To Assess Safety, Tolerability and Pharmacokinetics of BI 443651 in Healthy Male Volunteers

Study Overview
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Brief Summary
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To investigate safety, tolerability and pharmacokinetics, following single doses of BI 443651

Official Title
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Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses of BI 443651 in Healthy Male Volunteers in a Partially Randomised, Single Blind, Placebo-controlled Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 443651
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests Age of 18 to 50 years (incl.) BMI of 18.5 to 29.9 kg/m2 (incl.) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair) Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders History of relevant orthostatic hypotension, fainting spells, or blackouts Chronic or relevant acute infections History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) Inability to refrain from smoking on specified trial days Alcohol abuse (consumption of more 30 g per day for males) Drug abuse or positive drug screening Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial Inability to comply with dietary regimen of trial site A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant ECG finding at screening A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study The subject has a diagnosis history of pulmonary hyperreactivity. Estimated glomerular filtration rate (eGFR) below 80 mL/min

Ages Eligible for Study
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Minimum Age: 18 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: BI 443651<br> | Drug: BI 443651<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 |
| --- | --- | --- |
| Percentage of Subjects With Drug-related Adverse Events (AEs) | This outcome measure presents percentage of the subjects with drug-related AEs. The doses ranged from 10 μg to 3600 μg for the outcome measure [Percentage of subjects with drug-related Adverse Events (AEs)]. | Up to 216 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) | This outcome measure presents 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 (AUC0-tz). Time frame note: The time points 72:00h, 96:00h below was only applicable for highest dose (and corresponding placebo subjects). Two blood sample for stability testing were taken at 3:00h time point from the Treatment C dose group only. The doses ranged from 10 μg to 3600 μg for the outcome measure [AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)]. | 1.30 (hours: minutes) hours (h) before drug administration and 0:05h, 0:10h, 0:15h, 0:20h, 0:30h, 0:40h, 0:50h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h, 96:00h after drug administration. | 
| Cmax (Maximum Measured Concentration of the Analyte in Plasma) | This outcome measure presents maximum concentration of analyte in plasma (Cmax). Time frame note: The time points 72:00h, 96:00h below was only applicable for highest dose (and corresponding placebo subjects). Two blood sample for stability testing were taken at 3:00h time point from the Treatment C dose group only. The doses ranged from 10 μg to 3600 μg for the outcome measure [Cmax (maximum measured concentration of the analyte in plasma)]. | 1.30 (hours: minutes) hours (h) before drug administration and 0:05h, 0:10h, 0:15h, 0:20h, 0:30h, 0:40h, 0:50h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h, 96:00h after drug administration. |