise hospitalización, un ciclo de esteroides orales o inhalados, antibióticos o ambos
2. Uso de glucocorticosteroides inhalados en las 2 semanas anteriores a la visita 2
3. Uso de glucocorticosteroides orales/parenterales en las 4 semanas anteriores a la visita 2
4. Cualquier hallazgo anómalo de importancia clínica en la exploración física o las constantes vitales que, en opinión del investigador, pueda suponer un riesgo para el paciente a causa de su participación en el ensayo.
5. Antecedentes de asma
6. Antecedentes de rinitis alérgica estacional antes de los 40 años de edad
7. Cardiopatía isquémica importante o inestable, arritmia, miocardiopatía, insuficiencia cardíaca, insuficiencia renal, hipertensión no controlada en opinión del investigador o cualquier otro trastorno cardiovascular importante en opinión del investigador
8. Oxigenoterapia regular
9. Cualquier trastorno respiratorio activo distinto de la EPOC, que el investigador considere de importancia clínica
10. Cualquier enfermedad o trastorno importante que, en opinión del investigador, pueda poner al paciente en riesgo debido a su participación en el ensayo o influir en los resultados del ensayo o en la capacidad del paciente para participar en el mismo.
11. Pacientes con glaucoma de ángulo estrecho de importancia clínica, hiperplasia prostática importante u obstrucción del cuello de la vejiga en quienes el tratamiento con tiotropio pueda suponer un empeoramiento de los signos y síntomas relacionados con estas afecciones, a juicio del investigador
12. Pacientes en tratamiento con betabloqueantes no cardioselectivos
13. Embarazo, lactancia materna o embarazo previsto durante el ensayo. Mujeres fértiles que no utilicen medidas anticonceptivas aceptables, a juicio del investigador.
14. Hipersensibilidad presunta o confirmada al tratamiento del ensayo o a sus excipientes, incluida la atropina o sus derivados, y al ipatropio y sus componentes, a juicio del investigador
15. Hospitalización prevista del paciente durante el ensayo
16. Pacientes que hayan participado en un ensayo clínico para evaluar un fármaco en investigación en las 4 semanas anteriores al reclutamiento o a quienes se haya asignado previamente un código de aleatorización en este ensayo
17. Pacientes con antecedentes de alcoholismo o toxicomanía crónicos o con cualquier afección que se asocie a un cumplimiento insuficiente
18. Pacientes que estén participando o estén citados para participar en un programa intensivo de rehabilitación de la EPOC
19. Previsión de donar sangre durante el ensayo
20. Participación en la planificación y realización del ensayo (se aplica al personal tanto de AstraZeneca como del centro de ensayo)

E.5 End points

E.5.1

Primary end point(s)

La variable principal de valoración será la variación del FEV1 antes de la dosis entre el valor de la visita 3 y la media de los valores obtenidos entre las visitas 4 y 6. Esta variable se utilizó como base para el cálculo del tamaño de la muestra

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

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

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

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 final del ensayo se define como la fecha de cierre de la base de datos, que es el momento a partir del cual ningún paciente estará expuesto a actividades relacionadas con el ensayo.

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 months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
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	30
F.4.2	For a multinational trial
F.4.2.1	In the EEA	485
F.4.2.2	In the whole clinical trial	620

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

2007-05-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-05-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2008-06-16

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