Safety, Tolerability and Pharmacokinetics of BEA 2180 BR in Healthy Male Volunteers

Study Overview
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Brief Summary
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Evaluation of safety, tolerability and pharmacokinetics of single rising intravenous doses of BEA 2180 BR; additional exploration of metabolism following inhalation

Official Title
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A Randomised, Single-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Intravenous Doses (2.5 μg, 7.5 μg, 25 μg, 50 μg, 100 μg, 200 μg, 350 μg, 500 μg Free Cation) BEA 2180 BR in Healthy Male Volunteers With an Additional Arm by Inhalation in One Dose Group (1600 μg)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BEA 2180 BR solution for infusion
* Drug: Placebo
* Drug: BEA 2180 BR solution for inhalation
* Device: Respimat®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (BP, PR), 12 lead ECG measurement, and clinical laboratory tests. There is no finding deviating from normal and of clinical relevance. There is no evidence of a clinically relevant concomitant disease. Age ≥21 and ≤50 years BMI ≥18.5 and <29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation. Exclusion Criteria: Any finding of the medical examination (including blood pressure (BP), pulse rate (PR), and ECG measurements) deviating from normal and of clinical relevance Evidence of a clinically relevant concomitant disease 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 relevant allergy/hypersensitivity (including allergy to the drug or its excipients) as judged clinically relevant by the investigator Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives of the respective drug prior to randomisation 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 enrolment in the study or during the study Participation in another trial with an investigational drug within 2 months prior to randomisation Smoker (>10 cigarettes or >3 cigars or >3 pipes/day) Inability to refrain from smoking on trial days as judged by the investigator Alcohol abuse (regularly more than 40 g alcohol per day for men) Drug abuse Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during the trial) Excessive physical activities within 1 week prior to randomisation or during the trial Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of the study centre The following exclusion criteria are specific for this study due to the known class side effect profile of anticholinergic drugs: hypersensitivity to tiotropium and/or related drugs of these classes history of narrow-angle glaucoma history of prostatic hyperplasia history of bladder-neck obstruction

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEA 2180 BR IV<br>Rising doses | Drug: BEA 2180 BR solution for infusion<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Intravenous infusion<br>|
| Experimental: BEA 2180 BR inhalation<br> | Drug: BEA 2180 BR solution for inhalation<br> <br> Device: Respimat®<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with abnormal findings in physical examination |  | Up to day 12 after drug administration | 
| Number of participants with clinically significant changes in vital signs |  | Up to day 12 after drug administration | 
| Number of participants with abnormal findings in 12 - lead ECG (electrocardiogram) |  | Up to day 12 after drug administration | 
| Number of participants with abnormal changes in clinical laboratory parameters |  | Up to day 12 after drug administration | 
| Number of participants with adverse events |  | Up to day 12 after drug administration | 
| Investigator assessed tolerability on a 4-point scale |  | Up to day 12 after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | Up to 72 hours after drug administration | 
| tmax (time from dosing to maximum measured concentration) |  | Up to 72 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | Up to 72 hours after drug administration | 
| %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | Up to 72 hours after drug administration | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | Up to 72 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | Up to 72 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | Up to 72 hours after drug administration | 
| MRT(mean residence time of the analyte in the body) |  | Up to 72 hours after drug administration | 
| CL (total clearance of the analyte in plasma) |  | Up to 72 hours after drug administration | 
| Vz (apparent volume of distribution during the terminal phase λz) |  | Up to 72 hours after drug administration | 
| Vss (apparent volume of distribution at steady state following intravascular administration) |  | Up to 72 hours after drug administration | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | Up to 72 hours after drug administration | 
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) |  | Up to 72 hours after drug administration | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | Up to 72 hours after drug administration |