Clinical Trials Register

Summary
EudraCT Number:	2012-005102-22
Sponsor's Protocol Code Number:	CQVA149A2328
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-20
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-005102-22

A.3

Full title of the trial

A 12-week treatment, multi-center, randomized, double-blind, double-dummy, parallel-group study to assess the efficacy, safety and tolerability of QVA149 compared to fluticasone/salmeterol 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

Study of efficacy and safety of QVA149 compared to standard of care, a
combination of fluticasone/salmeterol, in patients with moderate to severe
COPD

A.4.1

Sponsor's protocol code number

CQVA149A2328

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 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 Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41613241111
B.5.5	Fax number	+41613248001
B.5.6	E-mail	clinicaltrial.enquiries@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.3.8	INN - Proposed INN	indacaterol
D.3.9.1	CAS number	753498-25-8
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.3.8 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.3.9.3	Other descriptive name	GLYCOPYRRONIUM BROMIDE
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.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	Advair Diskus
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXOSMITHKLINE
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Advair Diskus
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	FLUTICASONE
D.3.9.1	CAS number	90566-53-3
D.3.9.4	EV Substance Code	SUB07760MIG
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	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SALMETEROL
D.3.9.1	CAS number	89365-50-4
D.3.9.4	EV Substance Code	SUB10430MIG
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.3.11 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
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

COPD patients with moderate to severe airflow limitation

E.1.1.1

Medical condition in easily understood language

COPD patients

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 twice a day as compared to
fluticasone/salmeterol 250/50 μg twice a day in COPD patients with moderate to severe
airflow limitation in terms of standardized FEV1 AUC0-12h at Week 12.

E.2.2

Secondary objectives of the trial

To evaluate the effect of QVA149 27.5/12.5 μg twice a day as compared to
fluticasone/salmeterol 250/50μg twice a day in COPD patients with moderate to severe
airflow limitation in terms of:
• Lung function:
• Trough FEV1 at Day 1 and Week 12 (mean of 23 h 15 min and 23 h 45 min post
morning dose)
• Pre-dose trough FEV1 at Week 12 (mean of 15 min and 45 min pre morning dose)
• Peak FEV1 within 4 hours post dose at Day 1 and Week 12
• AUC0-4h at Day 1 and Week 12
• FEV1 and FVC bytime point at Day 1 and Week 12
• The level of breathlessness experienced by the patients evaluated using Transition
Dyspnea Index (TDI) at Week 12
• The change in health status, based on total score of the St George’s Respiratory
Questionnaire (SGRQ) at Week 12 as compared to baseline

For more secondary objectives, please refer to the protocol

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 (GOLD 2011).
4. Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and <80%
of the predicted normal, and a post-bronchodilator 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 include:
• Total abstinence when this is in line with the preferred and usual lifestyle of the
subject (periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception).
• Female sterilization defined as surgical hysterectomy, bilateral oophorectomy, or
tubal ligation at least six weeks before taking the study treatment (Single
oophorectomy does not meet the definition of female sterilization).
• Male sterilization (at least 6 months prior to screening). For female subjects on the
study, the vasectomized male partner should be the sole partner for that subject.
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
• Use of oral, injected or implanted hormonal methods of contraception or other forms
of hormonal contraception that have comparable efficacy (failure rate <1%), for
example hormone vaginal ring or transdermal hormone contraception. In case of use
of oral contraception women should have been stable on the same pill for a minimum
of 3 months before taking study treatment.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In
the case of oophorectomy alone, only when the reproductive status of the woman has been
confirmed by follow up hormone level assessment is she considered not of child bearing
potential.
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 laboratory. These patients should not be re-screened.

For more exclusion criteria, please refer to the protocol

E.5 End points

E.5.1

Primary end point(s)

FEV1 AUC0-12h

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12

E.5.2

Secondary end point(s)

• Lung function:
• Trough FEV1 at Day 1 and Week 12 (mean of 23 h 15 min and 23 h 45 min post
morning dose)
• Pre-dose trough FEV1 at Week 12 (mean of 15 min and 45 min pre morning dose)
• Peak FEV1 within 4 hours post dose at Day 1 and Week 12
• AUC0-4h at Day 1 and Week 12
• FEV1 and FVC bytime point at Day 1 and Week 12
• The level of breathlessness experienced by the patients evaluated using Transition
Dyspnea Index (TDI) at Week 12
• The change in health status, based on total score of the St George’s Respiratory
Questionnaire (SGRQ) at Week 12 as compared to baseline
• The mean change from baseline in daily number of puffs of rescue medication at Week 12
• Symptoms reported at Week 12 using the patient electronic diary
• COPD assessment test (CAT) at Week 12
• Safety and tolerability (electrocardiograms (ECGs), laboratory tests, vital signs and
adverse events including COPD exacerbations and oral candidiasis) over 12 weeks of
treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

week 12

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tolerability

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

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

Belgium

Colombia

Czech Republic

India

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 months

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:

289

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

266

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

F.3.3.2

Women of child-bearing potential using contraception

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

555

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)

none

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

2013-03-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-10-23

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