Clinical Trials Register

Summary
EudraCT Number:	2013-002664-10
Sponsor's Protocol Code Number:	CNVA237B2301
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-03-04
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

Finland - Fimea

A.2

EudraCT number

2013-002664-10

A.3

Full title of the trial

A randomized, double-blind, parallel group, 52-week study evaluating the efficacy, safety and
tolerability of NVA237 in patients with poorly controlled asthma

A.3.1

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

Study of efficacy and safety of NVA237 in patients with poorly controlled asthma

A.4.1

Sponsor's protocol code number

CNVA237B2301

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 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 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	Yes
D.2.1.1.1	Trade name	Seebri Breezhaler, Enurev Breezhaler and Tovanor 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	glycopyrronium bromide
D.3.2	Product code	NVA237B
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.3.11 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

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma

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	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
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 the superiority of NVA237 50 μg o.d. compared to placebo in addition to background therapy with LABA/ ICS (≥ 800 μg/day of budesonide or equivalent) in terms of trough FEV1 (the mean of values 23h 15min and 23h 45min post dosing) after 26 weeks of treatment in patients with asthma, who are poorly controlled despite treatment with LABA/ICS (≥ 800 μg/day of budesonide or equivalent).

E.2.2

Secondary objectives of the trial

Key:
Demonstrate superiority of NVA237 50 μg od compared to pbo in addition to background therapy with LABA/ ICS (≥ 800 μg/day of budesonide or equivalent) for:
• Time to 1st moderate or severe asthma exacerbation (52wks treatment)
• ACQ-7 - wk26

Secondary:
Compare efficacy NVA237 50 μg o.d. to pbo in addition to background therapy with LABA/ ICS (≥ 800 μg/day of budesonide or equivalent) for:
• AQLQ(S) - 52wks treatment
• SGRQ - 52wks treatment
• ACQ-7, ACQ-6, ACQ-5 - 52wks treatment
• Peak FEV1, FEV1 AUC0-3h post-dose, and mean pre-dose FEV1 - 52wks treatment
• Trough FEV1 - 52wks treatment
• FEV1 & FVC - individual timepoints
• Morning & evening mean PEF (e-diary)
• Asthma symptoms measured (ACD e-diary)
• Rescue medication (e-diary)
• Rate of moderate/severe asthma exacerbations
• Time to 1st severe asthma exacerbation, and rate of severe asthma exacerbations
• Time to 1st asthma exacerbation of any severity and rate of asthma exacerbations of any severity

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Written informed consent must be obtained before any assessment is performed;
Male and female adult patients aged 18 to <75 years;
Patients with a diagnosis of asthma (according to GINA 2012) for a period of at least 5 years prior screening;
The diagnosis of asthma must have been made before the patient was 40;
Increase in forced expiratory volume in 1 second (FEV1) of ≥ 12% and ≥ 200 mLs within 30 minutes after administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose);
Prebronchodilator FEV1 of ≥ 50 and ≤ 80% of the predicted normal value for the patient;
Patients who qualify for treatment (according to GINA 2012) and have been treated with a stable dose of a fixed dose inhaled corticosteriod (ICS) and long-acting β2 agonist (LABA) combination for at least 4 weeks prior to screening;
Patient must be using a total daily dose of ICS of ≥800 μg/day of budesonide of equivalent;
All patients must be symptomatic with a mean ACQ-5 score ≥ 1.5 at Visit 101 and Visit 102;
A documented history of one or more asthma exacerbations in the previous 12 months that required either treatment with additional or increased dose of systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment, or intubation.

E.4

Principal exclusion criteria

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: Muscarinic antagonist agents, sympathomimetic amines, lactose or any of the other excipients of the study drug, long and short acting beta-2 agonists, corticosteroids;
Women of child-bearing potential;
Resting QTcF ≥ 450 ms (male) or ≥ 460 ms (female) at Visit 101 (assessed by central reader) and at Visit
102 (assessed by investigator at the site);
Patients with a body mass index (BMI) of more than 40 kg/m2;
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, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment;
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);
Patients who have had an asthma exacerbation that required either treatment with additional or increased dose of systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment, or intubation in the 6 weeks prior to screening; Patients who have smoked or inhaled tobacco products within the 6 month period prior to screening, or who have a smoking history of greater than 10 pack years (Note:10 pack years = 1 pack /day x 10 yrs., or ½ pack/day x 20 yrs.);
Patients with a history of chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, and tuberculosis (unless tuberculosis is confirmed as no longer active by imaging);
Patients on Maintenance Immunotherapy (desensitization) for allergies must have been so for at least 3 months prior to run-in, and must be expected to remain unchanged throughout the course of the study;

E.5 End points

E.5.1

Primary end point(s)

Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 26:
Spirometry testing will be performed in accordance with American
Thoracic Society standards. Trough FEV1 defined as the mean of two
measurements at 23 hours 15 minutes and 23 hour 45 minutes post
dosing.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 26

E.5.2

Secondary end point(s)

Time to First Moderate or Severe Asthma Exacerbation Over 52 Weeks of Treatment:
Asthma exacerbations are considered to be moderate if treatment with rescue systemic corticosteroids for greater than or equal to 3 days as outpatient or less than or equal to 24 hour emergency room visit was required. Asthma exacerbations are considered severe if treatment with rescue systemic corticosteroids for greater than or equal to 3 days and
hospitalization or emergency department visit greater than 24 hours were required or death due to asthma. The time to the first moderate or severe asthma exacerbation is the study day on which the patient experienced first moderate or severe asthma exacerbation.

For detailed list see full protocol

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

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)

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

173

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

Belgium

Bulgaria

Canada

Ireland

Italy

Austria

Croatia

Netherlands

Portugal

Romania

Slovakia

Argentina

Brazil

Colombia

Estonia

Finland

Germany

Hungary

India

Latvia

Lithuania

Spain

Mexico

Philippines

Serbia

Slovenia

South Africa

Turkey

United Kingdom

United States

Vietnam

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

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:

1602

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

336

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

947

F.4.2.2

In the whole clinical trial

1938

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)

The Investigator must provide follow-up medical care for all patients who are prematurely withdrawn from the study, or must refer them for appropriate ongoing care, according to their individual medical needs. At the time of study completion patients will not be given any additional study drug since (1) NVA237 will not be approved in this indication by regulatory agencies at the time of study completion and (2) there are alternative medications commercially available for this indication.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Brigham and Women's Hospital
G.4.3.4	Network Country	United States

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-03-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-12-18

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