A Phase II, randomised, double- blind, placebo controlled, cross-overefficacy and safety comparison of tiotropium 5 µg administered oncedaily (in the evening) and tiotropium 2.5 µg administered twice dailydelivered by the Respimat® inhaler for four weeks versus placebo inpatients with moderate persistent asthma

Conditions: moderate persistent asthma
MedDRA version: 12.1Level: LLTClassification code 10003553Term: Asthma

Registration Number: EUCTR2009-018006-21-AT

Lead Sponsor: Boehringer Ingelheim RCV GmbH & CoKG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 90

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).
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 d

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Demonstrate 24 hour bronchodilator efficacy and safety of tiotropium 5 µg<br>administered once daily (in the evening) delivered by the Respimat® inhaler for four<br>weeks in comparison to placebo. Evaluate efficacy and safety of tiotropium 2.5 µg<br>administered twice daily delivered by the Respimat® inhaler for four weeks in<br>comparison to placebo and to tiotropium 5 µg administered once daily (in the<br>evening) delivered by the Respimat® inhaler for four weeks in patients with moderate persistent asthma.;Secondary Objective: The effect on asthma control, nighttime awakenings and rescue medication use will be evaluated.;Primary end point(s): The primary efficacy variable will be the forced expiratory volume in one second (FEV1).<br>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

Secondary Outcome Measures