Clinical Trials Register

Summary
EudraCT Number:	2012-003347-30
Sponsor's Protocol Code Number:	CQVA149A2337
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-04
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2012-003347-30

A.3

Full title of the trial

A 12-week treatment, multi-center, randomized, double-blind, parallel group, placebo and active controlled study to assess the efficacy, safety, and tolerability of QVA149 (indacaterol maleate /glycopyrronium bromide) in COPD patients with moderate to severe airflow limitation

A.3.1

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

A multi-centre randomized double blind 12-week study to assess the efficacy, safety and tolerability of QVA149 in patients with COPD who have moderate to severe airflow limitation

A.4.1

Sponsor's protocol code number

CQVA149A2337

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 Pharma Services AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma Service AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Hungária Kft., Pharma
B.5.2	Functional name of contact point	Public Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Bartók Béla út 43-47.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1114
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+361457-6500
B.5.5	Fax number	+361457-6600
B.5.6	E-mail	infoph.hungary@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.3.1	Product name	Indacaterol maleate/Glycopyrronium bromide
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.3.8	INN - Proposed INN	GLYCOPYRRONIUM BROMIDE
D.3.9.1	CAS number	596-51-0
D.3.9.2	Current sponsor code	NVA237
D.3.9.4	EV Substance Code	SUB07951MIG
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	12.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INDACATEROL MALEATE
D.3.9.1	CAS number	753498-25-8
D.3.9.2	Current sponsor code	QAB149
D.3.9.4	EV Substance Code	SUB30300
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	27.5
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)	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	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	Indacaterol
D.3.2	Product code	QAB149
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.3.9.1	CAS number	753498-25-8
D.3.9.2	Current sponsor code	QAB149
D.3.9.3	Other descriptive name	INDACATEROL MALEATE
D.3.9.4	EV Substance Code	SUB30300
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	75
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: 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	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	Glycopyrronium bromide
D.3.2	Product code	NVA237
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.3.8	INN - Proposed INN	GLYCOPYRRONIUM BROMIDE
D.3.9.1	CAS number	596-51-0
D.3.9.2	Current sponsor code	NVA237
D.3.9.4	EV Substance Code	SUB07951MIG
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	12.5
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)	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

COPD is a chronic condition of the lungs which causes people to suffer symptoms such as shortness of breath and coughing.

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the superiority of QVA149 27.5/12.5 μg b.i.d. compared to monotherapy components, QAB149 27.5 μg b.i.d. and NVA237 12.5 μg b.i.d., in terms of standardized FEV1AUC0-12 at Week 12.

E.2.2

Secondary objectives of the trial

Key secondary objective: To demonstrate the superiority of QVA149 27.5/12.5 μg b.i.d. compared to placebo at Week12 in terms of the change in Health Status, based on total score as well as the percentage of patients with clinically significant improvement, as reported by the patients using the SGRQ.
Secondary objectives
- To evaluate the superiority of QVA149 27.5/12.5 μg b.i.d., QAB149 27.5 μg b.i.d. and NVA237 12.5 μg b.i.d. compared to placebo in terms of standardized FEV1AUC0-12 at Wk 12.
- To evaluate the superiority of QVA149 27.5/12.5 μg b.i.d., QAB149 27.5 μg b.i.d. and NVA237 12.5 μg b.i.d. compared to placebo in terms of the following endpoints:
-trough FEV1 (mean of 23 h 15 min and 23 h 45 min post morning dose) at Wk 12
-pre-dose trough FEV1 (mean of 15 min and 45 min pre morning dose) at Week 12
-Trough FEV1 (mean of 23 h 15 min and 23 h 45 min post morning dose) after Day1
-FEV1 and FVC at any time point
Other secondary objectives listed in the protocol may apply

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Male and female patients that have signed informed consent and are >/= 40 years of age.
•Patients with stable Chronic Obstructive Pulmonary Disease (COPD) according to GOLD 2011.
•Patients with a post-bronchodilator Force Expiratory Volume in one second (FEV1) of >/= 30% and < 80% predicted and a post-bronchodilator FEV1/ Forced Vital capacity (FVC) <0.70.
•Current or ex-smokers who have a smoking history of at least 10 pack years.
•Patients with an mMRC grade 2 or greater.

Other protocol defined inclusion criteria may apply

E.4

Principal exclusion criteria

•Patients contraindicated for muscarinic antagonist agents and beta-2 agonists.
•Patients with a history of malignancy of any organ system, treated or untreated, within the last five years.
•Patients with narrow-angle glaucoma, Benign Prostatic Hyperplasia (BPH) or bladder-neck obstruction or moderate-severe renal impairment or urinary retention.
•Patients who had a COPD exacerbation within 6 weeks prior to screening.
•Patients who have a respiratory tract infection within 4 weeks prior to screening.
•Patients requiring long term oxygen therapy prescribed for more than 12 hour per day.
•Patients with a history of asthma.
•Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to age 40 years.
•Patients with a blood eosinophil count of greater than 600 mm/3 during run-in.
•Patients with concomitant pulmonary disease.
•Patients with a history of certain cardiovascular co-morbid conditions
•Patients with a diagnosis of alpha-1 anti-trypsin deficiency.
•Patients with active pulmonary tuberculosis.
•Patients in the active phase of a pulmonary rehabilitation programme.
•Other protocol-defined exclusion criteria may apply.

E.5 End points

E.5.1

Primary end point(s)

Standardized Forced Expiratory Volume in one second Area Under the Curve (AUC) following 12 weeks of treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timeframe : 12 weeks

E.5.2

Secondary end point(s)

1-Total St. George's Respiratory Questionnaire score
2-Trough Forced Expiratory Volume in one second
3-Pre-dose trough Forced Expiratory Volume in one second
4-Transitional Dyspnea Index focal score
5-Number of puffs of rescue medication
6-Daily symptoms score
7-Trough Forced Expiratory Volume in one second
8-Forced Expiratory Volume in one second at any time point
9-Morning symptoms score
10-Evening symptoms scores
11-Forced Vital Capacity at different time points

E.5.2.1

Timepoint(s) of evaluation of this end point

Timeframe :
1.2.3.4.5.6.7.9.10.11 : 12 weeks
8 : day 1

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

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

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.8.2.4

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

Argentina

Colombia

Egypt

France

Guatemala

Hungary

Mexico

Panama

Slovakia

Slovenia

United States

Venezuela, Bolivarian Republic of

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

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:

520

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

480

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

310

F.4.2.2

In the whole clinical trial

1000

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)

Patients completing the 12 week treatment period will not be given further access to study
drug because the risk benefit ratio will not have been substantiated by that time and there are
already other marketed therapeutic alternatives available to treat these patients. At the time of
study completion or early termination, the investigator must provide follow-up medical care
or must refer them for appropriate ongoing care.

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

2013-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-02-28

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