A Phase II randomised, double-blind, placebo-controlled, incompletecrossover trial with 4-week treatment periods to evaluate efficacy andsafety of tiotropium inhalation solution (doses of 1.25µg, 2.5µg and 5µg) delivered via Respimat® inhaler once daily in the evening in adolescents(12 to 17 yrs old) with moderate persistent asthma

• Conditions: Moderate persistent asthma in adolescents (12 to 17 years old); MedDRA version: 12.1Level: LLTClassification code 10003555Term: Asthma bronchial

• Registration Number: EUCTR2009-017745-55-SI
• Lead Sponsor: Boehringer Ingelheim Pharma GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-09
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

1. All patients and parents (or legally accepted caregiver) 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 study procedures including medication washout and restrictions. A separate informed consent is required for pharmacogenomic sampling (consent for pharmacogenomic sampling is not a prerequisite for study entry).

2. Male or female patients between 12 and 17 years of age.

3. All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis must have been confirmed in the past and should be documented by at least one of the following criteria that were adapted from GINA 2008:
•an increased hyperresponsiveness to histamine, metacholine, mannitol or exercise challenge or
•a positive trial of glucocorticosteroids or a bronchodilator reversibility to a beta-2-adrenergic drug resulting in a FEV1 increase of =12% and 200 mL* or resulting in a PEF increase of =20% or
•a diurnal PEF variability of =10% (twice daily measurements) or =20% (more than 2 PEF assessments per day). Diurnal variability is defined as the amplitude (difference between maximum and minimum value for the day) expressed as percentage of the mean daily PEF value and averaged over 7 to 14 days or
•a bronchodilator reversibility to a beta-2-adrenergic drug resulting in a FEV1 increase of =12% and 200 mL* at Visit 1, as per inclusion criterion No.7
*please refer to inclusion criterion No.7 for exceptions

3. All patients must have a documented history of at least 3 months of asthma and fulfill the diagnostic criteria of moderate persistent asthma, according to the current GINA guidelines at the time of enrolment into the trial.

4. All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose (i.e., =400 µg to =800 µg budesonide or equivalent (see protocol table 3.3.1: 1), either as mono treatment or in combination with a LABA or leukotriene modifier for at least 4 weeks before Visit 1. While the LTRA is permitted throughout the trial, the LABA has to be stopped at least 24 hours prior to Visit 1, as no LABAs are permitted during the run-in and treatment periods of this trial.

5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an ACQ mean score of =1.5.

6. All patients must have a pre-bronchodilator FEV1 >60% and =90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ±30%.

7. All patients must have an increase in FEV1 of =12% and 200 mL 15 minutes after 400 µg salbutamol at Visit 1. If patients in the lower age range (e.g., 12 to 15 year olds) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (=12%) post-bronchodilator response.

8. All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.

9. Patients should be able to use the Respimat® inhaler correctly.

10. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres, according to ATS/ERS standards and the use of the electronic diary/peak flow meter.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of su

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 clinically relevant abnormal screening haematology or blood chemistry will be excluded if the abnormality defines a significant disease as defined in exclusion criterion 1. For participation in PK sampling, a haemoglobin of less than 12.5 g/dl for female patients and less than 13.5 g/dl for male patients will be regarded as exclusion criterion.

3. Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year.

4. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention (pacemaker implantation, catheter ablation etc.) or a change in drug therapy within the past year.

5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.

6. Patients with lung diseases other than asthma (e.g. CF). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia (BPD) will be regarded as exclusion criterion.

7. Patients with known active tuberculosis.

8. Patients with significant alcohol or drug abuse within the past two years.

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 who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).

11. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.

12. Pregnant or nursing adolescent female patients, including female patients with a positive ßHCG (serum pregnancy) testing at screening (Visit 1).

13. Sexually active female patients of child-bearing 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).
Note: sexual abstinence is deemed to be a highly effective contraception method.

14. Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.

15. Patients who have been treated with long-acting anticholinergics (e. g. tiotropium - Spiriva®) within 4 weeks prior to screening (Visit 1).

16. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.

17. Patients who have been treated with Anti-IgE treatment (Omalizumab –Xolair®) within the last 6 months prior to screening.

18. Patients who are being treated with beta-blocker medication. Topical cardio-selective beta-blocker eye medications for treatment of non-narrow angle glaucoma are allowed.

19. Patients who have been treated with systemic (oral or i.v.) corticosteroids within 4 weeks prior to screening (Visit 1).

20. Patients who have been treated with long-acting theophylline preparations within 2 weeks prior to screening (Visit 1) or during the run-in period.

21. Patients who

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified