Clinical Trials Register

Summary
EudraCT Number:	2014-002705-38
Sponsor's Protocol Code Number:	3103013
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:	2014-10-15
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

2014-002705-38

A.3

Full title of the trial

STUDY COMPARING BRONCHODILATOR EFFICACY OF TWO DRY POWDER INHALERS, BUDESONIDE/FORMOTEROL EASYHALER AND SYMBICORT TURBUHALER; A RANDOMISED, DOUBLE-BLIND, DOUBLE-DUMMY, MULTICENTRE, SINGLE DOSE, CROSSOVER STUDY IN ASTHMATIC SUBJECTS

A.3.1

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

Comparison of effectiveness of two different kinds of inhalers on bronchodilation in people with asthma

A.3.2

Name or abbreviated title of the trial where available

BUFODIL

A.4.1

Sponsor's protocol code number

3103013

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	Orion Corporation Orion Pharma
B.1.3.4	Country	United Kingdom
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	Orion Corporation Orion Pharma
B.4.2	Country	Finland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Orion Corporation Orion Pharma
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Orionintie 1
B.5.3.2	Town/ city	Espoo
B.5.3.3	Post code	FI-02200
B.5.3.4	Country	Finland
B.5.4	Telephone number	+358104261
B.5.5	Fax number	+358104267632
B.5.6	E-mail	clinicaltrials@orionpharma.com

D. IMP Identification
D.IMP: 1
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	SYMBICORT TURBUHALER
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	SYMBICORT TURBUHALER
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	Budesonide
D.3.9.1	CAS number	51333-22-3
D.3.9.4	EV Substance Code	SUB05955MIG
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	320
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Formoterol
D.3.9.1	CAS number	183814-30-4
D.3.9.3	Other descriptive name	FORMOTEROL FUMARATE HYDRATE
D.3.9.4	EV Substance Code	SUB25661
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	9
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	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	Bufomix Easyhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Orion Corporation
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	Bufomix Easyhaler
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	BUDESONIDE
D.3.9.1	CAS number	51333-22-3
D.3.9.4	EV Substance Code	SUB05955MIG
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	320
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Formoterol
D.3.9.1	CAS number	183814-30-4
D.3.9.3	Other descriptive name	Formoterol fumarate hydrate
D.3.9.4	EV Substance Code	SUB25661
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	9
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.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
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

Inflammation of the airways

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10006070
E.1.2	Term	Br. asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
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

The objective of the study is to confirm equivalent bronchodilator efficacy of the test product (Budesonide/formoterol Easyhaler) compared to the reference product (Symbicort Turbuhaler).

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent (IC) obtained
2. Male or female subjects aged 18-70 (inclusive) years on the screening visit.
3. Documented diagnosis of asthma for  6 months. The asthma diagnosis should be in accordance with the latest international recommendations provided by the Global Initiative for Asthma (GINA).
4. Prebronchodilator FEV1 45-90% (inclusive) of the predicted value measured on screening visit.
5. Demonstration of reversible airway obstruction:  12% and  200 ml improvement in FEV1 after inhalation of SABA within 6 months prior to screening or at the screening visit.
6. Demonstration of stepwise reversibility of airway obstruction with formoterol. Overall improvement in FEV1 at least 15% after 6 + 42 µg (metered dose, 4.5 + 31.5 µg as delivered dose) of formoterol inhaled via Turbuhaler, with a 50% additional improvement seen after the second dose.
7. Asthma should be stable on the same regular treatment (e.g. inhaled corticosteroid) for at least 4 weeks before the screening visit.
8. Asthma unlikely to exacerbate during the study (e.g. because of seasonal allergen exposure).
9. Non-smoker for at least 6 months before the screening visit.
10. Ability to use Easyhaler and Turbuhaler according to instructions.

E.4

Principal exclusion criteria

1. Hypersensitivity to any components of the preparations, i.e., budesonide, formoterol fumarate dihydrate or lactose (which contains small amounts of milk proteins).
2. Treatment with LABA within 4 weeks before screening visit and during the study.
3. Treatment with xanthine-derivatives (e.g. theophylline) within 4 weeks before screening visit and during the study.
4. Use of β -blocker within 4 weeks preceding screening visit and during the study.
5. Use of quinidine, disopyramide, procainamide, phenothiazines, terfenadine, astemizole, diphenhydramine, monoamine oxidase inhibitors, tricyclic antidepressants and use of any other drug that prolongs the QT-interval during the study.
6. Use of oral, parenteral, rectal or systemic corticosteroids within 4 weeks preceding screening visit and during the study.
7. Respiratory infection within 4 weeks preceding screening visit.
8. Smoking history of more than 10 pack-years (the equivalent of one pack per day for 10 years).
9. Abnormal ECG of clinical significance and/or corrected QT interval (calculated with the Fridericia formula [QTcF]) > 450 ms in males or > 470 ms in females on screening visit.
10. Cardiovascular, renal, neurological, liver or endocrine dysfunction or any other major concurrent illness that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the patient if he/she takes part in the study.
11. Chronic bronchitis or any other severe chronic respiratory disease other than asthma. History of cystic fibrosis or bronchiectasis.
12. Abnormal serum potassium value or other clinically significant laboratory findings on the screening visit.
13. Systolic blood pressure (BP) over 180 mmHg and/or diastolic BP over 100 mmHg at rest on the screening visit.
14. Pregnant, breast-feeding or fertile women without reliable contraception (mechanical and/or hormonal contraception, intrauterine device [IUD] or surgical sterilisation). Double method of contraception is needed when using oral or mechanical contraception; e.g. condom in conjunct with oral contraception and spermicidal product with mechanical contraception. Females of childbearing potential with no current sexual relationship can be included without contraception according to the judgement of the investigator.
15. Investigator’s suspicion of alcohol or drug abuse.
16. Previous participation in this study or participation in another clinical drug study within 4 weeks before the first study treatment administration and during the study.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is the average of 12-hour FEV1.

E.5.1.1

Timepoint(s) of evaluation of this end point

The spirometry test will be performed on each study treatment day before and 10, 20, 60, 120, 180, 240, 360, 480, 600 and 720 min after administration of the study treatment (counted from the start of the first inhalation)

E.5.2

Secondary end point(s)

Maximum FEV1 over the 12-hour serial assessments and FEV1 at 12 hours post-dose (i.e. FEV1 at the trough of the effect) will be the secondary efficacy variables.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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

E.8.1.6

Cross over

Yes

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

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:

F.1.3

Elderly (>=65 years)

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

F.4.2.2

In the whole clinical trial

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)

No plans for administration after the subject has ended the participation in the clinical trial.

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

2014-11-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-06-12

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