Health Condition 1: null- Moderate persistent Asthma
Conditions
Interventions
Intervention1: Tiotropium Inhalation solution: 5 mcg once daily
Intervention2: Tiotropium Inhalation solution: 2.5 mcg once daily
Control Intervention1: salmeterol (Active Comparator): 50 mcg twice da
Sponsors
Boehringer Ingelheim
Pfizer
Eligibility
Inclusion criteria
Inclusion criteria: 1. All patients must sign and date an Informed Consent Form 2. Male or female patients aged at least 18 years but not more than 75 years. 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 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 minutes after 400 mcg salbutamol (albuterol)) resulting in a Forced Expiratory Volume in one second (FEV1) increase of at least 12% and at least 200mL. 6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids for at least for 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 Asthma Control Questionnaire (ACQ) mean score of at least 1.5. 7. All patients must have a pre-bronchodilator FEV1 at least 60% and less than or equal to 90% of predicted normal at Visit 1. 8. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%. 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.
Exclusion criteria
Exclusion criteria: 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 patients ability to participate in the trial. 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. Patients with a recent history (i.e. six months or less) of myocardial infarction. Patients who have been hospitalised for cardiac failure during the past year. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year. Patients with lung diseases other than asthma (e.g. Chronic Obstructive Pulmonary Disease (COPD)). Patients with known active tuberculosis. 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. 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. Patients with significant alcohol or drug abuse within the past two years. 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). Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediamineteraacetic acid (EDTA), salmeterol xinafoate or any other components of the study medication delivery systems. Pregnant or nursing woman. Women of childbearing potential not using a highly effective method of birth control. Patients who have taken an investigational drug within four weeks prior to Visit 1. Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period. Topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 and/or during the screening period. Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period. Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 and/or during the screening period. Patients who have been treated with anti-IgE antibodies, e.g. omalizumab (Xolair®), within 6 months prior to Visit 1 and/or during the screening period. Patients who have been treated with cromone within two weeks prior to Visit 1 and/or during the screening period. Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period. Patients who have been treated with other non-approved and according to international guidelines not recommended "experimental" drugs for routine asthma therapy within four weeks prior to Visit 1 and/or during the screening period. <br/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak forced expiratory volume in one second (FEV1) response (within 3 hours post dosing)Timepoint: 24 weeks;The responder as assessed by the Asthma Control Questionnaire (ACQ) (on combined data from the two twin trials 205.418 and 205.419Timepoint: 24 weeks;Trough FEV1 responseTimepoint: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| All adverse eventsTimepoint: Day 0 until end of follow up (31 weeks);Asthma symptom free daysTimepoint: all days during 24 weeks of treatment;Asthma symptoms as assessed by the patient's electronic diaryTimepoint: all days during 24 weeks of treatment;FEV1 (Area Under the Curve; AUC0-12h), FEV1 (AUC12-24h), FEV1 (AUC0-24h), FVC (AUC0-12h), FVC (AUC12-24h) and FVC (AUC0-24h)Timepoint: 24 weeks;FEV1 (Area Under the Curve; AUC0-3h) and FVC (AUC0-3h)Timepoint: 24 weeks;health care resource utilisation (HCRU)Timepoint: 4, 8, 16 and 24 weeks;Individual in-clinic FEV1, Forced Vital Capacity (FVC) and Peak Expiratory Flow (PEF) measurements at all time-points including peak, trough and AUC0-3hTimepoint: 0, 4, 8, 16 and 24 weeks;Peak (within 3 hours post dosing) and trough forced vital capacity (FVC).Timepoint: 24 weeks;PEF am/pm: change from baseline in mean weekly pre-dose morning and evening PEF measured by patients at homeTimepoint: 24 weeks;Quality of Life (EQ-5D)Timepoint: 4, 8, 16 and 24 weeks;Quality of Life as assessed by standardised Asthma Quality of Life Questionnaire (AQLQ (S))Timepoint: 4, 8, 16 and 24 weeks;The ACQ value (on combined data from the two twin trials 205.418 and 205.419)Timepoint: 4, 8, 16 and 24 weeks;The responder as assessed by the ACQ questionnaire for each twin trial separatelyTimepoint: 24 weeks;The responder as assessed by the Asthma Control Questionnaire (ACQ) (on combined data from the two twin trials 205.418 and 205.419Timepoint: 24 weeks;Time from dosing to maximum tiotropium plasma concentration (tmax)Timepoint: Day 1;Time to first asthma exacerbation (on combined data from the two twin trials 205.418 and 205.419)Timepoint: 24 weeks;Time to first severe asthma exacerbation (on combined data from the two twin trials 205.418 and 205.419)Timepoint: 24 weeks;Use of PRN salbutamol (albuterol) rescue medicationTimepoint: 24 weeks;Vital signs until 3 hours post-doseTimepoint: 0, 4, 8, 16 and 24 weeks;Vital status information (dead or ali | — |
Countries
Argentina, Austria, Brazil, China, Germany, India, Japan, Mexico, Poland
Contacts
Public ContactPartha Gokhale
Boehringer Ingelheim India Pvt. Ltd.
Outcome results
None listed