Randomised, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 3 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination With 5 Microgram Tiotropium Bromide (Delivered by the Respimat Inhaler) Compared With 5 Microgram Tiotropium Bromide Monoproduct (Delivered by the Respimat Inhaler) in Patients With COPD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 360
- 试验地点
- 37
- 主要终点
- Trough FEV1 Response [L] After 4 Weeks of Treatment
研究概览
简要总结
The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 micrograms tiotropium bromide solution for inhalation, delivered by the Respimat inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
- •All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
- •Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 greater or equal 30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1 / FVC <70% at Visit 1
- •Male or female patients, 40 years of age or older
- •Patients must be current or ex-smokers with a smoking history of more than 10 pack years
- •Patients must be able to perform technically acceptable pulmonary function tests and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol
- •Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI).
- •Further inclusion criteria apply
排除标准
- •Patients with a significant disease other than COPD
- •Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
- •Patients with a history of asthma or a total blood eosinophil count >= 600/mm
- •Patients with any of the following conditions:a diagnosis of thyrotoxicosis, a diagnosis of paroxysmal tachycardia (>100 beats per minute), a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTcF* interval > 450 ms), a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
- •Patients with any of the following conditions:a history of myocardial infarction within 1 year of screening visit (Visit 1), a diagnosis of clinically relevant cardiac arrhythmia, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse
- •Patients who have undergone thoracotomy with pulmonary resection
- •Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
- •Pregnant or nursing women
- •Women of childbearing potential not using two effective method of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years
- •Patients who have previously been randomized in this study or are currently participating in another study
- •Patients who are unable to comply with pulmonary medication restrictions prior to randomization
- •Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit
- •Further exclusion criteria apply
研究组 & 干预措施
BI 1744 CL low dose/tiotropium bromide
BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: BI 1744 CL/tiotropium bromide fixed dose combination (Drug)
BI 1744 CL low dose/tiotropium bromide
BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: Respimat® Inhaler (Device)
BI1744CL medium dose/tiotropium bromide
BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: BI 1744 CL/tiotropium bromide fixed dose combination (Drug)
BI1744CL medium dose/tiotropium bromide
BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: Respimat® Inhaler (Device)
BI 1744 CL high dose/tiotropium bromide
BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: BI 1744 CL/tiotropium bromide fixed dose combination (Drug)
BI 1744 CL high dose/tiotropium bromide
BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: Respimat® Inhaler (Device)
tiotropium bromide
tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: tiotropium bromide (Drug)
tiotropium bromide
tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
干预措施: Respimat® Inhaler (Device)
结局指标
主要结局
Trough FEV1 Response [L] After 4 Weeks of Treatment
时间窗: Baseline and 4 weeks
Trough FEV1 (Forced expiratory volume in 1 second) was defined as the mean of the two FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
次要结局
- Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.(Baseline, 1 week and 2 weeks)
- Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment(Baseline, 1 week, 2 weeks and 4 weeks)
- FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment(1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks)
- FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.(1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks)
- PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.(1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks)
- FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment(1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29))
- FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment(5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks)
- FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment(5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks)
- PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment(5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks)
- FEV1 and PEF (Unsupervised) AUC(0-6h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment(After first administration, 1 week, 2 weeks and 4 weeks)
- FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment(6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks)
- Tmax,ss Olodaterol [h](Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.)
- FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment(1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29))
- PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment(1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29))
- PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment(6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks)
- Weekly Mean Pre-dose Morning PEF [L/Min](Throughout the 4 week treatment period)
- Weekly Mean Evening PEF [L/Min](Throughout the 4 weeks treatment period)
- Weekly Mean Number of Occasions of Rescue Therapy Used Per Day(Throughout the 4 weeks treatment period)
- Physician's Global Evaluation(1 week, 2 weeks and 4 weeks)
- Patient's Global Rating(4 weeks)
- Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities(From first dose up to 21 days after last dose of study medication.)
- Cmax,ss Olodaterol [pg/mL](Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.)
- AUC(0-1h,ss) Olodaterol [pg*h/mL](Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.)
- Cmax,ss Tiotropium [pg/mL](Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.)
- Tmax,ss Tiotropium [h](Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.)
- AUC(0-3h,ss) Tiotropium [pg*h/mL](Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.)