Patients with moderate persistent bronchial asthma and homozygous for arginine at the 16th position of the beta-2-adrenergic receptor MedDRA version: 9.0 Level: LLT Classification code 10003555
Conditions
Sponsors
Boehringer Ingelheim Pharma GmbH & Co.KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be homozygous for arginine at the 16th amino acid position of the ß2 adrenergic receptor (B16 Arg/Arg) 2. All patients must sign and date an Informed Consent form for the study consistent with ICH-GCP guidelines and local legislation prior to any study related procedures which includes medication washout and restrictions 3. Male or female outpatients between 18 and 65 years 4. Patients must have a documented history of asthma and must be current non-smokers or ex-smokers with no more than 10 pack years 5. All patients must be on a maintenance treatment with inhaled corticosteroids with a total daily dose of 400 - 1000 mcg budesonide or equivalent within the last 3 months and with a stable dose within the last 3 weeks 6. Two groups of patients are eligible for this study depending on their LABA pre-treatment: • Patients who are on a maintenance treatment with LABAs with a total daily dose of at least 100 µg salmeterol or at least 18 µg formoterol within the last 3 months and a stable dose within the last 3 weeks are eligible if they meet the following spirometric criterion: Pre-bronchodilator FEV1 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with a significant disease other than asthma; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient’s ability to participate in the study. 2. Patients with a recent history (i.e., six months or less) of myocardial infarction 3. Patients who have been hospitalized for heart failure (NYHA class III or IV) within the past year 4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year 5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed. 6. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) 7. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis 8. Patients with known active tuberculosis 9. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1. 10. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to visit 1 or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study. 11. Patients who are being treated with beta-blocker medication. Cardio-selective beta-blocker eye medication for treatment of non-narrow angle glaucoma are allowed. 12. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within 4 weeks prior to visit 1 13. Patients who were treated with cromolyn sodium or nedocromil sodium within 2 weeks prior to visit 1 14. Patients who were treated with oral betamimetics within 2 weeks prior to visit 1 15. Patients who were treated with oral corticosteroids within 4 weeks prior to visit 1 16. Patients who were treated with theophylline within 2 weeks prior to visit 1 17. Patients who were treated with leucotriene modifiers within 4 weeks prior to visit 1 18. Patients who were treated with omalizumab within 4 weeks prior to visit 1 19. Patients with known hypersensitivity to anticholinergic drugs or any other components of the inhalation solution used in the Respimat® inhaler 20. Patients with known hypersensitivity to salmeterol xinafoate or any other components of the salmeterol MDI 21. Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are not surgically sterile; or are nursing or pregnant; or are of child-bearing potential and are not practicing acceptable means of birth control, do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable means of birth control include the transdermal patch, oral, implantable or injectable contraceptives, Intra Uterine Devices (IUDs), condoms, sexual abstinence and vasectomised partner. No exceptions will be made. 22. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to visit 1 23. Patients with previous participation (receipt of randomised treatment) in this study 24. Patients who are currently partici
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of this study is to show non-inferiority of tiotropium versus salmeterol in morning peak expiratory flow after 16 weeks of treatment. Superiority of tiotropium versus placebo should also be demonstrated;Secondary Objective: To investigate efficacy and safety of tiotropium compared to salmeterol using the following secondary endpoints: Daily morning and evening peak expiratory flow, peak expiratory flow variability and forced expiratory volume in one second (FEV1), Daily questionnaire on asthma control, Morning pre-dose FEV1 and morning pre-dose FVC on study visits, Mini-Asthma Quality of Life Questionnaire on study visits, Vital signs and adverse events, Physical examination and 12-lead ECG at study end compared to the beginning of the study ;Primary end point(s): Primary endpoint of this study is the change in mean weekly morning peak expiratory flow from baseline to the last week of treatment. Baseline is defined as the last week prior to randomisation visit | — |
Countries
Austria, Denmark, Finland, Germany, Greece, Italy, Spain, United Kingdom
Outcome results
None listed