patients of either sex, 12 to 17 years old, with a diagnosis of severe persistent asthma MedDRA version: 14.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Boehringer Ingelheim RCV GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. All patients and their parent(s) (or legally accepted representative) must sign and date respectively an informed assent and an informed consent consistent with ICH GCP guidelines and local legislation prior to the patient’s participation in the trial, i.e. prior to any study procedures including medication wash-out and restrictions. A separate informed consent/assent is required for pharmacogenomic sampling (consent/assent for pharmacogenomic sampling is not a prerequisite for study entry). 2. Male or female patients between 12 and 17 years of age (at date of informed consent/assent). 3. All patients must have at least a 3-month history of asthma at the time of enrolment into the trial. 4. All patients must have been on maintenance treatment with an inhaled corticosteroid either at stable high dose in combination with another controller medication (e.g. a LABA or a leukotriene modifier), OR at stable medium dose in combination with two other controller medications (e.g. a LABA and/or a leukotriene modifier and/or a sustained release theophylline), for at least 4 weeks before Visit 1).For the lower age group (i.e. 12 to 14 year old patients) the inhaled corticosteroid dosing recommendations for “children older than 5 years” may be appropriate. 5. All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an ACQ 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 at Visit 2, the patient’s Visit 2 can be repeated once for further assessment (see Section 6.1 for details on visit rescheduling). 6. All patients must have a pre-bronchodilator FEV1 = 60% and = 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to Wang et al.. 7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%. 8. All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of = 12% and = 200 mL 15 to 30 minutes after 400 µg salbutamol (albuterol). If patients in the lower age range (e.g. 12 to 14 year old patients) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (=12%) post-bronchodilator response. 9. All patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment. 10. Patients must be able to use the Respimat® inhaler correctly. 11. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres according to ATS/ERS standards and use of the electronic diary/peak flow meter (diary compliance of at least 80% is required). Are the trial subjects under 18? yes Number of subjects for this age range: 375 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with a significant disease other than asthma (e.g. cystic fibrosis). 2. Patients with a clinically relevant abnormal haematology or blood chemistry at screening (Visit 1), if the abnormality defines a significant disease as defined in exclusion criterion No. 1. 3. Patients with a history of congenital or acquired heart disease, and/or who 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 (e.g. pacemaker implantation) 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 known active tuberculosis. 7. Patients with significant (in the opinion of the investigator) alcohol or drug abuse within the past two years. 8. Patients who have undergone thoracotomy with pulmonary resection. 9. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to Visit 1. 10. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the study medication delivery system. 11. Pregnant or nursing adolescent female patients, including female patients with a positive ß-HCG (serum pregnancy) testing at Visit 1. 12. Female patients of child-bearing potential not using a highly effective method of birth control. 13. Patients who have taken an investigational drug within four weeks or six half lives (whichever is greater) prior to Visit 1. 14. Patients who have been treated with long-acting inhaled anticholinergics (e.g. tiotropium - Spiriva®) or systemic anticholinergic treatment such as spasmolytics within four weeks prior to Visit 1 and/or during the screening period (between Visit 1 and Visit 2). 15. Patients who have been treated with systemic (oral or intravenous) corticosteroids at a high dose (prednisolone or prednisolone equivalent > 5mg/day or > 10 mg every second day) or at a not stable low dose (prednisolone or prednisolone equivalent < 5mg/day or < 10 mg every second day) within four weeks prior to Visit 1 and/or during the screening period (between Visit 1 and Visit 2). 16. Patients who have been treated with leukotriene modifiers if not stabilised for at least four weeks prior to Visit 1 or during the screening period (between Visit 1 and Visit 2). 17. Patients who have been treated with long-acting theophylline preparations if not stabilised for at least two weeks prior to Visit 1 or during the screening period (between Visit 1 and Visit 2). 18. Patients who have been treated with anti-IgE treatment (e.g. omalizumab - Xolair®) if not stabilised for at least six months prior to Visit 1 or during the screening period (between Visit 1 and Visit 2). 19. Patients who have been treated with cromones (e.g. sodium cromoglycate and nedocromil sodium) if not stabilised within four weeks prior to Visit 1 and/or during the screening period (between Visit 1 and Visit 2). 20. Patients who have been treated with oral beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period (between Visit 1 and Visit 2). 21. Patients who have been treated with systemic oral or i.v. or s.c. beta-adrenergics within four weeks prior to Visit 1 and/or during the screening period (between Visit 1 and Visit 2).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 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 highest FEV1 reading observed within 3 hours after administration of the evening dose of each randomised treatment. 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 regular posology) and first dose of trial medication. ;Main Objective: The primary objective of the trial is to demonstrate superiority of tiotropium (5 µg and possibly 2.5 µg once daily in the evening) over placebo with regard to the primary pulmonary function endpoint after 12 weeks of treatment.;Secondary Objective: Secondary objectives are to evaluate efficacy of tiotropium with regard to other endpoints, and to evaluate the safety of tiotropium, compared to placebo, as add-on controller therapy on top of usual care in this patient population.;Timepoint(s) of evaluation of this end point: 12 weeks after start of treatment with IMP | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Change from baseline at the end of the 12-week treatment period in the trough forced expiratory volume in one second (trough FEV1 response). 2.Change from baseline at the end of the 12-week treatment period in the highest forced vital capacity reading observed within 3 hours after administration of the evening dose of each randomised treatment. 3.Change from baseline at the end of the 12-week treatment period in the area under the curve from zero to 3 hours of the trough forced expiratory volume and the forced vital capacity. 4.The number of responders (improvement of at least 0.5 for the ACQ) as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 12-week treatment period. 5.Number of inhalations of salbutamol (albuterol) rescue medication used per day during the 12-week treatment period. 6.Time to first severe asthma exacerbation during the 12-week treatment period. 7.Time to first asthma exacerbation during the 12-week treatment period. 8.All adverse events;Timepoint(s) of evaluation of this end point: 1-5.12 weeks after start of treatment with IMP. 6-7.First occurrence since start of treatment with IMP within 12 weeks. 8.12 weeks after start of treatment with IMP. | — |
Countries
Argentina, Australia, Bulgaria, Germany, Guatemala, Hungary, Israel, Italy, Latvia, Mexico, Norway, Philippines, Portugal, South Africa, Ukraine, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed