Comparison of Safety and Efficacy of Berodual® Administered Via the Respimat® Device With That Administered Via the Metered Dose Inhaler (MDI) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Berodual® Respimat ® high dose
Berodual® Respimat ® low dose
Berodual® MDI
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion Criteria:
- Age >= 40 years
Diagnosis of COPD according the following criteria:
- screening FEV1<= 65% predicted
- Screening FEV1/FVC <= 70%
- Smoking history > 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent
- Able to be trained in the proper use of MDI and Respimat®
- Able to be trained in the performance of technically satisfactory pulmonary function tests
- All patients must be willing and able to sign informed consent in accordance with Good clinical Practice (GCP) and local legislation
Exclusion Criteria:
- History of cardiovascular, renal, neurologic, liver or endocrine dysfunction (e.g. hyperthyreosis) 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 or the study or the patient's ability to participate in the study
- Patients with a recent (<= one year) history of myocardial infarction
- Tuberculosis with indication for treatment
- History of cancer within the last five years (excluding basal carcinoma)
- Patients who have undergone thoracotomy
- Current psychiatric disorders
- History of life-threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
- An upper and lower respiratory tract infection in the four weeks prior to the screening visit
- Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
- Patients with known narrow-angle glaucoma or raised intra-ocular pressure
- Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion
Patients with:
- Serum glutamic oxalo-acetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) >200% of the upper limit of the normal range
- Bilirubin >150% of the upper limit of the normal range
- Creatinine >125% of the upper limit of the normal range
- Patients who are on chronic oxygen therapy
- Intolerance to aerosolised ipratropium- or fenoterol-containing products, or hypersensitivity to any of the MDI ingredients
- Oral corticosteroid mediation at dose greater than 10 mg prednisolone per day or equivalent
- Beta-blocker medication
- Changes in the pulmonary therapeutic plan within the last four weeks prior to the screening visit (not including withholding of medication before the screening visit)
- Concomitant or recent (within the last month) use of investigational drugs
- History of drug abuse and/or alcoholism
- Pregnant or nursing women and women of child-bearing potential not using a medically approved means of contraception
- Previous participation in this study (i.e. having been allocated a randomized treatment number)
- Patients with a history of asthma, allergic rhinitis or atopy or who have blood eosinophil count above 600/mm3 (a repeat eosinophil count will not be conducted in these patients) and those patients on antihistamines, anti-leukotrienes, sodium cromoglycate or nedocromil sodium
- Patients who are unable to comply with the medication restrictions specified in section 4.2 or who cannot use an MDI without a spacer
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Experimental
Placebo Comparator
Arm Label
Berodual® Respimat ® high dose
Berodual® MDI
Berodual® Respimat® low dose
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Average forced expiratory volume in one second (FEV1) between 0 and 1 hour (Area under the curve (AUC0-1h)) in litres
Secondary Outcome Measures
Average (FEV1) between 0 and 1 hour (AUC0-1h) in litres on previous test days
Forced vital capacity (FVC) in litres measured at the same time as FEV1
Peak FEV1 between 0 and 1 hour post inhalation of study drug
Onset of bronchodilatory response
Linear interpolation of the time of the first therapeutic response and the observation just prior to to the first therapeutic response. Therapeutic response was defined as FEV1 measurement exceeding 1.15 times of the pre-dose value that was recorded at any time point during the one hour observation period.
Peak expiratory flow (PEF) measured pre-medication, morning and evening, averaged weekly
Symptom scores recorded on the patient diary card
Use of rescue bronchodilator medication
Number of patients with adverse events
Total average FEV1 (TAUC0-1h)
Number of patients with clinically significant changes in vital signs
Number of patients with clinically significant changes in laboratory parameters
Number of patients with abnormal findings in physical examination
Number of patients with clinically significant changes in electrocardiogram
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02173782
Brief Title
Comparison of Safety and Efficacy of Berodual® Administered Via the Respimat® Device With That Administered Via the Metered Dose Inhaler (MDI) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official Title
A Randomized, Placebo-controlled, Within-device, Double-blind Tri-national Study to Compare the Safety and Efficacy of Berodual® Administered Via the 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 COPD Patients Over a 12-week Period
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
February 1998 (undefined)
Primary Completion Date
April 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
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 the 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 the MDI and that the safety profile is at least as good when COPD patients are treated for 12 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
892 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Berodual® Respimat ® high dose
Arm Type
Experimental
Arm Title
Berodual® MDI
Arm Type
Active Comparator
Arm Title
Berodual® Respimat® low dose
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Berodual® Respimat ® high dose
Intervention Type
Drug
Intervention Name(s)
Berodual® Respimat ® low dose
Intervention Type
Drug
Intervention Name(s)
Berodual® MDI
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Average forced expiratory volume in one second (FEV1) between 0 and 1 hour (Area under the curve (AUC0-1h)) in litres
Time Frame
after 12 weeks of treatment
Secondary Outcome Measure Information:
Title
Average (FEV1) between 0 and 1 hour (AUC0-1h) in litres on previous test days
Time Frame
on day 1, 29, 57
Title
Forced vital capacity (FVC) in litres measured at the same time as FEV1
Time Frame
on day 1, 29, 57 and 85
Title
Peak FEV1 between 0 and 1 hour post inhalation of study drug
Time Frame
on day 1 and 85
Title
Onset of bronchodilatory response
Description
Linear interpolation of the time of the first therapeutic response and the observation just prior to to the first therapeutic response. Therapeutic response was defined as FEV1 measurement exceeding 1.15 times of the pre-dose value that was recorded at any time point during the one hour observation period.
Time Frame
on day 1 and 85
Title
Peak expiratory flow (PEF) measured pre-medication, morning and evening, averaged weekly
Time Frame
up to 12 weeks
Title
Symptom scores recorded on the patient diary card
Time Frame
up to 12 weeks
Title
Use of rescue bronchodilator medication
Time Frame
up to 12 weeks
Title
Number of patients with adverse events
Time Frame
up to 12 weeks
Title
Total average FEV1 (TAUC0-1h)
Time Frame
day 85
Title
Number of patients with clinically significant changes in vital signs
Time Frame
up to 12 weeks
Title
Number of patients with clinically significant changes in laboratory parameters
Time Frame
Baseline and day 85
Title
Number of patients with abnormal findings in physical examination
Time Frame
Baseline and day 85
Title
Number of patients with clinically significant changes in electrocardiogram
Time Frame
Baseline and day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >= 40 years
Diagnosis of COPD according the following criteria:
screening FEV1<= 65% predicted
Screening FEV1/FVC <= 70%
Smoking history > 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent
Able to be trained in the proper use of MDI and Respimat®
Able to be trained in the performance of technically satisfactory pulmonary function tests
All patients must be willing and able to sign informed consent in accordance with Good clinical Practice (GCP) and local legislation
Exclusion Criteria:
History of cardiovascular, renal, neurologic, liver or endocrine dysfunction (e.g. hyperthyreosis) 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 or the study or the patient's ability to participate in the study
Patients with a recent (<= one year) history of myocardial infarction
Tuberculosis with indication for treatment
History of cancer within the last five years (excluding basal carcinoma)
Patients who have undergone thoracotomy
Current psychiatric disorders
History of life-threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
An upper and lower respiratory tract infection in the four weeks prior to the screening visit
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction
Patients with known narrow-angle glaucoma or raised intra-ocular pressure
Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion
Patients with:
Serum glutamic oxalo-acetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) >200% of the upper limit of the normal range
Bilirubin >150% of the upper limit of the normal range
Creatinine >125% of the upper limit of the normal range
Patients who are on chronic oxygen therapy
Intolerance to aerosolised ipratropium- or fenoterol-containing products, or hypersensitivity to any of the MDI ingredients
Oral corticosteroid mediation at dose greater than 10 mg prednisolone per day or equivalent
Beta-blocker medication
Changes in the pulmonary therapeutic plan within the last four weeks prior to the screening visit (not including withholding of medication before the screening visit)
Concomitant or recent (within the last month) use of investigational drugs
History of drug abuse and/or alcoholism
Pregnant or nursing women and women of child-bearing potential not using a medically approved means of contraception
Previous participation in this study (i.e. having been allocated a randomized treatment number)
Patients with a history of asthma, allergic rhinitis or atopy or who have blood eosinophil count above 600/mm3 (a repeat eosinophil count will not be conducted in these patients) and those patients on antihistamines, anti-leukotrienes, sodium cromoglycate or nedocromil sodium
Patients who are unable to comply with the medication restrictions specified in section 4.2 or who cannot use an MDI without a spacer
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/215/215.1349_U00-1190.pdf
Description
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Comparison of Safety and Efficacy of Berodual® Administered Via the Respimat® Device With That Administered Via the Metered Dose Inhaler (MDI) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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