Safety and Efficacy of Berodual® Respimat® Compared to Berodual® MDI (Metered Dose Inhaler) in Asthma Patients
Primary Purpose
Asthma
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Berodual® via Respimat®, high dose
Berodual® via Respimat®, low dose
Berodual® via MDI, high dose
Placebo Respimat®
Placebo MDI
Sponsored by

About this trial
This is an interventional treatment trial for Asthma
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of bronchial asthma according to the ATS (American Thoracic Society)
- Age: 18 - 65 years
- Screening FEV1: 40 - 80 % of predicted normal. Predicted normal values will be based on the guidelines for standardised function testing of the European Community for Coal and Steel
- Airway obstruction reversibility: increase in FEV1 12% from baseline and ≥ 200 ml from baseline at 30 minutes after 2 puffs of Berodual® MDI
- Current non-smoker or ex-smoker (with a smoking history of ≤ 10 pack-years) with cessation of smoking ≥ 1 year prior to the screening visit
- Male or female patients
- Ability to be trained in proper use of MDI and RESPIMAT® devices
- Ability to perform technically satisfactory pulmonary function tests
- No hospital admission for an exacerbation and stable dosage of all pulmonary medication in the last four weeks (except for long acting β2 agonists)
- Willingness and ability to sign informed consent form prior to participation in the trial
Exclusion Criteria:
- Patients with significant disease other than asthma, e.g. history of clinically significant cardiovascular, renal, neurological, hepatic or endocrine dysfunction. A clinically significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or which may influence the results of the study or the ability of the patient to participate in and complete the study
- History of myocardial infarction within the last year
- Tuberculosis with indication for treatment
- History of cancer within the last five years, excluding treated basal cell carcinoma
- Patients who have undergone thoracotomy for pulmonary resection of more than one bullae, or with subsequent impaired thoracic muscle performance leading to unsatisfactory lung function testing
- Current psychiatric disorders
- History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
- An upper or lower respiratory tract infection in the four weeks prior to the screening visit (= Visit 1) or during the 2-week run-in period
- Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion
- Patients with AST/ALT (aspartate amino transferase/alanine amino transferase) (SGOT/SGPT (serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase)) > 200%, bilirubin > 150% (except isolated bilirubin increase due to Gilbert's Syndrome), or creatinine > 125% of the upper limit of the normal range
- Intolerance to aerosolised fenoterol- or ipratropium-containing products, and/or hypersensitivity to any of the MDI ingredients
- Patients using oral corticosteroid medication at unstable (i.e. less than 4 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg prednisone per day or 20 mg every other day
- Beta-blocker medication
- Patients who have taken an investigational drug one month or six half-lives (whichever is greater) prior to the screening visit
- History of drug abuse and/or alcoholism
- Pregnant or nursing women and women of childbearing potential or less than 2 years postmenopausal, who are not using medically approved means of contraception (oral contraceptives, intra-uterine devices or surgical Sterilisation)
- Previous participation in this study
- Patients who need more than 8 puffs of salbutamol (100 µg per puff) rescue medication on 3 or more consecutive days during the run-in period
- Severe bronchial asthma with frequent nocturnal asthma attacks or acute exacerbations induced by recurrent bronchial infections several times per year
- Patients with known hypersensitivity to anticholinergic drugs
- Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
- Patients with known narrow-angle glaucoma
- Patients who did not fill in at least 80% of the diary in the run-in period for both, medication taken and peak expiratory flow rate (PEFR) measurements are considered not compliant
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Active Comparator
Placebo Comparator
Placebo Comparator
Arm Label
Berodual® via Respimat®, high dose
Berodual® via Respimat®, low dose
Berodual® via MDI, high dose
Placebo via Respimat®
Placebo via MDI
Arm Description
Outcomes
Primary Outcome Measures
Change in average FEV1 (Forced expiratory volume in one second) (AUC0-6 (Area under the curve))
Secondary Outcome Measures
FEV1max
Time to onset of therapeutic response
Duration of therapeutic response
Time to peak FEV1
Change in averaged weekly morning and evening pre-dose PEFR (peak expiratory flow rate)
Extent of use of rescue medication
Change in night-time and daytime symptom scores
Overall incidence of adverse events
Number of patients with clinically significant changes in Heart rate
Number of patients with clinically significant changes in Blood pressure
Number of patients with clinically significant changes from baseline in laboratory investigations
Incidence of paradoxical bronchoconstriction
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02182479
Brief Title
Safety and Efficacy of Berodual® Respimat® Compared to Berodual® MDI (Metered Dose Inhaler) in Asthma Patients
Official Title
Comparison of the Safety and Efficacy of Berodual® Administered Via Respimat® Device (50 µg Fenoterol Hydrobromide/20 µg Ipratropium Bromide and 25 µg Fenoterol Hydrobromide/10 µg Ipratropium Bromide, 1 Puff q.i.d.) With That Administered Via the MDI (50 µg Fenoterol Hydrobromide/21 µg Ipratropium Bromide, 2 Puffs q.i.d.) in Asthma Patients Over a 12-week Period
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
April 1998 (undefined)
Primary Completion Date
June 1999 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
Study to demonstrate that at least one of the two doses of Berodual® (50 µg fenoterol hydrobromide/20 µg ipratropium bromide and 25 µg fenoterol hydrobromide/10 µg ipratropium bromide, 1 puff q.i.d.) administered via Respimat® gives a bronchodilator response which is not inferior to that obtained from one dose of Berodual® (50 µg fenoterol hydrobromide/21 µg ipratropium bromide, 2 puffs q.i.d.) administered via MDI and that the safety profile is at least as good in asthma patients treated for 12 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
631 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Berodual® via Respimat®, high dose
Arm Type
Experimental
Arm Title
Berodual® via Respimat®, low dose
Arm Type
Experimental
Arm Title
Berodual® via MDI, high dose
Arm Type
Active Comparator
Arm Title
Placebo via Respimat®
Arm Type
Placebo Comparator
Arm Title
Placebo via MDI
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Berodual® via Respimat®, high dose
Intervention Type
Drug
Intervention Name(s)
Berodual® via Respimat®, low dose
Intervention Type
Drug
Intervention Name(s)
Berodual® via MDI, high dose
Intervention Type
Drug
Intervention Name(s)
Placebo Respimat®
Intervention Type
Drug
Intervention Name(s)
Placebo MDI
Primary Outcome Measure Information:
Title
Change in average FEV1 (Forced expiratory volume in one second) (AUC0-6 (Area under the curve))
Time Frame
Pre-dose and 5, 15, 30, 60, 90, 120, 180, 240, 300, 360 minutes post-dose on day 1, 29, 57 and 85
Secondary Outcome Measure Information:
Title
FEV1max
Time Frame
Pre-dose and 5, 15, 30, 60, 90, 120, 180, 240, 300, 360 minutes post-dose on day 1, 29, 57 and 85
Title
Time to onset of therapeutic response
Time Frame
Days 1, 29, 57 and 85
Title
Duration of therapeutic response
Time Frame
Days 1, 29, 57 and 85
Title
Time to peak FEV1
Time Frame
Pre-dose and 5, 15, 30, 60, 90, 120, 180, 240, 300, 360 minutes post-dose on days 1, 29, 57 and 85
Title
Change in averaged weekly morning and evening pre-dose PEFR (peak expiratory flow rate)
Time Frame
up to day 85
Title
Extent of use of rescue medication
Time Frame
up to day 85
Title
Change in night-time and daytime symptom scores
Time Frame
up to day 85
Title
Overall incidence of adverse events
Time Frame
up to day 85
Title
Number of patients with clinically significant changes in Heart rate
Time Frame
Pre-dose and 15, 30, 60, 90, 120, 180, 240, 300, 360 minutes post-dose on days 1, 29, 57 and 85
Title
Number of patients with clinically significant changes in Blood pressure
Time Frame
Pre-dose and 15, 30, 60, 90, 120, 180, 240, 300, 360 minutes post-dose on days 1, 29, 57 and 85
Title
Number of patients with clinically significant changes from baseline in laboratory investigations
Time Frame
Baseline and day 85
Title
Incidence of paradoxical bronchoconstriction
Time Frame
up to day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of bronchial asthma according to the ATS (American Thoracic Society)
Age: 18 - 65 years
Screening FEV1: 40 - 80 % of predicted normal. Predicted normal values will be based on the guidelines for standardised function testing of the European Community for Coal and Steel
Airway obstruction reversibility: increase in FEV1 12% from baseline and ≥ 200 ml from baseline at 30 minutes after 2 puffs of Berodual® MDI
Current non-smoker or ex-smoker (with a smoking history of ≤ 10 pack-years) with cessation of smoking ≥ 1 year prior to the screening visit
Male or female patients
Ability to be trained in proper use of MDI and RESPIMAT® devices
Ability to perform technically satisfactory pulmonary function tests
No hospital admission for an exacerbation and stable dosage of all pulmonary medication in the last four weeks (except for long acting β2 agonists)
Willingness and ability to sign informed consent form prior to participation in the trial
Exclusion Criteria:
Patients with significant disease other than asthma, e.g. history of clinically significant cardiovascular, renal, neurological, hepatic or endocrine dysfunction. A clinically significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or which may influence the results of the study or the ability of the patient to participate in and complete the study
History of myocardial infarction within the last year
Tuberculosis with indication for treatment
History of cancer within the last five years, excluding treated basal cell carcinoma
Patients who have undergone thoracotomy for pulmonary resection of more than one bullae, or with subsequent impaired thoracic muscle performance leading to unsatisfactory lung function testing
Current psychiatric disorders
History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
An upper or lower respiratory tract infection in the four weeks prior to the screening visit (= Visit 1) or during the 2-week run-in period
Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion
Patients with AST/ALT (aspartate amino transferase/alanine amino transferase) (SGOT/SGPT (serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase)) > 200%, bilirubin > 150% (except isolated bilirubin increase due to Gilbert's Syndrome), or creatinine > 125% of the upper limit of the normal range
Intolerance to aerosolised fenoterol- or ipratropium-containing products, and/or hypersensitivity to any of the MDI ingredients
Patients using oral corticosteroid medication at unstable (i.e. less than 4 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg prednisone per day or 20 mg every other day
Beta-blocker medication
Patients who have taken an investigational drug one month or six half-lives (whichever is greater) prior to the screening visit
History of drug abuse and/or alcoholism
Pregnant or nursing women and women of childbearing potential or less than 2 years postmenopausal, who are not using medically approved means of contraception (oral contraceptives, intra-uterine devices or surgical Sterilisation)
Previous participation in this study
Patients who need more than 8 puffs of salbutamol (100 µg per puff) rescue medication on 3 or more consecutive days during the run-in period
Severe bronchial asthma with frequent nocturnal asthma attacks or acute exacerbations induced by recurrent bronchial infections several times per year
Patients with known hypersensitivity to anticholinergic drugs
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
Patients with known narrow-angle glaucoma
Patients who did not fill in at least 80% of the diary in the run-in period for both, medication taken and peak expiratory flow rate (PEFR) measurements are considered not compliant
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/215/215.1104_U01-1083.pdf
Description
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Safety and Efficacy of Berodual® Respimat® Compared to Berodual® MDI (Metered Dose Inhaler) in Asthma Patients
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