Effects and Safety of Different Dose of Bambuterol on Chinese COPD Patients

Study Overview
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Brief Summary
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This is a randomized, double-blind, 3-crossover trial with a 7-days washout baseline period followed by three treatment periods of 21-days each performed in patients with COPD. Patients will be randomized to receive three treatments (bambuterol 10mg, bambuterol 5 mg and placebo).

Detailed Description
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Patients with COPD who meet the inclusion criteria will enter the 7-days washout baseline period. After the baseline period, patients will be randomly assigned to one of the following treatment sequences: Sequence I: bambuterol 10mg (21 days) -washout (7 days) - bambuterol 5mg (21 days) - washout (7 days) - placebo (21 days); Sequence II: bambuterol 5mg (21 days) -washout (7 days) - placebo (21 days) - washout (7 days) - bambuterol 10mg (21 days) ; Sequence III: placebo (21 days) -washout (7 days) - bambuterol 10mg (21 days) - washout (7 days) - bambuterol 5mg (21 days). During the treatment period patients will record their adverse events and use of rescue medication (Ipratropium bromide) in a diary. At each visit, pulmonary function tests will be performed. At V2, V4 and V6, forced expiratory volume at one second (FEV1) and forced vital capacity (FVC) are measured at following times: immediately before tablet treatment, and at 0.5, 1, 2, 3, 4, 6, 9, 12hrs after administration of tablets, FEV1 and FVC area under curve (AUC) 0 12 hours will be analyzed. At V1, V3, V5 and V7, and FVC are measured a time in the morning. Peak expiratory flow rate (PEFR) is measured by Mini-Wright peak flow meter in the morning before treatments. All other data will be evaluated as safety status, and monitoring of adverse events.

Official Title
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A 12-week, Double-blind, Multicenter, 3-crossover, Placebo Controlled and Randomized Trial to Investigate the Efficacy and Safety of 10mg and 5mg Bambuterol Tablets Once Daily in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD

Intervention / Treatment
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* Drug: bambuterol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD, the disease is under a stable phase Giving written informed consent Age 40 - 80 years (both inclusive) Chinese ethnicity 30% of predicated normal ≤Post bronchodilator FEV1 ≤ 70% of predicated normal Post bronchodilator FEV1/FVC ≤ 70% (Note: post bronchodilator FEV1 will be tested 20-30 minutes after Salbutamol is used (inhaled via metered dose inhaler (MDI) and spacer). Exclusion Criteria: COPD acute exacerbation 4 weeks prior to the enrollment Patients with a history of asthma, allergic rhinitis, atopy Use of disallowed drugs Clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the Investigator) Severe psychiatric or neurological disorders Congestive heart failure severity grade IV according to New York Heart Association (NYHA) Haemodynamically significant cardiac arrhythmias or heart valve deformations CT or X-ray findings indicating an acute pulmonary disease other than COPD (e.g. tuberculosis, severe bronchiectasis, tumors) Severe immunological diseases (e.g. HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy) Severe acute infectious diseases (e.g. tuberculosis or acute hepatitis) Any diagnosis of a malignant disease (except basal cell carcinoma) within 5 years before trial start Alcohol or drug abuse within the past year Suspected hypersensitivity to the Bambuterol or ingredients thereof, or any other contraindication for the use thereof Pregnancy, breast feeding, planned oocyte donation or oocyte implantation Participation in another trial (use of investigational product) within 30 days preceding the baseline visit V1 or re-entry of patients previously enrolled in this trial Suffering from any concomitant disease that might interfere with trial procedures or evaluations

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sequence I<br>10mg (21 days) -washout (7 days) - bambuterol 5mg (21 days) -washout (7 days) -placebo (21 days) | Drug: bambuterol<br>* Patients will be randomized allocated to receive three treatment sequences I, II and III, every treatment period is separated by a washout period of 7 days.<br>* Other names: Bambec, KWD-2183;Drug: Placebo<br> <br> |
| Experimental: sequence II<br>bambuterol 5mg (21 days) -washout (7 days) - placebo (21 days) -washout (7 days) - bambuterol 10mg (21 days) | Drug: bambuterol<br>* Patients will be randomized allocated to receive three treatment sequences I, II and III, every treatment period is separated by a washout period of 7 days.<br>* Other names: Bambec, KWD-2183;Drug: Placebo<br> <br> |
| Experimental: sequence III<br>placebo (21 days) -washout (7 days) - bambuterol 10mg (21 days) - washout (7 days) - bambuterol 5mg (21 days) | Drug: bambuterol<br>* Patients will be randomized allocated to receive three treatment sequences I, II and III, every treatment period is separated by a washout period of 7 days.<br>* Other names: Bambec, KWD-2183;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change in FEV1(L) and FVC(L) | The primary endpoints will be the difference in FEV1 as well as FVC between pre-treatment and post-treatment at respective treatment period (ie. Visit 2(0 week) and Visit 3(3 week), Visit 4 (4 week)and Visit 5(7 week), Visit 6 (8 week) and Visit 7(11 week)) . | pre- and post-treatment during 0 to 3 week, 4 to 7 week and 8 to 11 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference of AUC(0-12h) FEV1(L) as well as AUC(0-12h) FVC(L) among 3 dose groups | AUC FEV1: 0-12h in V2 (0 week), V4 (4 week) and V6 (8 week), AUC FVC: 0-12h in V2 (0 week), V4 (4 week) and V6 (8 week), | at 0, 4, 8 week | 
| change of PEFR(L/min) | difference of Peak flow rate (PEFR) during the treatment period among 3 dose groups | during 0 to 3 week, 4 to 7 week and 8 to 11 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy, safety, Bambuterol tablets, COPD