Clinical Trials Register

Summary
EudraCT Number:	2011-000960-93
Sponsor's Protocol Code Number:	NVA237A2314
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-29
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

Latvia - SAM

A.2

EudraCT number

2011-000960-93

A.3

Full title of the trial

A 12-week treatment, randomized, blinded, double-dummy, parallel-group study to assess the efficacy, safety, and tolerability of NVA237 (50 μg o.d.) compared to tiotropium (18 μg o.d.) in patients with chronic obstructive pulmonary disease (COPD)

A.3.1

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

Efficacy, safety, and tolerability of NVA237 compared to tiotropium in patients with chronic obstructive pulmonary disease (COPD)

A.4.1

Sponsor's protocol code number

NVA237A2314

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 Pharmaceuticals UK Limited
B.5.2	Functional name of contact point	Marie Campbell
B.5.3	Address:
B.5.3.1	Street Address	Wimblehurst Road
B.5.3.2	Town/ city	Horsham, West Sussex RH12
B.5.3.3	Post code	5AB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441403 323889
B.5.5	Fax number	+441403 323054
B.5.6	E-mail	marie.campbell@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	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.3.9.3	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	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.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 Handihaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Boeringer Ingelheim
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	Spiriva Handihaler
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	TIOTROPIUM BROMIDE
D.3.9.1	CAS number	139404-48-1
D.3.9.4	EV Substance Code	SUB11095MIG
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

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	15.0
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 NVA237 50 μg o.d. versus tiotropium 18 μg o.d. with respect to trough Forced Expiratory Volume in one second (trough FEV1) after 12 weeks (84 days) of treatment in patients with moderate to severe COPD (GOLD, 2010). Trough refers to the mean of FEV1 at 23h 15 mins and 23h 45 mins after the morning dose of study drug.

E.2.2

Secondary objectives of the trial

To demonstrate superiority of NVA237 (50 μg o.d.) vs. tiotropium (18 μg o.d.) on trough FEV1 after 12 weeks of treatment in patients with moderate to severe COPD if the primary objective of non-inferiority is reached.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria: To be eligible, patients have to fulfill all the criteria.
•Patients with moderate to severe stable COPD (Stage II or Stage III) according to the current GOLD Guidelines (GOLD 2010).
•Patients with a post-bronchodilator FEV1 ≥ 30% and < 80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70 at screening.
•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 yrs, or ½ pack/day x 20 yrs).
•Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3.

Other protocol-defined inclusion criteria may apply

E.4

Principal exclusion criteria

1. Pregnant or nursing (lactating) women.
2. Patients who, in the judgment of the investigator, or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition before Visit 1.
3. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).
4. Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined exclusion criteria may apply

E.5 End points

E.5.1

Primary end point(s)

Trough Forced Expiratory Volume in 1 Second (FEV1)

E.5.1.1

Timepoint(s) of evaluation of this end point

Timeframe: At 12 weeks

E.5.2

Secondary end point(s)

a. Transition Dyspnea Index (TDI) Focal Score
b. The mean change from baseline in the daily number of puffs of rescue medication
c. The mean change from baseline in the daytime number of puffs of rescue medication.
d. The mean change from baseline in the nighttime number of puffs of rescue medication
e. The percentage of ‘days with no rescue use’
f. Mean trough FEV1
g. Mean peak FEV1
h. FEV1
i. Forced Vital Capacity (FVC)
j. Inspiratory Capacity (IC)
k. FEV1 AUC (5min-4h)
l. Percentage of nights with ‘no nighttime awakenings’
m. Percentage of days with ‘no daytime symptoms’
n. Percentage of ‘days able to perform usual daily activities’
o. Symptom scores
p. Time to first moderate /severe COPD exacerbation
q. Rate of moderate / severe COPD exacerbations
r. Safety variables
s. Electrocardiogram (ECG)
t. Vital Signs (Blood pressure and radial pulse)
u. Laboratory Data
v. Quality of Life Assessment with St George’s Respiratory Questionnaire (SGRQ)

E.5.2.1

Timepoint(s) of evaluation of this end point

a. Timeframe: At 12 weeks
b. c. d. e. Timeframe: Over 12 weeks
f. g. Timeframe: Day 1; Week 4
h. i. j. Timeframe: At individual time-points on Day 1, Week 4 and Week 12
k. Timeframe: Day 1 and Week 12
l. m. n. o. p. q. r. Timeframe: Over 12 weeks
s. Timeframe: Day 1 and Week 12
t. Timeframe: At individual time-points on Days 1, 2, 28,29,84
u. v. Timeframe: 12 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

Yes

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

Yes

E.8.1.7.1

Other trial design description

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.8.2.4

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

Canada

Croatia

Guatemala

India

Korea, Republic of

Latvia

Philippines

South Africa

Taiwan

Turkey

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

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

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:

330

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

330

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

290

F.4.2.2

In the whole clinical trial

660

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 treatment period will not be given further access to NVA237 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.

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

2012-05-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-01-17

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