Clinical Trials Register

Summary
EudraCT Number:	2008-006869-86
Sponsor's Protocol Code Number:	D589LC00001
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:	2008-12-29
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2008-006869-86

A.3

Full title of the trial

A comparison of Symbicort® Maintenance and Reliever Therapy (Symbicort Turbuhaler® 160/4.5 mg, one inhalation bid plus as-needed) and Symbicort Turbuhaler 160/4.5 mg, one inhalation bid plus terbutaline Turbuhaler 0.4 mg/inhalation as needed, for treatment of asthma – a 12-month, randomized, double-blind, parallel group, active-controlled, multinational phase III study in asthmatic patients aged 16 years and above.

A.3.2

Name or abbreviated title of the trial where available

SAKURA

A.4.1

Sponsor's protocol code number

D589LC00001

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Symbicort Turbuhaler 160/4.5 µg/inhalation
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca Kft.
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.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	51333223
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	160
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FORMOTEROL FUMARATE
D.3.9.1	CAS number	43229807
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	4.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Terbutaline Turbuhaler 0.4 mg/inhalation
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	TERBUTALINE SULFATE
D.3.9.1	CAS number	23031325
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.4
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma

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 primary objective of this study is to compare the efficacy of Symbicort® Maintenance and Reliever Therapy (SMART) (Symbicort Turbuhaler® 160/4.5μg, one inhalation bid plus as needed) with Symbicort Turbuhaler 160/4.5μg, one inhalation bid plus terbutaline Turbuhaler 0.4 mg as needed, as asthma therapy by evaluation of time to first asthma exacerbation.

E.2.2

Secondary objectives of the trial

The secondary objective of the study is to investigate safety of Symbicort SMART and of Symbicort 160/4.5 μg, one inhalation bid plus terbutaline Turbuhaler 0.4 mg as needed in terms of adverse events, laboratory variables, morning p-cortisol, 12-lead ECG, pulse rate and blood pressure.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of signed and dated informed consent at Visit 1 and prior to any study specific procedures. For patients under-age, signed informed consent from both the patient and the patient’s parent/legal guardian is required.

2. Outpatients of either gender aged ≥16 years at Visit 1

3. Diagnosis of asthma according to GINA 2007 with a documented history of at least 6 months duration prior to Visit 2

4. FEV1 ³ 50% of predicted normal value pre-bronchodilator

5. Reversible airway obstruction (according to a reversibility test performed at Visit 2), defined as an increase in FEV1 ≥12% relative to baseline for all patients 15-30 minutes after inhalation of in total 2 x 0.4 mg terbutaline (delivered dose) Turbuhaler

6. Prescribed use of inhaled GCS (any brand) for at least 12 weeks prior to Visit 2

7. The daily prescribed dose of inhaled GCS during the last 4 weeks prior to Visit 2 should have been constant and
at least 400 μg/day of fluticasone or Qvar,
at least 600 μg/day of budesonide,
at least 1000 μg/day of any other beclometasone dipropionate (BDP),
or equivalent dose of any other inhaled GCS (GINA 2007)

8. A history of at least 1 asthma exacerbation, as defined in Section 3.1, the last 12 months prior to Visit 2

For inclusion in the study treatment period patients must fulfill the following criteria at Visit 3:

9. Use of as-needed medication due to asthma symptoms on at least 5 of the last 7 days of the run-in period, not including the day of Visit 3

10. Capable of using a PEF meter and Turbuhaler and correctly filling in the diary

11. Morning PEF values recorded for at least 8 of the last 10 days of the run-in period (including the value obtained in the morning of Visit 3)

12. Not more than 10 inhalations of as-needed medication on any day of the run-in period

13. The patient must not have had an asthma exacerbation, as defined in Section 3.1, during the run-in period

14. The patient must be eligible for the study in accordance with the exclusion criteria

E.4

Principal exclusion criteria

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

2. Previous randomization of treatment in the present study

3. Participation in another clinical study during the course of the study or within 4 weeks before Visit 2

4. Known or suspected hypersensitivity to study therapy or excipient

5. Respiratory infection affecting the asthma, as judged by the investigator, within 4 weeks prior to Visit 2

6. Intake of oral, rectal or parenteral GCS within 4 weeks and/or depot parenteral GCS within 12 weeks prior to Visit 2

7. Use of any β-blocking agent, including eye-drops

8. Current or previous smoker with a smoking history of ≥10 pack years

9. Any significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient’s ability to participate in the study

10. Any clinically relevant abnormal findings in physical examination, laboratory variables, vital signs or ECG at Visit 2, which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study

11. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator

12. Planned hospitalisation during the study

13. Suspected poor capability, as judged by the investigator, of following instructions of the study

E.5 End points

E.5.1

Primary end point(s)

Time to first asthma exacerbation

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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.8.5.1

Number of sites anticipated in the EEA

140

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

Information not present in EudraCT

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

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

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	Yes
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)	Yes
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
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	110
F.4.2	For a multinational trial
F.4.2.1	In the EEA	110
F.4.2.2	In the whole clinical trial	2400

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

2009-02-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-02-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-02-23

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