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)

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT02173782

Collaborator

(none)

892

Enrollment

Arms

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Berodual® Respimat ® high dose Drug: Berodual® Respimat ® low dose Drug: Berodual® MDI Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

892 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 1998

Actual Primary Completion Date :

Apr 1, 1999

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Berodual® Respimat ® high dose	Drug: Berodual® Respimat ® high dose
Active Comparator: Berodual® MDI	Drug: Berodual® MDI
Experimental: Berodual® Respimat® low dose	Drug: Berodual® Respimat ® low dose
Placebo Comparator: Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

Average forced expiratory volume in one second (FEV1) between 0 and 1 hour (Area under the curve (AUC0-1h)) in litres [after 12 weeks of treatment]

Secondary Outcome Measures

Average (FEV1) between 0 and 1 hour (AUC0-1h) in litres on previous test days [on day 1, 29, 57]
Forced vital capacity (FVC) in litres measured at the same time as FEV1 [on day 1, 29, 57 and 85]
Peak FEV1 between 0 and 1 hour post inhalation of study drug [on day 1 and 85]
Onset of bronchodilatory response [on day 1 and 85]
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 [up to 12 weeks]
Symptom scores recorded on the patient diary card [up to 12 weeks]
Use of rescue bronchodilator medication [up to 12 weeks]
Number of patients with adverse events [up to 12 weeks]
Total average FEV1 (TAUC0-1h) [day 85]
Number of patients with clinically significant changes in vital signs [up to 12 weeks]
Number of patients with clinically significant changes in laboratory parameters [Baseline and day 85]
Number of patients with abnormal findings in physical examination [Baseline and day 85]
Number of patients with clinically significant changes in electrocardiogram [Baseline and day 85]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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