Asthma
Conditions
Brief summary
To establish that at least one of the two doses of Budesonide, as an ethanolic solution inhaled from the Respimat ® inhaler (100 and 200 mcg, 2 puffs bid) for a 12-week study period in symptomatic moderate to severe asthmatic patients, gives a therapeutic response, which is not inferior to that obtained from the dose of Budesonide inhaled from the Turbohaler ® (200 mcg, 2 puffs bid) and that the safety profile is at least as good
Interventions
DRUGRespimat® Budesonide low dose
DRUGRespimat® Budesonide high dose
DRUGTurbohaler® Budesonide
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients of either sex aged 18 - 65 years (inclusive) * Non-smokers or ex smokers. HAVING stopped smoking \>= 1 year prior to screening and with a smoking history of \<= 10 pack years * Diagnosis of MODERATE to SEVERE bronchial asthma with a duration of at least 6 months with the inclusion criteria 4 plus 5 and a diagnosis of asthma according to the WHO guidelines for at least one year * Increase of asthma symptoms (wheeze, cough, shortness of breath, chest tightness) when exposure to any of the following stimuli: cold, dry air, dust, smoke, exercise and allergens * Patients on a stable dosage of either * 800 mcg \<= BDP (beclomethasone dipropionate) \<= 1600 mcg daily or other inhaled steroid with or without inhaled long acting β2-agonists or oral xanthines at screening visit 1 for the past 4 weeks and short acting β2-agonists prn for the past 6 weeks or * 400 mcg \<= BDP \< 800 mcg daily or other inhaled steroid and inhaled long-acting β2-agonists (or oral xanthines), at screening visit 1 for the past 4 weeks and short acting β2-agonists prn for the past 6 weeks * FEV1 \>= 60% but \<= 90 % predicted normal at visit 1 after withholding respiratory drugs as per section 4.2.1. Predicted normal values are based on the guidelines for standardized function testing of the European Community for Coal and Steel (ECCS) * Males: FEV1 pred. (L) = 4.30 x Height (m) - 0.029 x Age (yrs) - 2.49 * Females: FEV1 pred. (L) = 3.95 x Height (m) - 0025 x Age (yrs) - 2.60 * Patient must demonstrate an improvement in FEV 1 \>= 12% above baseline and an absolute change of at least 200 ml within 30 minutes after administration of two puffs of salbutamol MDI (metered dose inhaler) (100 mcg per puff). Historical data within the previous 6 months are acceptable * Patients must be able to be trained in the proper use of MDI, Turbohaler® and Respimat® and to perform technically satisfactory pulmonary function tests * Patients must be willing and be able to give informed written consent prior to participation in the trial i.e. prior to pre-study wash-out of their usual pulmonary medications and are willing and able to complete the entire study as described in the protocol
Exclusion criteria
* Patients with a history of seasonal exacerbation of asthma suggesting seasonal asthma which would not be controlled by medication allowed in the protocol (see 4.2.2) and likely to occur during the time period that the patients will be in the study * History of cardiovascular, renal, neurologic, liver, immunologic or endocrine dysfunction if they are clinically significant. A clinically significant disease is defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study * Patients with a recent history (\<= 1 year) of myocardial infarction and/or (\<= 3 years) of heart failure or patients with any cardiac arrhythmia requiring drug therapy * History of cancer within the past 5 years excluding treated basal cell carcinoma * Patients with current psychiatric disorders which would interfere with the conduct of the trial * Patients with history or presence of glaucoma and/or posterior subcapsular cataracts * Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in mean weekly morning pre-dose Peak Expiratory Flow Rate (a.m. PEFR) | Day1, 15, 29, 43, 57, 71, 85 (before intake of inhaled medication) |
Secondary
| Measure | Time frame |
|---|---|
| Change in Forced Vital Capacity (FVC) | Baseline, Day1, 15, 29, 43, 57, 71, 85 |
| Change in Peak Expiratory Flow Rate (PEFR) | Baseline, Day1, 15, 29, 43, 57, 71, 85 |
| Changes in Mean weekly evening pre-dose PEFR (p.m. PEFR) | Day1, 15, 29, 43, 57, 71, 85 (before intake of inhaled medication) |
| Daily puffs of β2-agonists usage | up to 85 days |
| Diurnal and nocturnal asthma symptom score | up to 85 days |
| Symptoms free days and/or nights | up to 85 days |
| Withdrawal due to moderate or severe asthma exacerbation | up to 85 days |
| Change in Forced expiratory flow at 25-75% of vital capacity (FEF 25-75%) | Baseline, Day1, 15, 29, 43, 57, 71, 85 |
| Change in systolic blood pressure | Baseline, Day1, 15, 29, 43, 57, 71, 85 |
| Change in pulse rate | Baseline, Day1, 15, 29, 43, 57, 71, 85 |
| Change from baseline in 12-lead electrocardiogram (ECG) | Baseline, Day 85 |
| Changes from baseline in laboratory parameters | Baseline, Day 85 |
| Occurence of adverse events | up to 85 days |
| Change in Forced Expiratory Volume in one second (FEV1) | Baseline, Day1, 15, 29, 43, 57, 71, 85 |
| Markers of bone formation - Plasma osteocalcin levels (sub-group of patients) | Day 1, Day 85 |
| Markers of bone formation - Bone alkaline phosphatase (sub-group of patients) | Day 1, Day 85 |
| Markers of bone formation - serum calcium (all study population) | Day 1, Day 85 |
| Markers of bone formation - serum phosphate (all study population) | Day 1, Day 85 |
| Markers of bone formation - serum procollagen I (sub-group of patients) | Day 1, Day 85 |
| Markers of bone dissolution - Urine deoxypyridiline (subset of patients) | Day 1, Day 85 |
| Serum cortisol levels (a.m.) - (subset of study population) | Day 1, 29, 57, 85 |
| 10 hour urinary free cortisol/creatinine ratio (subset of study population) | Day 1, 29, 57, 85 |
| Oral Candidiasis (quantitative assessment) | up to 85 days |
| Incidence of hoarseness of voice | up to 85 days |
| Incidence of sore throat | up to 85 days |
| Markers of bone formation - Alkaline phosphatase (all study population) | Day1, Day 85 |
| Incidence of administration related bronchoconstriction at first and last dose | Day 1, Day 85 |
Outcome results
None listed