Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses of BI 11054 CL Administered With the Respimat® in Healthy Male Volunteers

Study Overview
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Brief Summary
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To investigate safety, tolerability, and pharmacokinetics of BI 11054

Official Title
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A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses (0.5 μg to 70 μg Administered With the Respimat®) of BI 11054 CL in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 11054 CL
* Drug: Placebo


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 Body mass index (BMI) ≥18.5 and <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: Any finding of the medical examination (including BP, 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 randomisation 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 (more than 40 g alcohol a day) 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 ß2-mimetics: Asthma or history of pulmonary hyperreactivity Hyperthyrosis Allergic rhinitis in need of treatment Clinically relevant cardiac arrhythmia Paroxysmal tachycardia (>100 beats per minute)

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 11054 CL<br> | Drug: BI 11054 CL<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 clinically significant findings in physical examination |  | up to 18 days after drug administration | 
| Number of subjects with clinically significant findings in vital signs | blood pressure (BP), pulse rate (PR), respiratory rate (RR) | up to 18 days after drug administration | 
| Number of subjects with clinically significant findings in orthostasis tests |  | up to 24 hours after drug administration | 
| Number of subjects with clinically significant findings in laboratory tests |  | up to 18 days after drug administration | 
| Number of subjects with clinically significant findings in additional safety laboratory tests | cyclic adenosine monophosphate (cAMP) and potassium | up to 24 hours after drug administration | 
| Number of subjects with clinically significant changes in body temperature |  | up to 24 hours after drug administration | 
| Number of subjects with clinically significant findings in electrocardiogram (ECG) |  | up to 18 days after drug administration | 
| Number of subjects with adverse events |  | up to 18 days after drug administration | 
| Number of subjects with findings of oropharyngeal inspection |  | up to 24 hours after drug administration | 
| Number of subjects with findings of pulmonary auscultation |  | up to 24 hours after drug administration | 
| Airway resistance (Raw) | measured by body plethysmography | up to 24 hours after drug administration | 
| Global tolerability assessed by investigator on a 4-point scale |  | up to 18 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 96 hours | 
| tmax (time from dosing to maximum measured concentration) |  | up to 96 hours | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable analyte plasma concentration) |  | up to 96 hours | 
| AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval from time t1 to time t2) |  | up to 96 hours | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 96 hours | 
| %AUCtz-∞ (percentage of the AUCtz-∞ that is obtained by extrapolation) |  | up to 96 hours | 
| λz (terminal rate constant in plasma) |  | up to 96 hours | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 96 hours | 
| MRTih (mean residence time of the analyte in the body after inhalation) |  | up to 96 hours | 
| CL/F (apparent clearance of the analyte in plasma after extravascular administration) |  | up to 96 hours | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 96 hours | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | up to 96 hours | 
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) |  | up to 96 hours | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | up to 96 hours |