Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD): a Randomized, 3-week Multiple-dose, Placebo Controlled, Intraformulation Double-blind, Parallel Group Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 202
- 主要终点
- Forced expiratory volume in one second (FEV1) with emphasis on the last two hours of the 24-hour dosing interval (trough FEV1)
研究概览
简要总结
This pharmacodynamic and pharmacokinetic dose-ranging study aims to determine the optimal dose of tiotropium inhaled as a solution from a Respimat device once a day for three weeks in patients with 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
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
- •Age: ≥ 40 years;
- •Diagnosis of COPD and met the following criteria:
- •Relatively stable, moderate to severe airway obstruction,
- •Baseline 30% ≤ FEV1 ≤ 65% of predicted normal value, predicted normal values are based on the guidelines for standardized lung function testing of the European Community for Coal and Steel (ECCS) ,
- •Baseline FEV1/ forced expiratory vital capacity (FEVC) ≤ 70%;
- •Smoking history ≥ 10 pack-years (p.y.). A p.y. is defined as the equivalent of smoking one pack of cigarettes per day for one year;
- •Male of female;
- •Ability to be trained in the proper use of Respimat and Handihaler;
- •Ability to be trained in the performance of technically satisfactory pulmonary function tests;
- •Ability to provide written informed consent
- •Patient affiliated to the Social Security System
排除标准
- •History of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm³
- •Changes in the therapeutic (pulmonary) plan within the last six weeks prior to the Screening Visit;
- •Treatment by cromolyn/nedocromil sodium;
- •Treatment by antihistamines (H1 receptor antagonists);
- •A lower respiratory tract infection or any exacerbation in the past six weeks prior to the Screening Visit;
- •Regular use of daytime oxygen therapy;
- •Treatment by oral corticosteroid medication if initiated or modified within the last six weeks or if daily dose > 10 mg prednisone equivalent;
- •History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis
- •Patients who have undergone thoracotomy with pulmonary resection;
- •History of clinically significant cardiovascular, renal neurologic, liver or endocrine dysfunction. A clinically significant disease was defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
- •Patients with a recent (≤ one year) history of myocardial infarction, of heart failure or patients with any cardiac arrhythmia requiring drug therapy;
- •Tuberculosis with indication for treatment;
- •History of cancer within the last five years. Patients with treated basal cell carcinoma were allowed:
- •Current psychiatric disorders;
- •Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction;
- •Patients with any history of glaucoma or increased intra-ocular pressure;
- •Patients with clinically significant abnormal baseline haematology or blood chemistry, if the abnormality defines a disease listed as an exclusion criterion;
- •Patients with
- •glutamyl-oxalo-acetic transaminase/glutamyl-pyruvic transaminase (SGOT/SGPT): > 200% of the upper limit of the normal range (ULN, )
- •bilirubin: > 150% of the ULN,
- •creatinine: > 125% of the ULN;
- •Intolerance to aerosolised anticholinergic containing products, and/or hypersensitivity to benzalkonium chloride, to lactose or any other components of the inhalation capsule delivery system;
- •Beta-blocker medication;
- •Concomitant or recent (within the last month) use of investigational drugs;
- •History of drug abuse and/or alcoholism;
- •Pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception ( urinary pregnancy test at screening);
- •Previous participation in this study (i.e. having been allocated a randomised treatment number);
- •Patients deprived of their freedom by a judicial or administrative decision;
- •Minors, adults under guardianship;
- •Persons in medical or social establishments;
- •Patients in emergency situations
研究组 & 干预措施
Placebo lactose powder Handihaler
干预措施: Handihaler (Device)
Tiotropium-2.5 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff
干预措施: Tiotropium 1.25 mcg/puff (Drug)
Tiotropium-2.5 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff
干预措施: Respimat (Device)
Tiotropium-1.25 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff
干预措施: Tiotropium 0.625 mcg/puff (Drug)
Tiotropium-1.25 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff
干预措施: Respimat (Device)
Tiotropium-5 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff
干预措施: Tiotropium 2.5 mcg/puff (Drug)
Tiotropium-5 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff
干预措施: Respimat (Device)
Tiotropium-10 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff
干预措施: Tiotropium 5 mcg/puff (Drug)
Tiotropium-10 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff
干预措施: Respimat (Device)
Tiotropium-20 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff
干预措施: Tiotropium 10 mcg/puff (Drug)
Tiotropium-20 Respimat
Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff
干预措施: Respimat (Device)
Placebo Respimat
干预措施: Placebo solution (Drug)
Placebo Respimat
干预措施: Respimat (Device)
Tiotropium-18 lactose powder Handihaler
干预措施: Tiotropium-18 lactose powder (Drug)
Tiotropium-18 lactose powder Handihaler
干预措施: Handihaler (Device)
Placebo lactose powder Handihaler
干预措施: Placebo lactose powder (Drug)
结局指标
主要结局
Forced expiratory volume in one second (FEV1) with emphasis on the last two hours of the 24-hour dosing interval (trough FEV1)
时间窗: last two hours of the 24-hour dosing interval
次要结局
- Forced expiratory volume in one second (FEV1)(during the first four hours post dose)
- Chronic obstructive pulmonary disease symptom scores, physician's global evaluation, sleep question and use of rescue medication(3 weeks treatment period)
- Forced Vital Capacity (FVC)(during first four hours post dose)
- Pharmacokinetic evaluation: 2-hours urine sampling pre- and post-dose (10 patients per group)(before and after last drug administration at day7,14 and 21.)
- Changes in ECG, physical examination, haematology and biochemistry recorded before and after the trial(Screening, 24 to 28 days after treatment)
- Occurrence of adverse events(up to 28 days)
- Changes in ECG, pulse rate (PR) and blood pressure (BP) from the pre-dose values recorded on test day(Day 0, day 7, day 14, day 21)