E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this trial is to evaluate efficacy and safety of two doses (2.5 μg and 5 μg) of tiotropium inhalation solution administered once daily (in the evening) compared to placebo on top of maintenance therapy with low doses of inhaled corticosteroid controller medication in patients with mild persistent asthma. |
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E.2.2 | Secondary objectives of the trial |
1.Trough forced expiratory volume in one second (trough FEV1) response determined at the end of the 12-week treatment period. 2.Peak forced vital capacity response within 3 hours post dosingat the end of the 12-week treatment period. 3.FEV1 (AUC0-3h) and FVC (AUC0-3h) response at the end of the 12-week treatment period. 4.Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 12-week treatment period. 5.Use of prn rescue medication during the entire study period. 6.Time to first asthma and severe asthma exacerbation during the 12 week treatment period. Safety objectives include evaluation of: All adverse events,Lab tests,12-lead ECG., Vital signs, Physical examination. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 18 years or more at Visit 0 and 75 years or less at Visit 0. All patients must have 3. at least a 3 months history of asthma at the time of enrolment into the trial. The initial diagnosis of asthma must have been made before the patient's age of 40; 4. 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 FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%. 5. Patient's diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (within 10 minutes pre and 15-30 minutes after 400 μg salbutamol/albuterol) resulting in a FEV1 increase of ≥ 12% and ≥ 200mL. If this is not achieved the reversibility test may be repeated once within two weeks. 6. All patients must be symptomatic despite their current maintenance treatment with low doses of inhaled corticosteroids. 7. All patients must be symptomatic at Visit 1 (screening) and Visit 2 as defined by an ACQ mean score of ≥ 1.5. 8. All patients must have been on maintenance treatment with a low, stable dose of inhaled corticosteroids (see Appendix 10.3) (alone or in a fixed combination with a 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 and who have a smoking history of less than 10 pack years ((see Appendix 10.3 for calculation). 10. Patients must be able to use the Respimat® inhaler (Appendix 10.1) correctly. 11. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the e-Diary/peak flow meter (e-Diary-compliance of at least 80% is required; refer to Section 6.2.1 for instructions). 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).
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E.4 | Principal 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) 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 number 1. 3. Patients requiring more than 10 puffs of rescue medication (salbutamol/albuterol MDI) per 24 hours on 2 consecutive days during the screening period. 4. Patients with a recent history (i.e. six months or less) of Acute Coronary Syndrome (STEMI, Non-STEMI and Unstable Angina Pectoris). 5. Patients who have been hospitalised for cardiac failure during the past year. 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. 7. Patients with lung diseases other than asthma (e.g. 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. 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. 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 tiotropium inhalation solution. 14. Pregnant or nursing woman, 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) 16. 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. 17. 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 . 18. Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the screening period. 19. Patients who have been treated with systemic, i.e. oral or intravenous corticosteroids within four weeks prior to Visit 1 and/or during the screening period. 20. Patients who have been treated with depot corticosteroids within six months prior to Visit 1 and/or during the screening period. 21. Patients who have ever been treated with anti-IgE antibodies. 22. Patients who have been treated with leukotriene modifiers and systemic anticholinergics within two weeks prior to Visit 1 and/or during the screening period. 23. Patients who have been treated with inhaled long acting beta adrenergics within four weeks prior to Visit 0 and/or during the screening period 24. Patients who have been treated with long acting beta adrenergics combination products within four weeks prior to Visit 0 and/or during the screening period. 25. Patients who have been treated with cromolyn sodium or nedocromil sodium within two weeks prior to Visit 1 and/or during the screening period. 26. Patients who have been treated with methylxanthines or phophodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2). 27. Patients who have taken an investigational drug within four weeks or six half lives whichever is greater prior to Visit 1. 28. Patients who have been treated with other non-approved and according to international guidelines not recommended ’experimental’ drugs for routine asthma therapy (e.g. TNFalpha blockers, methotrexate, cyclosporin) within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2). 29. Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2). 30. Current participation in another trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be forced expiratory volume in one second (FEV1). The primary efficacy endpoint is the peak FEV1 response within 3 hours post dosing (FEV1 peak0-3h response) determined at the end of the 12-week treatment period. Peak FEV1 is defined as the maximum value of the FEV1 measurements within 3 hours post evening dosing. Peak FEV1 response is defined as the change from baseline in peak FEV1. Baseline is the pre-treatment FEV1 measured at Visit 2 in the evening 10 minutes prior to the evening dose of the patient's usual asthma medication (if usual posology) and the first dose of trial medication. The key secondary endpoint is the trough forced expiratory volume in one second (trough FEV1) response determined at the end of the 12-week treatment period.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is the last visit of the last patient undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |