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).
Overview
- Phase
- Phase 1
- Intervention
- BEA 2180 BR
- Conditions
- Healthy
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 101
- Primary Endpoint
- Number of subjects with adverse events
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
BEA 2180 BR
single rising doses
Intervention: BEA 2180 BR
BEA 2180 BR
single rising doses
Intervention: Respimat® A 4
BEA 2180 BR
single rising doses
Intervention: Methacholine Chloride
Placebo
Intervention: Placebo
Placebo
Intervention: Respimat® A 4
Placebo
Intervention: Methacholine Chloride
Sub-Study
Intervention: Methacholine Chloride
Sub-Study
Intervention: Spiriva
Outcomes
Primary Outcomes
Number of subjects with adverse events
Time Frame: up to 14 days after last drug administration
Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram)
Time Frame: up to 14 days after last drug administration
Assessment of tolerability by investigator on a 5-point scale
Time Frame: within 14 days after last drug administration
Number of subjects with clinically significant changes in vital signs
Time Frame: 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
Time Frame: up to 14 days after last drug administration
Changes from baseline in airway resistance (Raw)
Time Frame: up to 120 hours after drug administration
assessed by body plethysmography
Changes from baseline in specific airway conductance (sGaw)
Time Frame: up to 120 hours after drug administration
assessed by body plethysmography
Secondary Outcomes
- 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)