Clinical trial NCT02173782: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-25
Enrollment: 892
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Average forced expiratory volume in one second (FEV1) between 0 and 1 hour (Area under the curve (AUC0-1h)) in litres
timeFrame: after 12 weeks of treatment
Secondary outcomes:
measure: Average (FEV1) between 0 and 1 hour (AUC0-1h) in litres on previous test days
timeFrame: on day 1, 29, 57
measure: Forced vital capacity (FVC) in litres measured at the same time as FEV1
timeFrame: on day 1, 29, 57 and 85
measure: Peak FEV1 between 0 and 1 hour post inhalation of study drug
timeFrame: on day 1 and 85
measure: Onset of bronchodilatory response
timeFrame: on day 1 and 85
measure: Peak expiratory flow (PEF) measured pre-medication, morning and evening, averaged weekly
timeFrame: up to 12 weeks
measure: Symptom scores recorded on the patient diary card
timeFrame: up to 12 weeks
measure: Use of rescue bronchodilator medication
timeFrame: up to 12 weeks
measure: Number of patients with adverse events
timeFrame: up to 12 weeks
measure: Total average FEV1 (TAUC0-1h)
timeFrame: day 85
measure: Number of patients with clinically significant changes in vital signs
timeFrame: up to 12 weeks
measure: Number of patients with clinically significant changes in laboratory parameters
timeFrame: Baseline and day 85
measure: Number of patients with abnormal findings in physical examination
timeFrame: Baseline and day 85
measure: Number of patients with clinically significant changes in electrocardiogram
timeFrame: Baseline and day 85
Other outcomes:
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