Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 691751 in Healthy Asian Male Volunteers

Study Overview
=================
Brief Summary
-----------------
BI 691751 is currently being developed to inhibit growth and prevent rupture of atherosclerotic plaques and to consequently reduce the risk of major cardiovascular events in patients with established atherosclerotic disease. 1334.5 is a Pan Asian Phase 1 study to investigate safety, tolerability and pharmacokinetics of BI 691751 in healthy Chinese and Japanese male volunteers.

Official Title
-----------------
Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 691751 in Healthy Asian Male Volunteers in a Randomised, Double-blind, Placebo-controlled Design.

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Placebo to BI 691751
* Drug: BI 691751 high dose
* Drug: BI 691751 middle dose
* Drug: Placebo to BI 691751
* Drug: BI 691751 low dose 1
* Drug: Placebo to BI 691751
* Drug: Placebo to BI 691751
* Drug: BI 691751 low dose 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Healthy males based upon a complete medical history, including a physical examination, vital signs (blood pressure, pulse rate), 12-lead ECG, and clinical laboratory tests Chinese ethnicity, Japanese ethnicity according to the following criteria: 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 Japanese; born in Japan and holding Japanese passport, have lived outside of Japan <10 years, and have parents and grandparents who were all born in Japan Age within the range of 20 to 45 years Body mass index within the range of 18.5 and 25 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation. Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator. Pulse rate outside the range of 50-90 bpm or blood pressure outside the ranges of 90-140 for systolic and 50-90 mmHg for diastolic blood pressure if confirmed by repeat measurement. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug Diseases of the central nervous system (such as epilepsy), central neurological disorders or psychiatric disorders History of relevant orthostatic hypotension, fainting spells, or blackouts Relevant chronic or acute infections History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients) Intake of drugs with a long half-life (greater than 24 hours) within 30 days or less than 10 half-lives of the respective drug prior to study drug administration Use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval within 14 days prior to study drug administration Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) Inability to refrain from smoking on specified trial days Alcohol abuse (consumption of more than30 g/day) Drug abuse or positive drug screen Blood donation (more than 100 mL within 30 days prior to administration of trial medication or intended 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 repeated demonstration of a QTc interval greater than 450 ms) or any other relevant ECG finding 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 by the investigator as unsuitable for inclusion, 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 691751 low dose 1<br>BI 691751 low dose 1 | Drug: Placebo to BI 691751<br>* Placebo to BI 691751<br>Drug: BI 691751 low dose 1<br>* BI 691751 low dose 1<br>|
| Experimental: BI 691751 low dose 2<br>BI 691751 low dose 2 | Drug: Placebo to BI 691751<br>* Placebo to BI 691751<br>Drug: BI 691751 low dose 2<br>* BI 691751 low dose 2<br>|
| Experimental: BI 691751 middle dose<br>BI 691751 middle dose | Drug: BI 691751 middle dose<br>* BI 691751 middle dose<br>Drug: Placebo to BI 691751<br>* Placebo to BI 691751<br>|
| Experimental: BI 691751 high dose<br>BI 691751 high dose | Drug: Placebo to BI 691751<br>* Placebo to BI 691751<br>Drug: BI 691751 high dose<br>* BI 691751 high dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Drug Related Adverse Events | Percentage of participants with drug related adverse events (AEs) | From drug administration until 31 days after drug administration, 31 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Measured Concentration of the Analyte (Cmax) | Maximum measured concentration of the analyte in plasma/whole blood | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Maximum Measured Concentration of the Analyte (Cmax) - Overall | Maximum measured concentration of the analyte in plasma/whole blood for all participants (Chinese and Japanese) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Time from (last) dosing to the maximum measured concentration of the analyte in plasma/whole blood | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Time from (last) dosing to the maximum measured concentration of the analyte in plasma/whole blood for all participants (Chinese and Japanese) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 extrapolated to infinity (AUC0-infinity) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 extrapolated to infinity for all participants (Chinese and Japanese) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) - Overall | Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) for all participants (Chinese and Japanese) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Terminal Half-life of the Analyte (T1/2) | Terminal half-life (T1/2) of the analyte in plasma/whole blood | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration | 
| Terminal Half-life of the Analyte (T1/2) - Overall | Terminal half-life (T1/2) of the analyte in plasma/whole blood for all participants (Chinese and Japanese) | 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration |