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

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)

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).

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Placebo; Drug: bambuterol

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Guangzhou First Municipal People's Hospital
    • Guangzhou, Guangdong, China, 510120
      • Guangzhou Institution of Respiratory Disease (GIRD), The First Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: sequence I; 10mg (21 days) -washout (7 days) - bambuterol 5mg (21 days) -washout (7 days) -placebo (21 days)	Drug: Placebo; Drug: bambuterol; 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.; Other Names: Bambec, KWD-2183
EXPERIMENTAL: sequence II; bambuterol 5mg (21 days) -washout (7 days) - placebo (21 days) -washout (7 days) - bambuterol 10mg (21 days)	Drug: Placebo; Drug: bambuterol; 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.; Other Names: Bambec, KWD-2183
EXPERIMENTAL: sequence III; placebo (21 days) -washout (7 days) - bambuterol 10mg (21 days) - washout (7 days) - bambuterol 5mg (21 days)	Drug: Placebo; Drug: bambuterol; 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.; Other Names: Bambec, KWD-2183

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
use of rescue medication	•difference of use of rescue medication (Ipratropium bromide) during the treatment period among 3 dose groups	during 0 to 3week,4 to 7 week and 8 to 11 week
The Baseline Dyspnea Index (BDI) and Transition Dyspnoea Index (TDI)	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.	BDI at 0, 4 and 8 week, TDI at 3, 7 and 11 week
Tremor, Palpitation	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.	up to 11 weeks
electrocardiogram (ECG)	Electrocardiogram (ECG) will be assessed at all visits	at -1,0,3,4,7,8,11 week

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangzhou Medical University
• Collaborators: Guangzhou First People's Hospital; Nanfang Hospital of Southern Medical University
• Investigators: Principal Investigator: Jinping Zheng, MD, Guagnzhou Institute of Respiratory Disease, First affiliated hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: February 5, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (ESTIMATE): February 22, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): March 17, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: safety; COPD; efficacy; Bambuterol tablets
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bambuterol
• Other Study ID Numbers: GIRDBAM201201