Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Rising Inhaled BEA 2180 BR Doses (2.5 μg to 1600 μg Cation Administered With the Respimat®) in Healthy Male Subjects, Alone and Followed by Methacholine Challenge. A Randomised, Double-blind Within Dose Group, Placebo-controlled Study, With a 36 μg Tiotropium Bromide Single Dose Sub-study (Open, Two-fold Crossover).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 101
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
Main study: To investigate safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of BEA 2180 BR Sub-study; To investigate whether treatment with 36 μg tiotropium bromide is able to protect of methacholine-induced bronchoconstriction compared to baseline (methacholine challenge at screening).
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
- 30 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male volunteers based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory test
- •No finding deviating from normal and of clinical relevance
- •No evidence of a clinically relevant concomitant disease
- •Age ≥ 30 and Age ≤ 55 years
- •Body Mass Index (BMI) ≥ 18.5 and BMI < 30 kg/m2
- •Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation
排除标准
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- •History of relevant orthostatic hypotension, fainting spells or blackouts
- •Chronic or relevant acute infections
- •History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator (or his deputy)
- •Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
- •Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- •Participation in another trial with an investigational drug within two months prior to administration or during the trial
- •Alcohol abuse (more than 60 g/day)
- •Drug abuse
- •Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
- •Excessive physical activities (within one week prior to administration or during the trial)
- •Any laboratory value outside the reference range of clinical relevance
- •Exclusion criteria specific for this study:
- •Bronchial hyperreactivity as demonstrated by a 45% change of SGaw at or below a cumulative methacholine concentration of 10 mg/mL = 1%
- •Asthma or bronchial hyperreactivity
- •Allergic rhinitis (hay fever)
- •Urinary tract obstruction
- •History of cardiovascular disease
- •History of peptic ulcer disease
- •History of thyroid disease
研究组 & 干预措施
BEA 2180 BR
single rising doses
干预措施: BEA 2180 BR (Drug)
BEA 2180 BR
single rising doses
干预措施: Respimat® A 4 (Device)
BEA 2180 BR
single rising doses
干预措施: Methacholine Chloride (Drug)
Placebo
干预措施: Placebo (Drug)
Placebo
干预措施: Respimat® A 4 (Device)
Placebo
干预措施: Methacholine Chloride (Drug)
Sub-Study
干预措施: Methacholine Chloride (Drug)
Sub-Study
干预措施: Spiriva (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: up to 14 days after last drug administration
Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram)
时间窗: up to 14 days after last drug administration
Assessment of tolerability by investigator on a 5-point scale
时间窗: within 14 days after last drug administration
Number of subjects with clinically significant changes in vital signs
时间窗: up to 14 days after last drug administration
blood pressure, pulse rate, respiratory rate, oral body temperature
Number of subjects with clinically significant changes in laboratory parameters
时间窗: up to 14 days after last drug administration
Changes from baseline in airway resistance (Raw)
时间窗: up to 120 hours after drug administration
assessed by body plethysmography
Changes from baseline in specific airway conductance (sGaw)
时间窗: up to 120 hours after drug administration
assessed by body plethysmography
次要结局
- Fraction of administered drug excreted unchanged in urine (fe)(up to 312 hours after drug administration)
- Changes from baseline in salivary secretion(up to 24 hours after drug administration)
- Changes from baseline in pupil diameter of each eye(up to 4 hours after drug administration)
- Maximum measured concentration of the analyte in plasma (Cmax)(up to 240 hours after drug administration)
- Measured concentration of the analyte in plasma (C) for several time points(up to 24 hours after drug administration)
- Amount of parent drug that is eliminated in urine (Ae)(up to 312 hours after drug administration)
- Terminal half-life of the analyte in plasma (t1/2)(up to 240 hours after drug administration)
- Renal clearance of the analyte (CLR)(up to 312 hours after drug administration)
- Area under the concentration-time curve of the analyte in plasma (AUC)(up to 240 hours after drug administration)
- Terminal rate constant of the analyte in plasma (λZ)(up to 240 hours after drug administration)
- Time from dosing to the maximum concentration of the analyte in plasma (tmax)(up to 240 hours after drug administration)
- Mean residence time of the analyte in the body after inhaled administration (MRTinh)(up to 240 hours after drug administration)
- Apparent clearance of the analyte in plasma following extravascular administration (CL/F)(up to 240 hours after drug administration)
- Apparent volume of distribution during the terminal phase λz following an extravascular dose (VZ/F)(up to 240 hours after drug administration)