Safety, Tolerability and Pharmacokinetics of BI 113608 in Healthy Asian and Caucasian Male Volunteers

Study Overview
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Brief Summary
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Safety, tolerability and pharmacokinetics of single and multiple oral doses of BI 113608 in healthy Chinese, Japanese and Caucasian male volunteers.

Official Title
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Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses and Multiple Rising Oral Doses of BI 113608 in Healthy Male Asian and Caucasian Volunteers (Randomised, Double-blind, Placebo-controlled Within Dose Groups)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 113608
* Drug: Placebo
* Drug: BI 113608
* Drug: Placebo
* Drug: BI 113608
* Drug: BI 113608
* Drug: BI 113608
* Drug: BI 113608


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: -Healthy male volunteers according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead Electrocardiogram, clinical laboratory tests Chinese ethnicity, Japanese ethnicity according to the following criteria Japanese; born in Japan, be a current Japanese passport holder, have lived outside of Japan <10 years, and have parents and grandparents who were all born in Japan Chinese; ethnic Chinese, born in China or ethnic Chinese born outside of China, and a descendent of 4 ethnic Chinese grandparents who were all born in China Caucasian Age older than 20 and younger than 45 years Normal lung function testing Normal peripheral oxygen saturation as determined by non-invasive pulse oxymetry Body Mass Index more than 18.5 and Body Mass Index less than 25 kg/m2 for Japanese and Chinese Body Mass Index more than 18.5 and Body Mass Index less than 29.9 kg/m2 for Caucasians 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 Blood Pressure, Pulse Rate and Electrocardiogram) 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 (including but not limited to any kind of seizures, migraine, stroke or psychiatric disorders) within the past 6 month 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 at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 20 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to 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 A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms); A history of additional risk factors for Torsades de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (Multiple dose)<br>Placebo | Drug: Placebo<br>* Placebo (Multiple dosing)<br>|
| Experimental: Dose 1, Single dose<br>Low dose | Drug: BI 113608<br>* Low dose (Single dosing)<br>|
| Experimental: Dose 2, Single dose<br>Medium dose | Drug: BI 113608<br>* Medium dose (Single dosing)<br>|
| Experimental: Dose 3, Single dose<br>High dose | Drug: BI 113608<br>* High dose (Single dosing)<br>|
| Experimental: Dose 4, Multiple dose<br>Low dose | Drug: BI 113608<br>* Low dose (Multiple dosing)<br>|
| Experimental: Dose 5, Multiple dose<br>Medium dose | Drug: BI 113608<br>* Medium dose (Multiple dosing)<br>|
| Experimental: Dose 6, Multiple dose<br>High dose | Drug: BI 113608<br>* High dose (Multiple dosing)<br>|
| Placebo Comparator: Placebo (Single dose)<br>Placebo | Drug: Placebo<br>* Placebo (Single dosing)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of Subjects With Drug-related Adverse Events | Percentage of subjects with drug-related adverse events (AE) in the SRD and MRD periods combined. The investigator assessed the possible causal relationship between an AE and the trial medication. | Up to 21 days (4 days for SRD period and 17 days for MRD period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Maximum Measured Concentration of the Analyte in Plasma) | maximum measured concentration of the analyte in plasma after a single dose of BI 113608. | 0.25 hours (h), 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 71.75h after drug administration | 
| Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | Time from dosing to maximum measured concentration in plasma after a single dose of BI 113608. | 0.25 hours (h), 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 71.75h after drug administration | 
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity after a single dose of BI 113608. | 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 71.75h after drug administration | 
| AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | Area under the concentration-time curve of the analyte in plasma from time 0 to time of last quantifiable data point after a single dose of BI 113608. | 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 71.75h after drug administration | 
| t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | Terminal half-life of the analyte in plasma after a single dose of BI 113608. | 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 71.75h after drug administration | 
| Cmax,ss | Maximum measured concentration of the analyte in plasma at steady state | 23.92h, 71.92h, 119.92h, 167.92h, 215.92h, 227.92h, 263.92h, 275.92h, 311.92h, 312.25h, 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h, 348h, 360h, 384h | 
| Tmax,ss | Time from last dosing to maximum concentration of the analyte in plasma at steady state | 23.92h, 71.92h, 119.92h, 167.92h, 215.92h, 227.92h, 263.92h, 275.92h, 311.92h, 312.25h, 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h, 348h, 360h, 384h | 
| AUCtau,ss | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval tau | 23.92h, 71.92h, 119.92h, 167.92h, 215.92h, 227.92h, 263.92h, 275.92h, 311.92h, 312.25h, 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h, 348h, 360h, 384h | 
| t1/2,ss | Terminal half-life of the analyte in plasma at steady state | 23.92h, 71.92h, 119.92h, 167.92h, 215.92h, 227.92h, 263.92h, 275.92h, 311.92h, 312.25h, 312.5h, 312.75h, 313h, 313.5h, 314h, 314.5h, 315h, 316h, 318h, 320h, 322h, 324h, 328h, 336h, 348h, 360h, 384h | 
| RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | Accumulation ratio of the analyte in plasma at steady state after multiple oral administration over a uniform dosing interval tau, expressed as ratio of Cmax at steady state and after single dose | 0.25h,0.5h,0.75h,1h,1.5h,2h,2.5h,3h,4h,6h,8h,10h,12h,16h,24h,36h,48h, 72h in SRD and  24h, 72h, 120h, 168h, 216h, 228h, 264h, 276h, 312h, 312.25h,312.5h,312.75h,313h,313.5h,314h,314.5h,315h,316h,318h,320h,322h,324h,328h,336h,348h,360h,384h in MRD | 
| RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | Accumulation ratio of the analyte in plasma at steady state after multiple dose administration over a uniform dosing interval tau, expressed as ratio of AUC at steady state and after single dose | 0.25h,0.5h,0.75h,1h,1.5h,2h,2.5h,3h,4h,6h,8h,10h,12h,16h,24h,36h,48h, 72h in SRD and  24h, 72h, 120h, 168h, 216h, 228h, 264h, 276h, 312h, 312.25h,312.5h,312.75h,313h,313.5h,314h,314.5h,315h,316h,318h,320h,322h,324h,328h,336h,348h,360h,384h in MRD |