This is a Phase IIIB trial to be conducted in adult asthmatic patients. Classification code 10003553
Conditions
Interventions
Trade Name: Symbicort Turbohaler 160/4,5 Mikrogramm/Dosis Pulver zur Inhalation
Product Name: Symbicort Turbuhaler 160/4.5µg/inhalation
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: bud
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study the patient must fulfill all of the following criteria at enrolment (visit 1): 1. Signed and dated informed consent. This can either be obtained at the information visit or at visit 1 but must be obtained before conducting any study-related procedures, including withdrawal of concomitant medication. 2. Outpatients of either gender, 18-65 years of age. 3. Minimum of 6 month’s documented history of asthma according to the American Thoracic Society definition. 4. FEV1 =60% of predicted normal value pre-bronchodilator. 5. Ability to use Turbuhaler and a peak expiratory flow (PEF) meter. 6. Reversible airway obstruction (according to reversibility test performed at visit 1), defined as an increase in FEV1 =12% relative baseline and =200 ml after inhalation of in total 400 µg Ventolin Evohaler. (If this is not achievable, see Inclusion No. 11 below). 7. Prescribed daily use of inhaled GCS for =3 months prior to visit 1. 8. Patient considered capable, as judged by the investigator, to undergo a bronchoscopy. 9. During the last month prior to visit 1, the daily prescribed dose of inhaled GCS should have been constant and between: - 400-1000 µg metered dose or corresponding delivered dose in combination with LABA or - 800-1600 µg metered dose or corresponding delivered dose if used without LABA. 10. Successful sputum induction. If not, re-schedule the patient for an extra sputum induction. For randomisation in the study the patient must fulfill all of the following criteria at visit 2, 12-16 days after induced sputum performance. 11. A mean mPEF during the last 7 days of the run-in period (excluding the value obtained in the morning of visit 2) between 50-85% of postbronchodilatory PEF obtained after administration of inhaled SABA at visit 1. (see inclusion No. 6). 12. Use of as-needed medication on at least 4 of the last 7 days of the run-in period, or Asthma symptoms on at least 4 of the last 7 days of the run-in period, excluding the value obtained in the morning of visit 2. 13. Ability to fill in a diary card correctly. Baseline diary card must be recorded for at least 8 of the last 10 days of the run-in period. 14. The patient must not have taken more than 10 inhalations of as-needed medication on any single day during the run-in period. 15.The patients must not have had a clinically important asthma exacerbation, as judged by the investigator, during the run-in period. 16. Normal findings in laboratory variables including platelet count, prothrombin time PT) preferably reported as an International Normalized ratio (INR), partial thromboplastin time (PTT), ECG, body temperature, oxygen saturation (SaO2) or vital signs, as judged by the investigator (to be fulfilled before the bronchial biopsy surgery) 17. A successful bronchial biopsy. Are the trial subjects under 18? no 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. Known or suspected hypersensitivity to study therapy or excipients. 2. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the investigational site) 3. Respiratory infection affecting the asthma, as judged by the investigator, within 30 days prior to visit 1. 4. Previous allocation of randomisation code in the present study. 5. Intake of oral, rectal or parenteral GCS within 30 days prior to visit 1. 6. Use of any ß -blocking agent, including eye-drops. 7. Any of the following: - Current smoker - Patient with a history of smoking for more than 10 pack years (one pack year = 1 pack (20 cigarettes) per day for 1 year or equivalent) - Ex-smoker since less than 1 year. 8. History of bleeding diathesis 9. Pregnancy, breast-feeding, or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures. Acceptable contraceptive methods are those, which result in an failure rate below 1 %´, if constantly and correctly used. Examples are implants, combined oral contraceptives, some intrauterine devices, sexual abstinence or a sterilised partner. 10. 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. 11. Planned hospitalization during the course of the study. 12. Any non-asthma related clinically significant abnormal finding in physical examination or vital signs at visit 1, as judged by the investigator. 13. Suspected poor capability, as judged by the investigator, to follow instructions of the study, eg, because of a history of alcohol or drug abuse. 14. Participating in another clinical trial within 30 days prior to visit 1 or planned participation in another clinical trial during the course of the study. 15. Inability to tolerate withdrawal of asthma therapy as required for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to compare the anti-inflammatory effects of Symbicort® Single Inhaler Therapy (Symbicort Turbuhaler® 160/4.5 µg/inhalation b.i.d. plus as-needed) versus a fixed dose treatment that includes both Symbicort Turbuhaler (320/9 µg/inhalation b.i.d.) and Pulmicort® Turbuhaler (400 µg/dose b.i.d.) plus Terbutaline Turbuhaler (0.4 mg/inhalation as-needed) on the immunopathology and remodelling of the asthmatic lung.;Secondary Objective: The secondary objective of the study is to evaluate safety by investigating the nature, incidence, severity of AEs, and changes in vital signs within the treatment groups. ;Primary end point(s): Primary outcome variables: - Change from visit 2 to visit 8 in the number of eosinophils per area subepithelial tissue in bronchial biopsies. - Change from visit 1 to the mean of visit 4-7 in number of eosinophils in induced sputum, measured as % of number of inflammatory cells. | — |
Countries
Germany, Spain, Sweden, United Kingdom
Outcome results
None listed