Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses of BEA 2180 BR in Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
Study to investigate safety and tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of BEA 2180 BR

Official Title
-----------------
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (20 µg, 50 µg, 100 µg, 200 µg and 400 µg) of BEA 2180 BR for 21 Days in Healthy Male Volunteers (Double-blind, Randomised, Placebo Controlled [at Each Dose Level] Study)

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BEA 2180 BR
* Drug: Placebo
* Device: Respimat®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males according to the following criteria (examined at the Screening Visit): Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests 1.1 No finding deviating from normal and of clinical relevance 1.2 No evidence of a clinically relevant concomitant disease Age ≥30 and ≤55 years BMI ≥18.5 and BMI < 30 kg/m2 (Body Mass Index) 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 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 Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking 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 if indicative of underlying disease or poor health Exclusion criteria specific for this study: Asthma or chronic obstructive pulmonary disease Glaucoma Urinary tract obstruction Occupational (professional) exposure to antimuscarinic substances

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEA 2180 BR<br> | Drug: BEA 2180 BR<br> <br> Device: Respimat®<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> Device: Respimat®<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with abnormal findings in physical examination |  | up to day 42 | 
| Number of subjects with clinically significant changes in vital signs |  | up to day 42 | 
| Number of subjects with clinically significant changes in 12-lead electrocardiogram |  | up to day 42 | 
| Number of subjects with clinically significant changes in laboratory parameters |  | up to day 42 | 
| Changes in effective airway resistance (Reff) | Body plethysmography | up to day 25 | 
| Changes in specific effective airway conductance (SGeff) | Body plethysmography | up to day 25 | 
| Changes in salivary secretion |  | up to day 21 | 
| Number of subjects with adverse events |  | up to day 42 | 
| Assessment of tolerability by the Investigator on a 4-point rating scale |  | day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of the analyte in plasma for several time points |  | up to day 35 | 
| Time from dosing to maximum concentration in plasma for several time points |  | up to day 35 | 
| Area under the concentration-time curve of the analyte in plasma for several time points |  | up to day 35 | 
| Amount of analyte that is eliminated in urine for several time points |  | up to day 34 | 
| Fraction of analyte excreted in urine for several time points |  | up to day 34 | 
| Renal clearance of the analyte in plasma for several time points |  | up to day 34 | 
| Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval |  | up to day 35 | 
| Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose |  | up to day 35 | 
| Terminal rate constant in plasma at steady state (λz,ss) |  | up to day 35 | 
| Terminal half-life of the analyte in plasma at steady state (t1/2,ss) |  | up to day 35 | 
| Mean residence time of the analyte in the body after 21 administrations at steady state (MRTih,ss) |  | up to day 35 | 
| apparent clearance of the analyte in the plasma after extravascular administration at steady state (CL/F,ss) |  | up to day 35 | 
| apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/F,ss) |  | up to day 35 | 
| Accumulation ratio (RA) of the analyte in plasma after multiple dose administration over a uniform dosing interval τ |  | up to day 35 | 
| Peak trough fluctuation (PTF) |  | up to day 35 |