Clinical Trials Register

Summary
EudraCT Number:	2011-000834-12
Sponsor's Protocol Code Number:	M/34273/39
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2011-000834-12

A.3

Full title of the trial

A MULTIPLE DOSE, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO CONTROLLED, PARALLEL CLINICAL TRIAL TO ASSESS THE EFFICACY AND SAFETY OF TWICE DAILY INHALED ACLIDINIUM BROMIDE 400 μg COMPARED TO PLACEBO AND TO TIOTROPIUM BROMIDE IN PATIENTS WITH STABLE MODERATE TO SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD).

A.3.1

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

Not applicable

A.4.1

Sponsor's protocol code number

M/34273/39

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	Almirall S.A.
B.1.3.4	Country	Spain
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	Almirall S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Almirall S.A.
B.5.2	Functional name of contact point	Rosa Segarra-Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Laureano Miró 408-410
B.5.3.2	Town/ city	Sant Feliu de Llobregat, Barcelona
B.5.3.3	Post code	08980
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34932913487
B.5.5	Fax number	+34932913531
B.5.6	E-mail	rosa.segarra@almirall.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	Aclidinium Bromide
D.3.2	Product code	LAS34273
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	Aclidinium bromide
D.3.9.1	CAS number	320345-99-1
D.3.9.2	Current sponsor code	LAS34273
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	400
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.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®
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	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	Spiriva
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
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 lung disease that causes shortness of breath and coughing.
A bronchodilator helps to open your airways and makes it easier to get air in and out of the lungs.

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	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

1. To evaluate the 24h bronchodilatory efficacy of inhaled aclidinium bromide 400 μg BID versus placebo in moderate to severe COPD patients
2. To evaluate the night-time bronchodilation of inhaled aclidinium bromide 400 μg BID versus tiotropium bromide in moderate to severe COPD patients
3. To assess the safety and tolerability of inhaled aclidinium bromide 400 μg BID in the same target population.

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and non-pregnant, non-lactating females aged ≥ 40, at least 1 year post-menopausal, surgically sterile (defined as having a hysterectomy or tubal ligation), or practicing a medically approved and highly effective method of contraception. Women of childbearing potential must have a negative pregnancy test at Screening (Visit -1) and have used it for at least two months before the Screening Visit, at least one medically approved and highly effective method of birth
control defined as those which result in a low failure rate (i.e less than 1% per year) when used consistently and correctly such as implants, injectables, oral contraceptives combined with at least one barrier method, hormonal IUDs, sexual abstinence or vasectomy of the partner.
2. Patients with a clinical diagnosis of stable moderate to severe COPD, according to the GOLD guidelines: (http://www.goldcopd.com) and stable airway obstruction. Post-salbutamol FEV1/FVC < 70% at Screening Visit (Visit -1) (i.e., 100xpost-salbutamol FEV1/FVC <70%).
3. Patients whose FEV1 at Screening Visit measured between 10-15 min post inhalation of 400 μg of salbutamol is ≥ 30% and <80% of the predicted normal value (i.e., 100xobserved post-salbutamol
FEV1/ predicted FEV1 <80%).
Predicted normal values to be used for calculation purposes are to be based on European Community for Steel and Coal predicted values (Quanjer et al. 1993).
4. Patient must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria at the Screening Visit.
5. Current or former cigarette smokers with a smoking history of at least 10 pack/years. Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has
smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history). Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion
as well.
6. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent.

E.4

Principal exclusion criteria

1. History or current diagnosis of asthma.
2. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before the Screening Visit (Visit -1). Patients who develop a respiratory tract infection or exacerbation during the run-in period will be discontinued from the trial before
randomisation.
3. Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Screening Visit (Visit -1).
4. Clinically significant respiratory conditions defined as:
• Known active tuberculosis.
• History of interstitial lung or pulmonary thromboembolic disease.
• Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening Visit.
• History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc).
• History of lung transplantation.
• Patients who in the investigator’s opinion may need pulmonary rehabilitation or thoracotomy or other lung surgery during the trial.
• Patients with a history of a1-antitrypsin deficiency.
5. Use of long-term oxygen therapy (≥ 15 hours/day).
6. Patient who in the investigator’s opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening
Visit.
7. Clinically significant cardiovascular conditions defined as:
• Myocardial infarction during the previous 6 months.
• Thoracic surgery within 12 months prior to Screening Visit.
• Unstable angina, unstable arrhythmia which has required changes in the pharmacological therapy or other intervention (e.g. use of an automated implantable cardioverterdefibrillator) during the last 12 months, or newly diagnosed arrhythmia within the previous
3 months.
• Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms
at rest) according to the New York Heart Association.
8. Patients with non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
9. Patients with clinically relevant abnormalities in the results of the clinical laboratory tests, in ECG parameters, or in the physical examination at the screening evaluation (Visit -1).
10. Patients with a history (within the previous 2 years) of drug and/or alcohol abuse that may prevent compliance with trial activities.
11. Patients with any other serious or uncontrolled physical or mental dysfunction that, as judged by the investigator, could place the patient at higher risk derived from his/her participation in the study, could confound the results of the study or is likely to prevent the patient from complying with the requirements of the study or completing the study.
12. Patients with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm).
13. Patients for whom the use of anticholinergic drugs are contraindicated:
• Patients with acute urinary retention, symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma (Note: Patients with well-controlled, stable, asymptomatic benign prostatic hypertrophy are not excluded).
14. Patients unable to properly use a multidose dry powder inhaler or a pressurized metereddose inhaler (pMDI) or to use the e-diary.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in normalised FEV1 area under the curve over the 24-h period immediately after morning IMP administration (AUC0-24 ) after 6 weeks of treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to point E 5.1

E.5.2

Secondary end point(s)

Change from baseline in normalised FEV1 AUC12-24 after 6 weeks of treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to point E 5.2

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

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

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

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

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:

380

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

405

F.4.2.2

In the whole clinical trial

405

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)

Restart of medication taken by patient prior to study entry or any other
as deemed appropriate and patient will be deferred to his/her family
doctor.

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

2011-10-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-03-14

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials