Safety, Tolerability and Pharmacokinetics Study of BI 1744 CL in Healthy Male Subjects

Study Overview
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Brief Summary
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To investigate safety, tolerability, and pharmacokinetics (PK) of single i.v. doses of BI 1744 CL

Official Title
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Safety, Tolerability and Pharmacokinetics of Single Rising Doses of 0.5 μg, 2.5 μg, 5 μg, 10 μg, 15 μg, 20 μg, 25 μg and 30 μg BI 1744 CL (Calculated as Free Base) Given as Intravenous Infusion Over 30 Minutes to Healthy Male Subjects. A Single-centre, Single-blind, Placebo-controlled, Randomised Study.

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 1744 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 (blood pressure (BP), pulse rate (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 ≤45 years BMI ≥18.5 and <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: 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 medication 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 medication Participation in another trial with an investigational drug within 2 months prior to medication 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 medication 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: 45 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: BI 1744 CL<br>Single rising dose of BI 1744 CL as intravenous (i.v.) infusion | Drug: BI 1744 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 patients with abnormal findings in physical examination |  | Baseline, Day 10 after drug administration | 
| Number of patients with clinically significant changes in vital signs |  | Baseline and up to day 10 after drug administration | 
| Number of patients with abnormal changes in 12-lead ECG (electrocardiogram) parameters |  | Baseline and up to day 10 after drug administration | 
| Number of patients with abnormal changes in laboratory parameters |  | Baseline and up to day 10 after administration | 
| Number of patients with adverse events |  | Up to day 10 | 
| Assessment of tolerability by investigator on a 4-point scale |  | Day 10 after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the concentration-time curve of the analyte in plasma at different time points) |  | Up to 48 hours after drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | Up to 48 hours after drug administration | 
| tmax (time from dosing to maximum measured concentration) |  | Up to 48 hours after drug administration | 
| %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | Up to 48 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | Up to 48 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | Up to 48 hours after drug administration | 
| MRT (mean residence time of the analyte in the body after intravenous administration) |  | Up to 48 hours after drug administration | 
| CL (total clearance of the analyte in plasma after intravascular administration) |  | Up to 48 hours after drug administration | 
| V (apparent volume of distribution at different time points following an intravascular dose) |  | Up to 48 hours after drug administration | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | Up to 96 hours after drug administration | 
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) |  | Up to 96 hours after drug administration | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | Up to 96 hours after drug administration |