MedDRA version: 14.1 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 100000004855
Conditions
Sponsors
Boehringer Ingelheim RCV 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 2. Male or female patients aged at least 18 years at Visit 0 but not more than 75 years at Visit 0. Diagnosis 3. All patients must have at least a 3 months history of asthma at the time of enrolment (signing ICF) into the trial. The initial diagnosis of asthma must have been made before the patient's age of 40. If the patient is > 40 years and the diagnosis has not yet been recorded in the patient's medical files, the investigator should assess whether the patient's medical history 4. All patients must have a pre-bronchodilator FEV1 = 60% predicted and = 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to ECSC [R94-1408] (see Appendix 10.3). Variation of absolute pre-bronchodilator FEV1 values at Visit 1 and Visit 2 (randomisation visit) must be within ± 30%. 5. Patient’s diagnosis of asthma has to be confirmed at Visit 1 with bronchodilator reversibility (ie 10 minutes prior to and 15-30 minutes after inhalation of 400 µg salbutamol) defined as an FEV1 increase of = 12% and = 200 mL. NOTE: If this is not achieved at the screening visit the reversibility test including ACQ may be repeated once within two weeks. Symptoms 6. All patients must have a diagnosis of moderate persistent asthma and must be symptomatic despite their current maintenance treatment with medium doses of ICS. 7. All patients must be symptomatic at Visit 1 (screening visit) and Visit 2 (randomisation visit) as defined by an ACQ mean score of = 1.5. 8. All patients must have maintenance treatment with stable medium daily dose of ICS (alone or in a fixed-dose combination with a LABA or SABA) for at least 4 weeks prior to Visit 1. 9. 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 at Visit 0. 10. Patients must be able to use the Respimat® inhaler correctly. 11. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the AM3® (e-diary) compliance of at least 80% is required. 12. Patients taking a chronic pulmonary medication allowed by the study protocol must be willing to continue this therapy for the entire duration of the study (exception: times of acute disease deterioration). 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 82 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
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 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 hematology or blood chemistry at Visit 1 if the abnormality defines a significant disease as defined in exclusion criterion no. 1. 3. Patients requiring more than 12 puffs of rescue medication (salbutamol MDI) per 24 hours for more than 2 consecutive days between Visit 1 and Visit 2 (screening period). 4. Patients with a recent history (ie six months or less) of Acute Coronary Syndrome (STEMI, non-STEMI, Unstable Angina Pectoris) prior to Visit 1 (screening). 5. Patients who have been hospitalised for cardiac failure during the past year prior to Visit 1 (screening). 6. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year prior to Visit 1 (screening). 7. Patients with lung diseases other than asthma (eg COPD). 8. Patients with known active tuberculosis. 9. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years prior to Visit 1 (screening). Patients with treated basal cell carcinoma are allowed. 10. 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. 11. Patients with significant alcohol or drug abuse on Investigator’s assessment within the past two years prior to Visit 1 (screening). 12. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening). 13. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the study medication delivery systems. 14. Pregnant or nursing women, including female patients with positive ß-HCG test at Visit 1. 15. Female patients of child-bearing potential not using highly effective method of birth control. As defined in ICH (M3) [R09-1400], note 3, highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (ie less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner. Barrier contraceptives (eg male condom or diaphragm) are acceptable if used in combination with spermicides (eg 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. 16. Patients who have been treated with restricted medication (refer to Table 4.2.2.1) prior to Visit 1 and/or during the screening period. 17. Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period. Visit 1 and/or Visit 2 should be postponed in case of an asthma exacerbation or respiratory tract infection. Refer to Section 6.1 for information on re-scheduling of visits. 18. Pat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the 24-hour FEV1-profile of tiotropium solution for inhalation after 4 weeks treatment periods of 5 µg tiotropium administered once daily in the evening and 2.5 µg tiotropium administered twice daily (morning and evening) with the Respimat inhaler. In addition, in a subset of patients the pharmacokinetics of tiotropium in patients with asthma will be characterized. The objective of the pharmacokinetic subinvestigation is to compare the 24 hours pharmacokinetic profile of 5 µg tiotropium administered once daily and 2.5µg tiotropium administered twice daily. ;Secondary Objective: Not Applicable;Primary end point(s): The primary efficacy variable will be the forced expiratory volume in one second (FEV1). The primary endpoint is the FEV1 AUC0-24h (L) response determined at the end of each 4-week randomised treatment period. The FEV1 AUC0-24h is defined as the mean FEV1 over the 24-hour observation period (0-24 h) normalized for time after inhalation of the last evening dose of study medication. The mean FEV1 will be calculated as area under the curve from zero time to 24 hours, using the trapezoidal rule divided by the corresponding duration (ie 24 hours) to give the result in litres. The pre-dose FEV1 measurement obtained at the end of each 4-week treatment period prior to inhalation of the last evening dose of study medication will be assigned to zero time. Value recorded at 11h 50min and at 23h 50min post dosing will be assigned to 12 and 24 hours, respectively. FEV1 AUC0-24h response is defined as the change of FEV1 AUC0-24h from the baseline FEV1 value, which is the measurement obtained on Visit 2 (randomisation visit) prior to the first evening dose of randomised study medication. ;Timepoint(s) of evaluation of this end point: At the end of each 4-week randomised treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. FEV1 AUC0-12h (L) response determined at the end of each 4-week period of randomised treatment. 2. FEV1 AUC12-24h (L) response determined at the end of each 4-week period of randomised treatment. FEV1 AUC over the first 12 hours (0-12 h) and the second 12 hours will be calculated similar to FEV1 AUC0-24h. AUC0-12h and AUC12-24h responses will be calculated similar to FEV1 AUC0-24h response. 3. Peak FEV1 (L) response, determined at the end of each 4-week period of randomised treatment, is defined as the highest FEV1 reading observed within the 24-hour period following inhalation of the last evening dose of study medication. 4. Trough FEV1 (L) response, determined at the end of each 4-week period of randomised treatment, is defined as the FEV1 value just prior to the last evening dose of study medication. 5. Forced vital capacity (FVC) AUC0-24h response determined at the end of each 4-week period of randomised treatment. 6. FVC AUC0-12h response (L) determined at the end of each 4-week period of randomised treatment. 7. FVC AUC12-24h response (L) determined at the end of each 4-week period of randomised treatment. 8. Peak FVC (L) response determined at the end of each 4-week period of randomised treatment. 9. Trough FVC (L) responses determined at the end of each 4-week period of randomised treatment. AUC0-12h, AUC12-24h, AUC0-24h, trough and peak FVC responses will be calculated similar to FEV1 response endpoints. 10. Peak expiratory flow (PEF) AUC0-24h (L/min) response determined at the end of each 4-week period of randomised treatment. PEF AUC0-24h response will be calculated similar to FEV1 AUC0-24h response. ;Timepoint(s) of evaluation of this end point: At the end of each 4-week randomised treatment period. | — |
Countries
Austria, Germany, Hungary, Slovenia
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed