Study to Evaluate Safety, Tolerability and Pharmacokinetics of Multiple Rising of BEA 2180 BR in Japanese Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to evaluate safety, tolerability, and pharmacokinetics of BEA 2180 BR in Japanese healthy volunteers

Official Title
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A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Evaluate Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses (50 μg, 100 μg and 200 μg q.d. for 14 Days) of BEA 2180 BR in Japanese Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BEA 2180 BR - rising dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese men: According to the results of a complete medical history, the physical examination, vital signs (blood pressure and pulse rate), 12-lead ECG, clinical laboratory tests Age ≥20 and ≤35 years Body mass index (BMI) ≥18.5 and ≤25 kg/m2 Subjects must be able to inhale medication in a competent manner from the Respimat® Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) 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 drug or its excipients Intake of drugs with a long half-life (>24 hours) within one month or less than 10 half-lives of the respective drug before drug administration or during the trial Use of prescription or non-prescription drugs within 10 days before drug Administration or during the trial. However, over-the-counter (OTC) drugs for external application (such as lubricant eye drops for contact lens, insect bite reliever) shall be allowed Participation in another trial with an investigational drug within four months before drug 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 (≥60 g/day: corresponds to ca. 3 large bottles of beer, 3 gous (ca. 540 cc) of Japanese sake, 6 shots of whisky, 6 glasses of wine or 6 glasses of Japanese shochu, distilled alcoholic beverage) Drug abuse Blood donation (≥100 mL within four weeks before drug administration or during the trial) Excessive physical activities (within one week before drug administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site Exclusion criteria specific for this study: Occupational (professional) exposure to antimuscarinic substances (e.g., physician, nurse, pharmacist etc.; volunteers working for medical institutions, research institutions or herb gardens) History of glaucoma, urination difficulty (due to prostatic hyperplasia etc.)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEA 2180 BR - rising dose<br> | Drug: BEA 2180 BR - rising dose<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with abnormal findings in physical examination |  | up to 28 days after last dose administration | 
| Number of subjects with clinically significant changes in vital signs | Blood pressure and pulse rate | up to 28 days after last dose administration | 
| Number of subjects with clinically significant changes in 12-lead electrocardiogram (ECG) |  | up to 28 days after last dose administration | 
| Number of subjects with abnormal changes in laboratory parameters |  | up to 28 days after last dose administration | 
| Number of subjects with adverse events |  | up to 28 days after last dose administration | 
| Assessment of tolerability by the investigator on a 4-point scale |  | 28 days after last dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 648:00 hours | 
| tmax (time from dosing to maximum measured concentration of the analyte in plasma) |  | up to 648:00 hours | 
| AUCτ (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ) |  | up to 648:00 hours | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz) |  | up to 648:00 hours | 
| Aeτ (amount of analyte that is eliminated in urine over a uniform dosing interval τ) |  | up to 648:00 hours | 
| feτ (fraction of analyte eliminated in urine over a uniform dosing interval τ) |  | up to 648:00 hours | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | up to 648:00 hours | 
| Cmin,ss (minimum concentration of the analyte in plasma at steady state) |  | up to 648:00 hours | 
| Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose) |  | up to 648:00 hours | 
| λz,ss (terminal rate constant in plasma at steady state) |  | up to 648:00 hours | 
| t1/2,ss (terminal half-life of the analyte in plasma at steady state) |  | up to 648:00 hours | 
| MRTih,ss (mean residence time of the analyte in the body at steady state after inhalation administration) |  | up to 648:00 hours | 
| CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration) |  | up to 648:00 hours | 
| Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) |  | up to 648:00 hours | 
| Accumulation ratio of the analyte in plasma based on Cmax (RA,Cmax) |  | up to 648:00 hours | 
| Accumulation ratio of the analyte in plasma based on AUC (RA,AUC) |  | up to 648:00 hours | 
| Accumulation ratio of the analyte in plasma based on Ae (RA,Ae) |  | up to 648:00 hours |