Clinical Trials Register

Summary
EudraCT Number:	2012-003347-30
Sponsor's Protocol Code Number:	CQVA149A2337
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-14
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

Slovakia - SIDC (Slovak)

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 Slovakia s.r.o.
B.5.2	Functional name of contact point	DRA Department
B.5.3	Address:
B.5.3.1	Street Address	Galvaniho 15/A
B.5.3.2	Town/ city	Bratislava
B.5.3.3	Post code	821 04
B.5.3.4	Country	Slovakia
B.5.4	Telephone number	+421250706111
B.5.5	Fax number	+421255565886
B.5.6	E-mail	DRA.Slovakia@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.3.8	INN - Proposed INN	INDACATEROL
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	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: 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	16.1
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

1. Patients who have signed an Informed Consent Form prior to initiation
of any studyrelated procedure.
2. Male and female adults aged ≥40 years.
3. Patients with stable COPD according to the current GOLD strategy.
4. Patients with airflow limitation indicated by a post-bronchodilator
FEV1 ≥ 30% and <80% of the predicted normal, and a postbronchodilator
FEV1/FVC < 0.70 at run-in (Visit 101). Post
bronchodilator refers to 1 hour after sequential inhalation of 84 μg
ipratropium bromide (or equivalent dose) and 400 μg salbutamol (or 360
μg albuterol). Spacer devices are not permitted during reversibility
testing.
5. Current or ex-smokers who have a smoking history of at least 10 pack
years (e.g.10 pack years = 1 pack /day x 10 years, or ½ pack/day x 20
years). An ex-smoker may be defined as a subject who has not smoked
for ≥ 6 months at screening.
6. Patients with an mMRC grade 2 or greater at Visit 101.

E.4

Principal exclusion criteria

1. Pregnant or nursing (lactating) women, where pregnancy is defined
as the state of a female after conception and until the termination of
gestation, confirmed by a positive hCG (human Chorionic Gonadotropin)
laboratory test.
2. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, unless they are using
effective methods of contraception during dosing of study treatment.
Effective contraception methods are described in the protocol.
3. Patients with Type I or uncontrolled Type II diabetes.
4. Patients with a history of long QT syndrome or whose QTc measured
at Visit 101 (Fridericia method) is prolonged (>450 ms for males and
females) and confirmed by a central assessor. These patients should not
be re-screened.
5. Patients who have a clinically significant ECG abnormality at Visit 101
or Visit 102. (These patients should not be re-screened)
6. Patients who have a clinically significant laboratory abnormality at
Visit 101.
7. Patients with a body mass index (BMI) of more than 40 kg/m2.
8. Patients who have clinically significant renal, cardiovascular (such as
but not limited to unstable ischemic heart disease, NYHA Class III/IV
left ventricular failure, myocardial infarction), arrhythmia (see below for
patients with atrial fibrillation), neurological, endocrine, immunological,
psychiatric, gastrointestinal, hepatic, or hematological abnormalities
which could interfere with the assessment of the efficacy and safety of
the study treatment.
9. Patients with paroxysmal (e.g. intermittent) atrial fibrillation are
excluded. Patients with persistent atrial fibrillation as defined by
continuous atrial fibrillation for at least 6 months and controlled with a
rate control strategy (i.e., selective beta blocker, calcium channel
blocker, pacemaker placement, digoxin or ablation therapy) for at least 6
months may be considered for inclusion. In such patients, atrial
fibrillation must be present at Visit 101 and Visit 102 visits with a resting
ventricular rate < 100/min. At Visit 101 the atrial fibrillation must be
confirmed by central reading.
10. Patients contraindicated for treatment with, or having a history of
reactions/ hypersensitivity to any of the following inhaled drugs, drugs
of a similar class or any component thereof:
• anticholinergic agents
• long and short acting beta-2 agonists
• sympathomimetic amines
• lactose or any of the other excipients of trial medication
For a full list of esclusion criteria, please refer to the protocol

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

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

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)

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

France

Slovakia

Argentina

Colombia

Egypt

Guatemala

Hungary

Venezuela, Bolivarian Republic of

Mexico

Panama

Slovenia

United States

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

150

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

2012-12-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-20

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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IMP with orphan designation in the indication
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