Clinical Trials Register

Summary
EudraCT Number:	2013-001445-13
Sponsor's Protocol Code Number:	CNVA237ADE02
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-05-29
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

Germany - BfArM

A.2

EudraCT number

2013-001445-13

A.3

Full title of the trial

A randomized, double-blind, multicenter, 2-period single-dose cross-over study to assess the early bronchodilation of Glycopyrronium bromide (44 µg o.d.) compared to Tiotropium (18 µg. o.d.) in patients with moderate to severe COPD

A.3.1

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

Assessment of the early bronchodilation of Glycopyrronium bromide compared to Tiotropium in patients with moderate to severe COPD

A.3.2

Name or abbreviated title of the trial where available

FAST

A.4.1

Sponsor's protocol code number

CNVA237ADE02

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 GmbH
B.1.3.4	Country	Germany
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 GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice
B.5.3	Address:
B.5.3.1	Street Address	Roonstr. 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+491802232300
B.5.5	Fax number	+4991127312160
B.5.6	E-mail	infoservice.novartis@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	Seebri Breezhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma
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	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	16.0
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 that glycopyrronium bromide 44 µg q.d has superior efficacy compared to tiotropium 18 µg q. d. on early bronchodilation, determined by FEV1 AUC0 2h, in moderate to severe COPD patients.

E.2.2

Secondary objectives of the trial

To evaluate the effect of glycopyrronium bromide (44 μg q.d.) vs. tiotropium (18 μg q.d.) on lung function as measured by:
• Forced Spirometry: FEV1 15 min post-dose
• Bodyplethysmography
o specific airway resistance (sRaw),
o functional residual capacity (FRCpleth),
o inspiratory capacity (IC),
o residual volume (RV),
o total lung capacity (TLC)
at 30 min, 60 min, 90 min, 150 min, 210 min

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
2. Patients with moderate to severe COPD defined by a post-bronchodilator FEV1/FVC ratio of <0.70 and a post-bronchodilator FEV1 of ≤70% and FEV1 ≥ 30% of predicted normal values.
3. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)

E.4

Principal exclusion criteria

o History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
o History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
o Patients, who have already been randomized into this trial earlier must not be included a second time.
o Study personnel or first degree relatives of investigator(s) must not be included in the study.
o Patients incapable of giving full informed consent.
Women
o who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml))
o who are menstruating and capable of becoming pregnant and not practicing a medically approved method of contraception (Pearl Index <1) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women is required with sufficient lead time before inclusion

COPD specific exclusion criteria
1. Patients with Type I or uncontrolled Type II diabetes (HbA1C > 8%).
2. Patients with a history of long QT syndrome or whose QTc calculated at run-in (Bazett formula) is prolonged (>450 ms). These patients should not be re-enrolled.
3. Patients who have a clinically significant ECG abnormality at run-in.
4. Patients who have a clinically significant laboratory abnormality at run-in.
5. Patients with a body mass index (BMI) of more than 40 kg/m2.
6. 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), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or haemotological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment.
7. 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 blockers, 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 the run-in (Visit 2) with a resting ventricular rate < 100/min.
8. 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:
a. Muscarinic antagonist agents
b. long and short acting beta-2 agonists
c. sympathomimetic amines
d. lactose or any of the other excipients of the trial medication
9. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment (GFR <50 ml/min/1,732) or urinary retention. (BPH patients who are stable on treatment can be considered).
10. Patients who have not achieved acceptable spirometry results at run-in in accordance with ATS/ERS criteria for acceptability and repeatability.
11. Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening.
12. Patients who develop a COPD exacerbation between screening and prior to treatment will not be eligible but will be permitted to be re-enrolled after a minimum of 6 weeks after the resolution of the COPD exacerbation.
13. Patients who have had a respiratory tract infection within 4 weeks prior to screening.
14. Patients who develop a respiratory tract infection between screening and prior to treatment will not be eligible, but will be permitted to be re-enrolled 4 weeks after the resolution of the respiratory tract infection.
15. Patients requiring long term oxygen therapy prescribed for >12 hours per day.
16. Patients with any history of asthma.
17. Patients with an onset of chronic respiratory symptoms, including a COPD diagnosis, prior to age 40 years.
18. Patients with a blood eosinophil count > 600/mm3 during run-in.
19. Patients with allergic rhinitis who use a H1 antagonist or intra-nasal corticosteroids intermittently (treatment with a stable dose or regimen is permitted).
20. Patients with concomitant pulmonary disease.
21. Patients with clinically significant bronchiectasis.
22. Patients with a diagnosis of α-1 anti-trypsin deficiency.
23. Patients with active pulmonary tuberculosis, unless confirmed by imaging to be no longer active.
......

31. Patients with a decrease in post bronchodilator FEV1 compared to pre-bronchodilator FEV1, observed at Visit 2 during reversibility testing assessment (Appendix 6).

Other protocol-defined inclusion criteria may apply

E.5 End points

E.5.1

Primary end point(s)

Early bronchodilation determined by FEV1 AUC0 2h

E.5.1.1

Timepoint(s) of evaluation of this end point

2 h

E.5.2

Secondary end point(s)

Lung function as measured by:
• Forced Spirometry: FEV1 15 min post-dose
• Bodyplethysmography
o specific airway resistance (sRaw),
o functional residual capacity (FRCpleth),
o inspiratory capacity (IC),
o residual volume (RV),
o total lung capacity (TLC)
at 30 min, 60 min, 90 min, 150 min, 210 min

E.5.2.1

Timepoint(s) of evaluation of this end point

Forced Spirometry: FEV1 15 min post-dose
Bodyplethysmography
o specific airway resistance (sRaw),
o functional residual capacity (FRCpleth),
o inspiratory capacity (IC),
o residual volume (RV),
o total lung capacity (TLC)
at 30 min, 60 min, 90 min, 150 min, 210 min

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

E.8.1.6

Cross over

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	100
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	50
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	150

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

2013-06-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-08-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-01-09

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