COPD
Conditions
Keywords
efficacy, safety, Bambuterol tablets, COPD
Brief summary
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
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.
Interventions
DRUGbambuterol
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.
DRUGPlacebo
Sponsors
Nanfang Hospital, Southern Medical University
Guangzhou First People's Hospital
The First Affiliated Hospital of Guangzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the change in FEV1(L) and FVC(L) | pre- and post-treatment during 0 to 3 week, 4 to 7 week and 8 to 11 week | 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)) . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| difference of AUC(0-12h) FEV1(L) as well as AUC(0-12h) FVC(L) among 3 dose groups | at 0, 4, 8 week | * 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), |
| change of PEFR(L/min) | during 0 to 3 week, 4 to 7 week and 8 to 11 week | difference of Peak flow rate (PEFR) during the treatment period among 3 dose groups |
Other
| Measure | Time frame | Description |
|---|---|---|
| use of rescue medication | during 0 to 3week,4 to 7 week and 8 to 11 week | •difference of use of rescue medication (Ipratropium bromide) during the treatment period among 3 dose groups |
| electrocardiogram (ECG) | at -1,0,3,4,7,8,11 week | Electrocardiogram (ECG) will be assessed at all visits |
| The Baseline Dyspnea Index (BDI) and Transition Dyspnoea Index (TDI) | BDI at 0, 4 and 8 week, TDI at 3, 7 and 11 week | The Baseline Dyspnea Index (BDI) will be collected before each treatment period, ie. at visits of 2, 4, 6. Transition Dyspnoea Index (TDI) will be collected at the end of each treatment period, ie. at visits of 3, 5, 7. |
| Tremor, Palpitation | up to 11 weeks | Difference of frequency and severity of tremor, palpitation and other adverse events among 3 dose groups will be collected and analyzed during the whole study period. |
Countries
China
Outcome results
None listed