E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate persistent asthma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 |
Demonstrate 24 hour bronchodilator efficacy and safety of tiotropium 5 μg administered once daily (in the evening) delivered by the Respimat® inhaler for four weeks in comparison to placebo. Evaluate efficacy and safety of tiotropium 2.5 μg administered twice daily delivered by the Respimat® inhaler for four weeks in comparison to placebo and to tiotropium 5 μg administered once daily (in the evening) delivered by the Respimat® inhaler for four weeks in patients with moderate persistent asthma. |
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E.2.2 | Secondary objectives of the trial |
The effect on asthma control, nighttime awakenings and rescue medication use will be evaluated. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Outpatients with a history of asthma and a current diagnosis of moderate persistent asthma (according to GINA guideline) are eligible for inclusion if they fulfil all the inclusion criteria and none of the exclusion 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 at least 18 years but not more than 75 years. 3. All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 minutes after 400 μg salbutamol) resulting in a FEV1 increase of ≥ 12% and ≥ 200mL. 4. The initial diagnosis of asthma must have been made before the patient's age of 40. 5. All patients must have a diagnosis of moderate persistent asthma and must be symptomatic despite their current maintenance treatment with medium doses of inhaled corticosteroids. 6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (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 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 atVisit 2, the patient’s Visit 2 can be repeated once for further assessment 8. 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]. 9. All patients must have an increase in FEV1 of ≥ 12% and ≥ 200 mL 15 minutes after 400 μg salbutamol at Visit 1. NOTE: If this is not achieved the reversibility test may be repeated once within two weeks. 10. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%. 11. 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. 12. Patients must be able to use the Respimat® inhaler (Appendix 10.1) correctly. 13. 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-Diarycompliance of at least 80% is required; refer to Section 6.2.1 for instructions). 14. 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) 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 if the abnormalitiy defines a significant disease as defined in exclusion criterion no. 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 significant alcohol or drug abuse within the past two years. 11. 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). 12. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the study medication delivery systems. 13. Pregnant or nursing women. 14. 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 are accepted if condom or occlusive cap are 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. 15. Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 or during the screening period. Topical cardio-selective beta-blocker eye medications for non-arrow angle glaucoma are allowed. 16. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 or during the screening period. 17. Patients who have been treated with oral beta-adrenergics within four weeks prior to Visit 1 or during the screening period. 18. Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 or during the screening period. 19. Patients who have been treated with anti-IgE antibodies, e.g. omalizumab (Xolair®), within 6 months prior to Visit 1 or during the screening period. 20. Patients who have been treated with cromolyn sodium or nedocromil sodium within two weeks prior to Visit 1 or during the screening period. 21. Patients who have been treated with methylxanthines within two weeks prior to Visit 1 or during the screening period. 22. Patients who have taken an investigational drug within four weeks prior to Visit 1. 23. 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 or during the screening period. 24. 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. 25. Patients who have previously been randomised in this trial or are currently participating in another trial. 26. Patients who have been treated with depot corticosteroids within six months prior to Visit 1 or during the screening period. 27. Patients who have been treated with leukotriene modifiers within two weeks prior to Visit 1 or during the screening period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be the forced expiratory volume in one second (FEV1). The primary endpoint is the FEV1 area under the curve (AUC) 0-24 hours (AUC0-24h) (L) determined at the end of each 4 week treatment period. All measurements will be performed in relation to evening (p.m.) dosing |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |