Clinical trial NCT01796730: Effects and Safety of Different Dose of Bambuterol on Chinese COPD Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COPD
Keywords: efficacy
safety
Bambuterol tablets
COPD
Lead sponsor: The First Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Nanfang Hospital, Southern Medical University
name: Guangzhou First People's Hospital
First posted: 2013-02-22
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: the change in FEV1(L) and FVC(L)
timeFrame: pre- and post-treatment during 0 to 3 week, 4 to 7 week and 8 to 11 week
Secondary outcomes:
measure: difference of AUC(0-12h) FEV1(L) as well as AUC(0-12h) FVC(L) among 3 dose groups
timeFrame: at 0, 4, 8 week
measure: change of PEFR(L/min)
timeFrame: during 0 to 3 week, 4 to 7 week and 8 to 11 week
Other outcomes:
measure: use of rescue medication
timeFrame: during 0 to 3week,4 to 7 week and 8 to 11 week
measure: The Baseline Dyspnea Index (BDI) and Transition Dyspnoea Index (TDI)
timeFrame: BDI at 0, 4 and 8 week, TDI at 3, 7 and 11 week
measure: Tremor, Palpitation
timeFrame: up to 11 weeks
measure: electrocardiogram (ECG)
timeFrame: at -1,0,3,4,7,8,11 week
Locations:
city: Guangzhou
country: China
facility: Guangzhou First Municipal People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Institution of Respiratory Disease (GIRD), The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Guagnzhou Institute of Respiratory Disease, First affiliated hospital of Guangzhou Medical University
name: Jinping Zheng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McDonald CF, Pierce RJ, Thompson PJ, Allen D, Bowler S, Breslin AB, Bowes G, Saunders N, Murree-Allen K, Frith P, Musk AW. Comparison of oral bambuterol and terbutaline in elderly patients with chronic reversible airflow obstruction. J Asthma. 1997;34(1):53-9. doi: 10.3109/02770909709071203.
citation: Cazzola M, Calderaro F, Califano C, Di Pema F, Vinciguerra A, Donner CF, Matera MG. Oral bambuterol compared to inhaled salmeterol in patients with partially reversible chronic obstructive pulmonary disease. Eur J Clin Pharmacol. 1999 Jan;54(11):829-33. doi: 10.1007/s002280050561.