Efficacy and Safety of Ba679BR Powder Inhalation in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Study to investigate the efficacy and safety of Ba679BR powder inhalation during the continuous once/day administration to the patients with COPD using oxitropium bromide (Tersigan® aerosol) as the comparator drug.

Official Title
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A Multiple Dose Comparison of 18 µg, 36 µg of Ba679BR (Tiotropium) Inhalation Capsules and Oxitropium Metered Dose Inhaler (2 Puffs of 100µg) in a 4-week, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium low
* Drug: Tiotropium high
* Drug: Placebo MDI
* Drug: Placebo inhalation capsule
* Drug: Oxitropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD (chronic bronchitis, and emphysema) with stable symptoms: Screening FEV1.0 ≤70% of predicted normal vale and screening FEV1.0/FVC ≤70% (the baseline FEV1.0 should also be ≤70% of predicted normal value on the initial day of administration) Smoking history ≥ 10 pack-years (a peak-year is 20 cigarettes per day for one year or equivalent) Male or female patients 40 years of age or older Exclusion Criteria: History of bronchial asthma History of an atopic disease such as allergic rhinitis Total blood eosinophil count ≥ 600/µL Patient treated with antiallergic drugs or anti-histamine drugs Patients using oral corticosteroid medication at unstable doses (i.e. less than one month on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisolone per day Patients using inhaled steroid, oral β2 stimulant, theophylline preparation, expectorant or macrolide antibiotic at unstable doses (i.e. less than one month on a stable dose) Patients using an ACE inhibitor at unstable doses (i.e. less than one month on a stable dose) Patients with known narrow-angle glaucoma Patients with known symptomatic prostatic hypertrophy Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system Patients with significant diseases who in the opinion of the investigator were not eligible for the study Patients with clinically significant abnormal baseline laboratory test values (hematology, blood chemistry, urinalysis). Patients with serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) twice the upper limit of the normal range, bilirubin 150% or creatinine 125% of the upper limit of the normal range were excluded Patients with a recent history (i.e. within the 3 months prior to the screening visit) of myocardial infarction or heart failure Patients with any cardiac arrhythmia requiring drug therapy Patients who were treated with Patients who were treated with β-blockers-blockers Patients with regular use of daytime oxygen therapy Patients with known active tuberculosis or with obvious sequela of tuberculosis Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma were allowed Patients with a history of cystic fibrosis or bronchiectasis Patients with upper respiratory tract infection in the past one month prior to the screening visit or during the baseline period Patients who had taken an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit Pregnant or nursing women or women of childbearing potential Other than the above, patients who in the opinion of the investigator were not eligible for the study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium low & Placebo<br>Tiotropium 18 µg inhalation capsule and Placebo MDI | Drug: Tiotropium low<br>* Tiotropium 18 µg inhalation capsule<br>Drug: Placebo MDI<br>* Placebo metered dose inhaler (MDI)<br>|
| Experimental: Tiotropium high & Placebo<br>Tiotropium 36 µg inhalation capsule and Placebo MDI | Drug: Tiotropium high<br>* Tiotropium 36 µg inhalation capsule<br>Drug: Placebo MDI<br>* Placebo metered dose inhaler (MDI)<br>|
| Active Comparator: Oxitropium & Placebo<br>Oxitropium MDI (100 µg/puff) and Placebo inhalation capsules | Drug: Placebo inhalation capsule<br> <br> Drug: Oxitropium<br>* Oxitropium MDI (100 µg/puff)<br>* Other names: Tersigan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough forced expiratory volume in one second (FEV1.0) response |  | Day 1, week 2 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1.0 response at 1 hour after administration |  | Day 1, week 2 and 4 | 
| Trough forced vital capacity (FVC) response |  | Day 1, week 2 and 4 | 
| FVC response at 1 hour after administration |  | Day 1, week 2 and 4 | 
| Peak expiratory flow rate (PEF) |  | in the morning and at evening every day until week 4 | 
| COPD symptom scores |  | until week 4 | 
| Frequency of rescue use of β2 stimulant |  | until week 4 | 
| Patient's impression |  | week 4 | 
| Physician's global evaluation |  | week 4 | 
| Occurrence of Adverse Events |  | up to 4 weeks | 
| Change from baseline in blood pressure |  | Baseline, week 4 | 
| Change from baseline in heart rate |  | Baseline, week 4 | 
| Changes in ECG findings |  | Baseline, week 4 | 
| Changes from baseline in laboratory values |  | Baseline, week 4 |