Clinical Trials Register

Summary
EudraCT Number:	2008-007944-33
Sponsor's Protocol Code Number:	CQAB149B2348
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-02-12
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

Czechia - SUKL

A.2

EudraCT number

2008-007944-33

A.3

Full title of the trial

A phase IIIb multicenter, 52 week treatment, randomized, blinded, double dummy, parallel group efficacy study comparing the effect of inhaled indacaterol 150 μg o.d. vs inhaled tiotropium 18 μg o.d. on lung function, rate of exacerbations and related outcomes in patients with COPD

Multicentrické, randomizované, zaslepené, dvojitě maskované, 52 týdenní klinické hodnocení fáze IIIb probíhající v paralelních skupinách porovnávající účinek inhalovaného indacaterolu v dávce 150 μg jednou denně oproti inhalovanému tiotropiu 18 μg jednou denně na plicní funkce, výskyt exacerbací a související léčebné cíle u pacientů s CHOPN.

A.3.1

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

Comparison of Indacaterol and Tiotropium on Lung Function and Related Outcomes in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Porovnání působení indakaterolu a tiotropia na funkci plic a související výstupy u pacientů s chronickou obstrukční plicní nemocí (CHOPN).

A.3.2

Name or abbreviated title of the trial where available

INVIGORATE

A.4.1

Sponsor's protocol code number

CQAB149B2348

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	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 Services 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 s.r.o.
B.5.2	Functional name of contact point	Informační služba - klin. hodnocení
B.5.3	Address:
B.5.3.1	Street Address	Na Pankráci 1724/129
B.5.3.2	Town/ city	Praha 4
B.5.3.3	Post code	140 00
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420225 775 207
B.5.5	Fax number	+420225 775 205
B.5.6	E-mail	dotazy.klinickehodnoceni@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	Yes
D.2.1.1.1	Trade name	Onbrez Breezhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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	Indacaterol
D.3.9.1	CAS number	312753-06-3
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	150
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	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, using the Handihaler device
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.3.1	Product name	Tiotropium, administered using the Handihaler inhaler
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.3.8	INN - Proposed INN	Tiotropium
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	No
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

Chronic Obstructive Pulmonary Disease (COPD)

Chronická obstrukční plicní nemoc (CHOPN)

E.1.1.1

Medical condition in easily understood language

chronic airflow limitation

chronické omezení proudění vzduchu

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	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

To demonstrate non-inferiority of 150 µg o.d. of indacaterol versus tiotropium 18 µg o.d. with respect to 24 hour post dose (trough) FEV1 after 12 weeks of treatment. Trough is defined as the mean of FEV1 measurements at 23h 10 min and 23h 45 min post morning dose.

E.2.2

Secondary objectives of the trial

To demonstrate that indacaterol 150 µg o.d, is non inferior to tiotropium 18 µg o.d. with regard to the rate of exacerbations during 52 weeks of treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male and female adults aged ≥40 years, who have signed an Informed Consent form prior to initiation of any study-related procedure
2.Patients diagnosed with COPD at age 40 and over
3.Co-operative outpatients with a diagnosis of COPD (severe as classified by the GOLD Guidelines, 2007 and including:
Smoking history of at least 10 pack years, both current and ex-smokers are eligible
Post-bronchodilator FEV1 <50% and ≥30% of the predicted normal value
Post-bronchodilator FEV1/FVC <70%
A documented history of at least 1 moderate or severe exacerbation in the previous 12 months (where exacerbation is defined as worsening of 2 or more of the following major symptoms for at least 2 consecutive days:
•dyspnea
•sputum volume
•sputum purulence
AND requiring treatment with systemic corticosteroids and/or antibiotic.
OR
worsening of any 1 major symptom together with any 1 of the following minor symptoms for at least 2 consecutive days:
•sore throat
•colds (nasal discharge and/or nasal congestion)
•fever without other cause
•increased cough
•increased wheeze
AND requiring treatment with systemic corticosteroids and/or antibiotic.
COPD exacerbations are considered of moderate severity if treatment with systemic corticosteroids and/or antibiotic was required and severe if hospitalization was required also. An Emergency Room (ER) visit of longer than 24 hours will be considered a hospitalization.
(Post refers to 15 min after inhalation of 400 µg (4x100µg) of salbutamol, equivalent to 4 x 90 µg albuterol delivered at the mouthpiece, at Visit 2).

E.4

Principal exclusion criteria

1.Patients who have received systemic corticosteroids and/or antibiotics for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period
2.Patients requiring long-term oxygen therapy (>15 h a day) for chronic hypoxemia
3.Patients who have had a respiratory tract infection within 6 weeks prior to screening
4.Patients with concomitant pulmonary disease
5.Patients with a history of asthma
6.Patients with diabetes Type I or uncontrolled diabetes Type II
7.Any patient with lung cancer or a history of lung cancer
8.Any patient with active cancer or a history of cancer with less than 5 years disease-free survival time
9.Patients with a history of long QT syndrome or whose QTc interval (Fredricia’s) measured at screening is prolonged
10.Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period
11.Patients unable to successfully use a dry powder inhaler device, or perform spirometry measurements

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 týdnů

E.5.2

Secondary end point(s)

To demonstrate that indacaterol 150 μg o.d. is non inferior to tiotropium 18 μg o.d. with regard to the rate of exacerbations during 52 weeks of treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

Yes

E.8.1.7.1

Other trial design description

Dvojitě matoucí

Double dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

Yes

E.8.5

The trial involves multiple Member States

Yes

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

Argentina

Australia

Austria

Belgium

Brazil

Canada

China

Colombia

Costa Rica

Czech Republic

Denmark

Estonia

Finland

France

Germany

Hungary

Iceland

India

Israel

Italy

Latvia

Lithuania

Mexico

Netherlands

New Zealand

Peru

Philippines

Poland

Portugal

Romania

Russian Federation

Slovakia

South Africa

Sweden

Switzerland

Taiwan

Thailand

Turkey

United Kingdom

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

LPLV

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

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.1.2.1

Number of subjects for this age range:

1841

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1604

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1095

F.4.2.2

In the whole clinical trial

3500

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 52 week treatment period will not be given further access to study medication.

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

2009-03-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-03-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-07-05

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