moderate persistent asthma MedDRA version: 14.0 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. All patients must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1). 2. Male or female patients aged between 18 and 75 years (at date of informed consent). 3. All patients must have at least a 3 month history of asthma at the time of enrolment into the trial. The diagnosis should be confirmed at Visit 1 by fulfilling inclusion criterion no. 5. 4. The initial diagnosis of asthma must have been made before the patient's age of 40. 5. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 to 30 minutes after 4 puffs of 100 µg salbutamol) resulting in a FEV1 increase of = 12% and = 200mL (see Appendix 10.3). NOTE: If this is not achieved the reversibility test may be repeated once within two weeks. 6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (as detailed in Appendix 10.3) (alone or in a fixed combination with a LABA or SABA) for at least 4 weeks prior to Visit 1. 7. All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an ACQ (see Appendix 10.4) mean score of = 1.5. NOTE: If the patient is not eligible due to the predefined score at Visit 1, the patient should not be further evaluated. If the patient is not eligible due to the predefined score at Visit 2, the patient’s Visit 2 can be repeated once for further assessment (see section 6.1). 8. All patients must have a pre-bronchodilator FEV1 = 60% and = 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to ECSC [R94-1408] (see Appendix 10.3). 9. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%. Note: If the patient is not eligible due to variation of absolute FEV1 values at Visit 2, the patient´s Visit 2 can be repeated once for further assessment. 10. Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years (see Appendix 10.3 for calculation). 11. Patients must be able to use the Respimat® inhaler correctly. 12. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required; refer to section 6.1 for instructions). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 108 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Patients with a significant disease other than asthma (which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.) 2. Patients with a clinically relevant abnormal screening (Visit 1) haematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion 1. 3. Patients with a recent history (i.e. six months or less) of myocardial infarction. 4. Patients who have been hospitalised for cardiac failure during the past year. 5. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year. 6. Patients with lung diseases other than asthma (e.g. COPD). 7. Patients with known active tuberculosis. 8. 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. 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 with known moderate to severe renal impairment (as judged by the investigator). 11. Patients with known narrow angle glaucoma or any other disease where anticholinergic treatment is contraindicated. 12. Patients with significant symptomatic prostatic hyperplasia or bladder-neck obstruction (to the discretion of the investigator). Patients whose symptoms are controlled on treatment may be included. 13. Patients with significant alcohol or drug abuse within the past two years (to the discretion of the investigator). 14. Patients who are currently in a pulmonary rehabilitation program or have completed pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening) or who will start a rehabilitation program during the study. 15. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the study medication delivery system (Respimat®/ tiotropium inhalation solution). 16. Pregnant or nursing woman. 17. Women of childbearing potential not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomised partner. Barrier methods of contraception (e.g. condom, diaphragma or occlusive cap) are accepted if used together with spermicides (e.g. foam, gel). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years. 18. Patients who have taken an investigational drug within four weeks prior to Visit 1. 19. Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2). Topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed. 20. Patients who have been treated within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of three doses of tiotropium inhalation solution (1.25, 2.5 and 5.0 µg) delivered ex mouthpiece by the Respimat® inhaler in patients with moderate persistent asthma once daily in the evening on top of inhaled corticosteroids.;Secondary Objective: Secondary objectives, assessed in patient subgroups, are: to evaluate the 24 hour exposure to tiotropium and to demonstrate 24 hour bronchodilator efficacy and safety of tiotropium in patients with moderate persistent asthma when administered 1.25µg, 2.5 µg and 5.0 µg tiotropium inhalation solution ex mouthpiece once daily in the evening.;Primary end point(s): Peak FEV1 response (within 3 hours post dosing). Efficacy will be evaluated based on PFT measurements over 3 hours: The primary efficacy variable will be forced expiratory volume in one second (FEV1). The primary efficacy endpoint is FEV1 Peak0-3 response determined at the end of each of the four 4-week treatment periods. FEV1 Peak0-3 is defined as the maximum FEV1 measured within the first 3 h post dosing. FEV1 Peak0-3 response is defined as the difference of FEV1 Peak0-3 and the FEV1 baseline measurement. Baseline is the pre-treatment FEV1 measured at visit 2 in the evening 10 minutes prior to administration of the first dose of study medication.;Timepoint(s) of evaluation of this end point: 4 weeks; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): FVC Peak0-3; trough FVC; trough FEV1; FEV1 (AUC0-3h); FVC (AUC0-3h); individual in-clinic FEV1/FVC/PEF measurements; home assessment: PEF a.m./p.m. (last weekly mean of treatment period); PEF variability; use of p.r.n. rescue medication; and night time awakenings; and in a subset of patients: FEV1 (AUC0-12h), FEV1 (AUC12-24h), FEV1 (AUC0-24h), FVC (AUC0-12h), FVC (AUC12-24h), FVC (AUC0-24h).;Timepoint(s) of evaluation of this end point: 1) to 6): 4 weeks; 7) and 8): last week of 4 week treatment; 9) and 10): 16 weeks; 11) to 16): 4 weeks; | — |
Countries
Austria, Germany, Ukraine
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed