Clinical Trials Register

Summary
EudraCT Number:	2011-000229-63
Sponsor's Protocol Code Number:	CQVA149A2322
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:	2011-06-29
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

2011-000229-63

A.3

Full title of the trial

Estudio cruzado de 3 periodos, multicéntrico, aleatorizado, ciego, doble enmascaramiento, y controlado con placebo para evaluar el efecto de QVA149 sobre la disnea notificada por el paciente en la enfermedad pulmonar obstructiva crónica (EPOC) de moderada a grave, utilizando tiotropio como control activo.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

evaluar el efecto de QVA149 sobre la disnea notificada por el paciente en la enfermedad pulmonar obstructiva crónica (EPOC) de moderada a grave, utilizando tiotropio como control activo.

A.4.1

Sponsor's protocol code number

CQVA149A2322

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	Novartis Farmacéutica S.A.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Farmacéutica S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmacéutica S.A.
B.5.2	Functional name of contact point	LARA BRIONGOS
B.5.3	Address:
B.5.3.1	Street Address	C/ Gran Via de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34 610 488 268
B.5.5	Fax number	+34 93 306 42 90
B.5.6	E-mail	lara.briongos@novartis.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	QVA149
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	NVA237
D.3.9.3	Other descriptive name	GLYCOPYRRONIUM BROMIDE
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	753498-25-8
D.3.9.2	Current sponsor code	QAB149
D.3.9.3	Other descriptive name	INDACATEROL MALEATE
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	110
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	Yes
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	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 microgramos, polvo para inhalación
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	Germany
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	No
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	TIOTROPIO BROMURO
D.3.9.3	Other descriptive name	TIOTROPIUM BROMIDE
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	18
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	Yes
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	Inhalation powder, hard capsule
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

E.1.1.1

Medical condition in easily understood language

Enfermedad Pulmonar

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demostrar que QVA149 110/50 µg q.d. es superior a placebo en términos de mejoría de la disnea notificada por el paciente evaluada mediante BDI/TDI (versión SAC) tras 6 semanas de tratamiento.

E.2.2

Secondary objectives of the trial

Demostrar que QVA149 110/50 µg q.d. es superior a tiotropio 18 µg q.d. en términos de mejoría de la disnea notificada por el paciente evaluada mediante elBDI/TDI (versión SAC) tras 6 semanas de tratamiento.
Evaluar QVA149 110/50 µg q.d. en comparación con placebo y tiotropio 18 µg q.d. tras 6 semanas de tratamiento en términos de;
FEV1 AUC 0-4 hrs estandarizado
FVC AUC 0-4 hrs estandarizado
El cambio medio desde la basal en las actividades de la mañana utilizando el Cuestionario de Capacidad de la Vida Diaria durante la Mañana (CDLM)
El cambio medio desde la basal en número de inhalaciones de medicación de rescate
Seguridad y tolerabilidad (acontecimientos adversos, analíticas de laboratorio, ECGs, y constantes vitales)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Hombre o mujer adultos con edad 40 años, que hayan firmado un Formulario de Consentimiento Informado antes de iniciar cualquier procedimiento relacionado con el estudio.
2. Pacientes con EPOC estable de moderada a grave (Estadio II o Estadio III) según las Normas GOLD 2009.
3. Fumadores o ex-fumadores con antecedentes de consumo de tabaco de al menos 10 paquetes años. (Diez paquetes-años se define como 20 cigarrillos al día durante 10 años, o 10 cigarrillos al día durante 20 años, etc.)
4. Pacientes con un FEV1 post-broncodilatación 30% y < 80% del valor teórico normal, y FEV1/FVC post-broncodilatación < 0,7 en la Visita 2 (Día -14).
(Post se refiere a 1 hora después de la inhalación secuencial de 84 µg (o dosis equivalente) de bromuro de ipratropio y 400 µg de salbutamol)
5. Grado mMRC de al menos 2 en la Visita 2.
6. Pacientes con capacidad para utilizar el ratón del ordenador y navegar por el monitor del ordenador.

E.4

Principal exclusion criteria

1. Mujeres embarazadas o madres en periodo de lactancia (embarazo confirmado por una prueba de embarazo en orina positiva).
2. Mujeres en edad fértil, definidas como toda mujer fisiológicamente capaz de quedarse embarazada, deben utilizar un método anticonceptivo efectivo durante el estudio. A MENOS que cumplan la siguiente definición de post-menopausia: 12 meses de amenorrea natural (espontánea) O que hayan pasado 6 semanas desde ooforectomía quirúrgica bilateral (con o sin histerectomía).
3. Pacientes con condiciones contraindicadas para el tratamiento con, o con antecedentes de reacciones/hipersensibilidad a alguno de los siguientes fármacos inhalados, fármacos de una clase similar o cualquier otro componente resultante
anticolinérgicos (e.g.,
beta-2 agonistas de larga y corta duración
aminas simpatitomiméticas
lactosa o cualquier otro excipiente.
4. Pacientes con antecedentes de síndrome de QT largo o cuyo QTc determinado en la Visita 2 (Día -14) (método de Fridericia) esté prolongado (> 450 mseg para hombres y mujeres) según confirmación del asesor de ECG central.
5. Pacientes que tengan una anomalía clínicamente significativa en el ECG de la Visita 2, que a criterio del investigador pueda constituir un posible riesgo si se incluye en el estudio. (Estos pacientes no deben ser seleccionados nuevamente).
6. Pacientes con diabetes Tipo I o Tipo II no controlada.
7. Pacientes que no hayan conseguido un resultado de espirometría en la Visita 2 de acuerdo con los criterios de la ATS/ERS para aceptabilidad y repetibilidad.
8. Pacientes con glaucoma de ángulo estrecho, hiperplasia prostática sintomática u obstrucción de cuello de vejiga o alteración renal de moderada a grave o retención urinaria.
9. Pacientes con antecedentes de cáncer de cualquier sistema
10. Pacientes que, a criterio del investigador, tengan una anomalía de laboratorio clínicamente significativa
11. Pacientes incapaces de utilizar un diario del paciente electrónico.
12. Pacientes que se sabe son, en opinión del investigador, no fiables o no cumplidores.
13. Pacientes con un índice de masa corporal (IMC) de más de 40 kg/m2.

E.5 End points

E.5.1

Primary end point(s)

Demostrar que QVA149 110/50 µg q.d. es superior a placebo en términos de mejoría de la disnea notificada por el paciente evaluada mediante el BDI/TDI (versión SAC) tras 6 semanas de tratamiento.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 semanas

E.5.2

Secondary end point(s)

Evaluar QVA149 110/50 µg q.d. en comparación con placebo y tiotropio 18 µg q.d. tras 6 semanas de tratamiento en términos de;
? FEV1 AUC 0-4 hrs estandarizado
? FVC AUC 0-4 hrs estandarizado
? El cambio medio desde la basal en las actividades de la mañana utilizando el Cuestionario de Capacidad de la Vida Diaria durante la Mañana (CDLM)
? El cambio medio desde la basal en número de inhalaciones de medicación de rescate
? Seguridad y tolerabilidad (acontecimientos adversos, analíticas de laboratorio, ECGs, y constantes vitales)

E.5.2.1

Timepoint(s) of evaluation of this end point

6 semanas

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

Yes

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

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

E.8.1.6

Cross over

Yes

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.8.2.4

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

Canada

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

LVLS

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:

234

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

234

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

F.3.3.1

Women of childbearing potential not using contraception