Clinical Trials Register

Summary
EudraCT Number:	2014-004715-37
Sponsor's Protocol Code Number:	M-34273-46
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-12-19
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2014-004715-37

A.3

Full title of the trial

A randomised, double blind, placebo controlled, parallel study to assess the benefits of aclidinium bromide in the relief of COPD symptoms including cough when administered to patients with COPD

Randomizált, kettősvak, placebokontrollos, párhuzamos vizsgálat az aklidínium-bromid előnyeinek értékelésére a COPD tünetek enyhítésében, beleértve a köhögést, amikor COPD-ban szenvedő betegeknek adják

A.3.1

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

A randomised, double blind, placebo controlled, parallel study to assess the benefits of aclidinium bromide in the relief of COPD (Chronic obstructive pulmonary disease) symptoms including cough when administered to patients with COPD

Randomizált, kettősvak, placebokontrollos, párhuzamos vizsgálat az aklidínium-bromid előnyeinek értékelésére a COPD (Krónikus obstruktív tüdőbetegség) tünetek enyhítésében, beleértve a köhögést, amikor COPD-ban szenvedő betegeknek adják

A.4.1

Sponsor's protocol code number

M-34273-46

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	AstraZeneca AB; Karlebyhus, Astraallén, Södertälje SE-151 85, Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Menarini Group through its affiliate Berlin Chemie AG
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	AstraZeneca
B.5.2	Functional name of contact point	Information Centre
B.5.6	E-mail	information.center@astrazeneca.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	Eklira Genuair
D.2.1.1.2	Name of the Marketing Authorisation holder	Almirall, S.A.
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	Aclidinium bromide 400 µg
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.3.9.2	Current sponsor code	LAS34273
D.3.9.4	EV Substance Code	SUB71687
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	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

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	17.1
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

1. To assess the effect of aclidinium bromide 400 µg administered twice a day on COPD symptoms including cough in patients with moderate COPD compared to placebo.

2. To assess the effects of aclidinium bromide 400 µg administered twice a day in cough related quality of life measures when administered to the same target population.

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A reduced group of research centres will participate in a 24-hours cough monitoring substudy. In addition to the main study assessments, all patients enrolled at the substudy centres will have ambulatory cough sound monitoring using a Vitalojak™ cough monitor (Vitalograph Ltd). Recording will cover the 24 hours preceding Visits 2, 3 and 4, and therefore will require the patient to attend additional visits to the clinic for monitor placement. Patients will be required to report the awakening time and sleep time on the days when the 24 hours cough recording takes place. Approximately 20% of all trial population will take part on this substudy.

E.3

Principal inclusion criteria

1. Adult male or non-pregnant, non-lactating female aged ≥ 40. Women of childbearing potential will follow specific study requirements.
Explanatory note: A female is considered to be of childbearing potential unless she has had a hysterectomy, is at least one year post-menopausal or has undergone tubal ligation. Women of childbearing potential are allowed to enter the trial if they show to have a negative urine pregnancy test at the Visit 1 (Screening) and are using, during the last 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 intra uterine devices (IUDs), sexual abstinence or vasectomy of the partner.

2. Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years.
Explanatory note: Ex-smoker definition includes those patients who quit smoking more than 6 months prior to the Screening Visit. 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). When the patient has been smoker during several periods of time separated by inactivity periods, the total pack years resulting from several periods of smoking will be added up.
Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.

3. Patients with a clinical diagnosis of moderate COPD, with a post bronchodilator test available within 6 months prior to Visit 1 (Screening), with FEV1 ≥50% and <80% and FEV1/FVC < 70%.
Explanatory note: COPD diagnosis according to GOLD guidelines 2014

4. Symptomatic patients with a CAT ≥ 10 at Screening and Randomisation Visit (Visit 1 and 2)
Explanatory note: CAT questionnaire cannot be repeated.

5. Clinical Diagnosis of Chronic Bronchitis (defined as “presence of cough and sputum production for at least 3 months in each of 2 consecutive years”)

6. Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained.

E.4

Principal exclusion criteria

For inclusion and randomisation in the trial, patients must NOT meet any of the following criteria at Visit 1 (Screening) and at Visit 2 prior to randomisation.

1. History or current diagnosis of asthma.

2. Patients who suffered from a moderate or severe COPD exacerbation in the last year prior to Visit 1 (Screening) or during the run-in period.

3. Patients who develop a respiratory tract infection within 6 weeks before Visit 1 (Screening) or during the run-in period.

4. Clinically significant respiratory and cardiovascular conditions thought to be contributing to cough or likely to interfere in the conduct of the study.

5.Patient who in the investigator’s opinion may need to start a pulmonay rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening Visit.

6. Use of long-term oxygen therapy.

7. Patients in non-stable treatment with angiotensin-converting enzyme inhibitors or opiates.
Explanatory note: The above medication is allowed if taken as stable for at least two months prior to Screening Visit.

8. Patients in treatment with mucolytics, antihistamines, expectorants or antitussive drugs including over-the-counter medication.

9.Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers.
Explanatory note: Patients with symptomatic sleep apnoea syndrome, any disease related with sleep disturbances such as restless-legs syndrome or somnambulism are to be excluded. However the use of continuous positive airway pressure (CPAP) is not an exclusion criteria.

10. Patient with clinically relevant abnormalities in the results of the physical examination at Visit 1 (Screening)

11. Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm).

12. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic non-stable prostatic hypertrophy.
Explanatory note: Patients with well-controlled, stable, asymptomatic benign prostatic hypertrophy are not excluded.

13. Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
Explanatory note: active hepatitis is defined as clinical symptoms associated with chronic portal inflammation with regional necrosis and fibrosis, which may progress to nodular postnecrotic cirrhosis or patients with antibody to hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) test with positive results or anti-HCV antibody and HCV RIBAHCV positive tests or genetic material (RNA) testing positive results.

14. Current diagnosis of cancer other than basal or squamous cell skin cancer.

15. Patient with any other serious or uncontrolled physical or mental dysfunction.
Explanatory note: As judged by the investigator, the dysfunction 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 (e.g. suicidal ideation, mood disorders, personal history of overdose intake).

16. Patient with a history (within 2 years prior to Screening Visit) of drug and/or alcohol abuse that may prevent study compliance based on investigator judgment.

17. Patient unlikely to be cooperative or that can not comply with the study procedures.
Explanatory note: Patients who may have difficulties to follow the treatment, complete the Patient Diaries or attend the clinic at the required times or unable to properly use a DPI or pMDI inhaler device.

18. Patient treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to Visit 1 (Screening).

19. Patient who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required stabilization periods for prohibited medication.

20. Any other conditions that, in the investigator’s opinion, might indicate the patient to be unsuitable for the study.

E.5 End points

E.5.1

Primary end point(s)

Primary efficacy endpoint:
• Change from baseline in Overall E-RS Total score (i.e. score over the whole 8 weeks study period)

E.5.1.1

Timepoint(s) of evaluation of this end point

score over the whole 8 weeks study period

E.5.2

Secondary end point(s)

Secondary efficacy endpoints:
• Change from baseline in Overall E-RS Cough and Sputum domain score.
• Change from baseline in the LCQ Total score at Week 8.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints:
• at Week 8

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

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

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)

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

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:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

250

F.4.2.2

In the whole clinical trial

250

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)

After last study procedure is performed at Visit 4, subjects should continue to take their usual medication, also allowed during the trial, and may resume other medications discontinued prior to trial enrolment (with investigator’s agreement).

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-02-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-11-17

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IMP with orphan designation in the indication
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