Efficacy and safety of Symbicort® Turbuhaler® 160/4.5 µg/inhalation, two inhalations twice daily plus as-needed compared with Seretide™ Diskus™ 50/500 µg/inhalation, one inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as-needed - a 6-month randomised, double-blind, parallel-group, active controlled, multinational phase IIIB study in adult and adolescent patients with persistent asthma. - AHEAD

• Register: EUCTR
• Last refreshed on: 10 February 2014
• Main ID: EUCTR2004-004905-11-DE
• Date of registration: 26/09/2005
• Prospective Registration: No
• Primary sponsor: AstraZeneca AB
• Public title: Efficacy and safety of Symbicort® Turbuhaler® 160/4.5 µg/inhalation, two inhalations twice daily plus as-needed compared with Seretide™ Diskus™ 50/500 µg/inhalation, one inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as-needed - a 6-month randomised, double-blind, parallel-group, active controlled, multinational phase IIIB study in adult and adolescent patients with persistent asthma. - AHEAD
• Scientific title: Efficacy and safety of Symbicort® Turbuhaler® 160/4.5 µg/inhalation, two inhalations twice daily plus as-needed compared with Seretide™ Diskus™ 50/500 µg/inhalation, one inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as-needed - a 6-month randomised, double-blind, parallel-group, active controlled, multinational phase IIIB study in adult and adolescent patients with persistent asthma. - AHEAD
• Date of first enrolment: 21/06/2005
• Target sample size: 2300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-004905-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: double-dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Germany, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
For inclusion in the study run-in period, patients must fulfill all of the following criteria
at Visit 1:
1. Provision of informed consent. The signed and dated informed consent must
have been obtained before conducting any study-related procedures, including withdrawal of concomitant medication (consent can be obtained at an information visit or at Visit 1). For patients under-age, signed informed consent from both the
patient and the patient’s parent/legal guardian is required.
2. Outpatients of either sex, =12 years of age.
3. Minimum of 6 months’ documented history of asthma according to the American Thoracic Society definition (ATS 1987).
4. Pre-bronchodilatory FEV1 =50% of predicted normal values.
5. Reversible airway obstruction (according to reversibility test performed at Visit 1), defined as an increase in FEV1 =12% relative to baseline (for all patients) and for patients =18 years =200 mL after inhalation of in total 1 mg Bricanyl Turbuhaler.
6. Prescribed daily use of inhaled GCS for =3 months prior to Visit 1.
7. During the last 30 days prior to Visit 1, the daily prescribed dose of inhaled GCS should have been constant and between:
- 400-1000 µg metered dose, or the corresponding delivered dose, in combination with LABA
- 800-1600 µg metered dose, or the corresponding delivered dose, if used
without LABA.
8. A history of at least one clinically important asthma exacerbation, as judged by the investigator, between =1 but =12 months prior to Visit 1.

To be randomised to the treatment period, the following criteria must be fulfilled at Visit 2:
9. Use of as-needed medication on at least 5 of the last 7 days of the run-in period.
10. The patient must not have taken more than 8 inhalations of as-needed medication on any day during the run-in period.
11. The patient must not have had a clinically important asthma exacerbation, as
judged by the investigator, during the run-in period.
12. Ability to fill in the diary correctly, and to use peak flow meter, Turbuhaler and
Diskus inhalers correctly.
13. The patient must still be eligible for the study in accordance with the exclusion criteria.

Are the trial subjects under 18? yes
Number of subjects for this age range:
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) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Known or suspected hypersensitivity to active substance or lactose monohydrate.
2. Respiratory infection affecting the asthma, as judged by the investigator, within
30 days prior to Visit 1.
3. Intake of oral, rectal, or parenteral GCS within 30 days prior to Visit 1.
4. Use of any ß-blocking agent, including eye-drops.
5. A history of smoking =10 pack-years (one pack-year = one pack (20 cigarettes)
per day for one year or equivalent).
6. Pregnancy, breast-feeding, or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator.
7. Any significant disease or disorder (eg, cardiovascular, pulmonary other than
asthma, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine,
metabolic, malignant, psychiatric, major physical impairment) which, in the
opinion of the investigator, either put the patient at risk because of participating
in the study or may influence the results of the study, or the patient’s ability to
participate in the study.
8. Any non-asthma-related clinically significant abnormal finding in physical
examination or vital signs at Visit 1, as judged by the investigator.
9. Suspected poor capability, as judged by the investigator, to follow instructions of the study, eg, because of a history of alcohol or drug abuse.
10. Planned in-patient hospitalisation during the course of the study.
11. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational study site).
12. Previous allocation of randomisation code in the study.
13. Participation in a clinical study during the course of this study or within 30 days prior to Visit 1.
14. Inability to tolerate withdrawal of asthma therapy as required for the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

This is a Phase IIIB study to be performed in adult and adolescent asthmatic patients.
Classification code 10003553

Intervention(s)

Product Name: Symbicort Turbuhaler 160/4.5 µg/inhalation
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: budesonide
CAS Number: 51333-22-3
Other descriptive name: budesonide 160µg/inhalation
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 160-
INN or Proposed INN: formoterol fumarate dihydrate
CAS Number: 43229-80-7
Other descriptive name: formoterol 4.5 µg/inhalation
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 4.5-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: Seretide Diskus 50/500µg/inhalation
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: salmeterol xinafoate
Other descriptive name: salmeterol 50µg/inhalation
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: fluticasone propionate
Other descriptive name: fluticasone 500µg/inhalation
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Product Name: Terbutaline Turbuhaler 0.4mg/inhalation
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: terbutaline sulfate
CAS Number: 2031-32-5
Other descriptive name: terbutaline 0.4mg/inhalation
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.4-

Primary Outcome(s)

Secondary Objective: The secondary objective of the study is to investigate safety by assessing the nature, incidence, and severity of adverse events within the treatment groups.

Primary end point(s): Primary endpoint is time to first severe asthma exacerbation.

A severe asthma exacerbation is defined as deterioration in asthma leading to at least one of the following:
- hospitalisation/emergency room (or equivalent) treatment due asthma
- oral GCS treatment due to asthma for at least 3 days.

Main Objective: The primary objective of this study is to compare the efficacy of two inhalations of Symbicort Turbuhaler 160/4.5 µg/inhalation twice daily plus Symbicort Turbuhaler 160/4.5 µg/inhalation as-needed, with one inhalation of Seretide Diskus 50/500 µg/inhalation twice daily plus terbutaline Turbuhaler 0.4 mg/inhalation as-needed in patients with persistent asthma by evaluation of time to first severe asthma exacerbation as the primary outcome variable.

Secondary ID(s)

N/A

D5890C00002