Healthy
Conditions
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.
Interventions
DRUGPlacebo to BI 691751
Placebo to BI 691751
DRUGBI 691751 high dose
BI 691751 high dose
DRUGBI 691751 middle dose
BI 691751 middle dose
DRUGBI 691751 low dose 1
BI 691751 low dose 1
DRUGBI 691751 low dose 2
BI 691751 low dose 2
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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 2. 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 3. Age within the range of 20 to 45 years 4. Body mass index within the range of 18.5 and 25 kg/m2 5. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.
Exclusion criteria
1. 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. 2. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 3. Any evidence of a concomitant disease judged clinically relevant by the investigator 4. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 5. Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug 6. Diseases of the central nervous system (such as epilepsy), central neurological disorders or psychiatric disorders 7. History of relevant orthostatic hypotension, fainting spells, or blackouts 8. Relevant chronic or acute infections 9. History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients) 10. 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 11. 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 12. Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication 13. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) 14. Inability to refrain from smoking on specified trial days 15. Alcohol abuse (consumption of more than30 g/day) 16. Drug abuse or positive drug screen 17. Blood donation (more than 100 mL within 30 days prior to administration of trial medication or intended during the trial) 18. Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial 19. Inability to comply with dietary regimen of trial site 20. 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 21. A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) 22. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug Related Adverse Events | From drug administration until 31 days after drug administration, 31 days | Percentage of participants with drug related adverse events (AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of the Analyte (Cmax) - Overall | 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 in plasma/whole blood for all participants (Chinese and Japanese) |
| Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | 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 (last) dosing to the maximum measured concentration of the analyte in plasma/whole blood |
| Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | 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 (last) dosing to the maximum measured concentration of the analyte in plasma/whole blood for all participants (Chinese and Japanese) |
| Area Under the Concentration-time Curve of the Analyte 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 in plasma/whole blood over the time interval from 0 extrapolated to infinity (AUC0-infinity) |
| Maximum Measured Concentration of the Analyte (Cmax) | 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 in plasma/whole blood |
| 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) | 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 in plasma/whole blood over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) |
| Terminal Half-life of the Analyte (T1/2) - Overall | 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 (T1/2) of the analyte in plasma/whole blood for all participants (Chinese and Japanese) |
| 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 | 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 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) |
| Terminal Half-life of the Analyte (T1/2) | 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 (T1/2) of the analyte in plasma/whole blood |
| Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | 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 in plasma/whole blood over the time interval from 0 extrapolated to infinity for all participants (Chinese and Japanese) |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chinese: Placebo Chinese participants received a single placebo tablet matching the BI 691751 tablets, orally with 240 mL water after an overnight fast of at least 10 hours. | 8 |
| Chinese: BI 691751 5mg Chinese participants received a single tablet of BI 691751 5mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Chinese: BI 691751 10mg Chinese participants received a single tablet of BI 691751 10mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Chinese: BI 691751 30mg Chinese participants received a single tablet of BI 691751 30mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Chinese: BI 691751 60mg Chinese participants received a single tablet of BI 691751 60mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Japanese: Placebo Japanese participants received a single placebo tablet matching the BI 691751 tablets, orally with 240 mL water after an overnight fast of at least 10 hours. | 8 |
| Japanese: BI 691751 5mg Japanese participants received a single tablet of BI 691751 5mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Japanese: BI 691751 10mg Japanese participants received a single tablet of BI 691751 10mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Japanese: BI 691751 30mg Japanese participants received a single tablet of BI 691751 30mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Japanese: BI 691751 60mg Japanese participants received a single tablet of BI 691751 60mg orally with 240 mL water after an overnight fast of at least 10 hours. | 6 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Chinese: Placebo | Chinese: BI 691751 5mg | Chinese: BI 691751 10mg | Chinese: BI 691751 30mg | Chinese: BI 691751 60mg | Japanese: Placebo | Japanese: BI 691751 5mg | Japanese: BI 691751 10mg | Japanese: BI 691751 30mg | Japanese: BI 691751 60mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 25.3 Years STANDARD_DEVIATION 5.06 | 24.5 Years STANDARD_DEVIATION 3.73 | 23.0 Years STANDARD_DEVIATION 2.53 | 26.3 Years STANDARD_DEVIATION 4.55 | 28.8 Years STANDARD_DEVIATION 4.02 | 29.5 Years STANDARD_DEVIATION 3.82 | 31.7 Years STANDARD_DEVIATION 4.76 | 36.5 Years STANDARD_DEVIATION 2.74 | 31.0 Years STANDARD_DEVIATION 4.82 | 34.5 Years STANDARD_DEVIATION 0.84 | 29.0 Years STANDARD_DEVIATION 5.52 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 6 / 12 | 4 / 12 | 3 / 12 | 7 / 12 |
| serious Total, serious adverse events | 0 / 16 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percentage of Participants With Drug Related Adverse Events
Percentage of participants with drug related adverse events (AEs)
Time frame: From drug administration until 31 days after drug administration, 31 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chinese: Placebo | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Chinese: BI 691751 5mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Chinese: BI 691751 10mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Chinese: BI 691751 30mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Chinese: BI 691751 60mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Japanese: Placebo | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Japanese: BI 691751 5mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Japanese: BI 691751 10mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Japanese: BI 691751 30mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
| Japanese: BI 691751 60mg | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
Secondary
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)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | NA nmol*h/L | — |
| Chinese: Placebo | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 31600 nmol*h/L | Geometric Coefficient of Variation 23.3 |
| Chinese: BI 691751 5mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | 5280 nmol*h/L | Geometric Coefficient of Variation 17.3 |
| Chinese: BI 691751 5mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 51800 nmol*h/L | Geometric Coefficient of Variation 22.4 |
| Chinese: BI 691751 10mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | 18000 nmol*h/L | Geometric Coefficient of Variation 22.3 |
| Chinese: BI 691751 10mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 75600 nmol*h/L | Geometric Coefficient of Variation 13.5 |
| Chinese: BI 691751 30mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | 37400 nmol*h/L | Geometric Coefficient of Variation 23.9 |
| Chinese: BI 691751 30mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 118000 nmol*h/L | Geometric Coefficient of Variation 10.3 |
| Chinese: BI 691751 60mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | NA nmol*h/L | — |
| Chinese: BI 691751 60mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 35600 nmol*h/L | Geometric Coefficient of Variation 65.5 |
| Japanese: Placebo | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | NA nmol*h/L | — |
| Japanese: Placebo | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 48700 nmol*h/L | Geometric Coefficient of Variation 19.6 |
| Japanese: BI 691751 5mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 91800 nmol*h/L | Geometric Coefficient of Variation 38.6 |
| Japanese: BI 691751 5mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | 22400 nmol*h/L | Geometric Coefficient of Variation 28 |
| Japanese: BI 691751 10mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Plasma (N=0,5,6,6,0,0,6,6) | 42000 nmol*h/L | Geometric Coefficient of Variation 14.1 |
| Japanese: BI 691751 10mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | Blood (N=5,6,6,6,6,6,6,6) | 105000 nmol*h/L | Geometric Coefficient of Variation 11.4 |
Secondary
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)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Plasma (N=0, 8, 12, 12) | NA nmol*h/L | — |
| Chinese: Placebo | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Blood (N=11, 12, 12, 12) | 33800 nmol*h/L | Geometric Coefficient of Variation 47.5 |
| Chinese: BI 691751 5mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Blood (N=11, 12, 12, 12) | 50200 nmol*h/L | Geometric Coefficient of Variation 20.4 |
| Chinese: BI 691751 5mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Plasma (N=0, 8, 12, 12) | 5210 nmol*h/L | Geometric Coefficient of Variation 27.8 |
| Chinese: BI 691751 10mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Plasma (N=0, 8, 12, 12) | 20100 nmol*h/L | Geometric Coefficient of Variation 26.8 |
| Chinese: BI 691751 10mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Blood (N=11, 12, 12, 12) | 83300 nmol*h/L | Geometric Coefficient of Variation 29.2 |
| Chinese: BI 691751 30mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Plasma (N=0, 8, 12, 12) | 39600 nmol*h/L | Geometric Coefficient of Variation 19.6 |
| Chinese: BI 691751 30mg | Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall | Blood (N=11, 12, 12, 12) | 112000 nmol*h/L | Geometric Coefficient of Variation 12.1 |
Secondary
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)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | 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) | Plasma | 1320 nmol*h/L | Geometric Coefficient of Variation 22.1 |
| Chinese: Placebo | 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) | Blood | 19200 nmol*h/L | Geometric Coefficient of Variation 11.9 |
| Chinese: BI 691751 5mg | 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) | Plasma | 4720 nmol*h/L | Geometric Coefficient of Variation 17.8 |
| Chinese: BI 691751 5mg | 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) | Blood | 27900 nmol*h/L | Geometric Coefficient of Variation 9.9 |
| Chinese: BI 691751 10mg | 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) | Plasma | 17500 nmol*h/L | Geometric Coefficient of Variation 23.1 |
| Chinese: BI 691751 10mg | 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) | Blood | 41000 nmol*h/L | Geometric Coefficient of Variation 14.6 |
| Chinese: BI 691751 30mg | 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) | Plasma | 37000 nmol*h/L | Geometric Coefficient of Variation 24.2 |
| Chinese: BI 691751 30mg | 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) | Blood | 66600 nmol*h/L | Geometric Coefficient of Variation 14.2 |
| Chinese: BI 691751 60mg | 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) | Plasma | 1310 nmol*h/L | Geometric Coefficient of Variation 27.3 |
| Chinese: BI 691751 60mg | 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) | Blood | 19500 nmol*h/L | Geometric Coefficient of Variation 22.2 |
| Japanese: Placebo | 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) | Plasma | 5060 nmol*h/L | Geometric Coefficient of Variation 38.7 |
| Japanese: Placebo | 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) | Blood | 29600 nmol*h/L | Geometric Coefficient of Variation 11.1 |
| Japanese: BI 691751 5mg | 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) | Blood | 48300 nmol*h/L | Geometric Coefficient of Variation 16.2 |
| Japanese: BI 691751 5mg | 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) | Plasma | 21600 nmol*h/L | Geometric Coefficient of Variation 28.6 |
| Japanese: BI 691751 10mg | 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) | Plasma | 41100 nmol*h/L | Geometric Coefficient of Variation 13.8 |
| Japanese: BI 691751 10mg | 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) | Blood | 66800 nmol*h/L | Geometric Coefficient of Variation 9.5 |
Secondary
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)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | 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 | Plasma (N=10, 12, 12, 12) | 1310 nmol*h/L | Geometric Coefficient of Variation 23.9 |
| Chinese: Placebo | 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 | Blood (N=10, 12, 12, 12) | 19400 nmol*h/L | Geometric Coefficient of Variation 17.9 |
| Chinese: BI 691751 5mg | 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 | Plasma (N=10, 12, 12, 12) | 4890 nmol*h/L | Geometric Coefficient of Variation 28.7 |
| Chinese: BI 691751 5mg | 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 | Blood (N=10, 12, 12, 12) | 28700 nmol*h/L | Geometric Coefficient of Variation 10.5 |
| Chinese: BI 691751 10mg | 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 | Blood (N=10, 12, 12, 12) | 44500 nmol*h/L | Geometric Coefficient of Variation 17.1 |
| Chinese: BI 691751 10mg | 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 | Plasma (N=10, 12, 12, 12) | 19500 nmol*h/L | Geometric Coefficient of Variation 27.2 |
| Chinese: BI 691751 30mg | 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 | Blood (N=10, 12, 12, 12) | 66700 nmol*h/L | Geometric Coefficient of Variation 11.5 |
| Chinese: BI 691751 30mg | 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 | Plasma (N=10, 12, 12, 12) | 39000 nmol*h/L | Geometric Coefficient of Variation 19.6 |
Secondary
Maximum Measured Concentration of the Analyte (Cmax)
Maximum measured concentration of the analyte in plasma/whole blood
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 175 nmol/L | Geometric Coefficient of Variation 45.7 |
| Chinese: Placebo | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 247 nmol/L | Geometric Coefficient of Variation 21.5 |
| Chinese: BI 691751 5mg | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 477 nmol/L | Geometric Coefficient of Variation 25.5 |
| Chinese: BI 691751 5mg | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 523 nmol/L | Geometric Coefficient of Variation 19.7 |
| Chinese: BI 691751 10mg | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 1450 nmol/L | Geometric Coefficient of Variation 19.4 |
| Chinese: BI 691751 10mg | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 1490 nmol/L | Geometric Coefficient of Variation 22.1 |
| Chinese: BI 691751 30mg | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 3690 nmol/L | Geometric Coefficient of Variation 20.5 |
| Chinese: BI 691751 30mg | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 3470 nmol/L | Geometric Coefficient of Variation 16.4 |
| Chinese: BI 691751 60mg | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 129 nmol/L | Geometric Coefficient of Variation 33.2 |
| Chinese: BI 691751 60mg | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 213 nmol/L | Geometric Coefficient of Variation 17.9 |
| Japanese: Placebo | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 421 nmol/L | Geometric Coefficient of Variation 53.4 |
| Japanese: Placebo | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 509 nmol/L | Geometric Coefficient of Variation 35.4 |
| Japanese: BI 691751 5mg | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 1530 nmol/L | Geometric Coefficient of Variation 22.4 |
| Japanese: BI 691751 5mg | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 1520 nmol/L | Geometric Coefficient of Variation 18.1 |
| Japanese: BI 691751 10mg | Maximum Measured Concentration of the Analyte (Cmax) | Plasma | 4270 nmol/L | Geometric Coefficient of Variation 9.4 |
| Japanese: BI 691751 10mg | Maximum Measured Concentration of the Analyte (Cmax) | Blood | 3600 nmol/L | Geometric Coefficient of Variation 12.4 |
Secondary
Maximum Measured Concentration of the Analyte (Cmax) - Overall
Maximum measured concentration of the analyte in plasma/whole blood for all participants (Chinese and Japanese)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Plasma | 150 nmol/L | Geometric Coefficient of Variation 41.4 |
| Chinese: Placebo | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Blood | 229 nmol/L | Geometric Coefficient of Variation 20.4 |
| Chinese: BI 691751 5mg | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Blood | 516 nmol/L | Geometric Coefficient of Variation 27.2 |
| Chinese: BI 691751 5mg | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Plasma | 448 nmol/L | Geometric Coefficient of Variation 39.8 |
| Chinese: BI 691751 10mg | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Plasma | 1490 nmol/L | Geometric Coefficient of Variation 18 |
| Chinese: BI 691751 10mg | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Blood | 1510 nmol/L | Geometric Coefficient of Variation 21.2 |
| Chinese: BI 691751 30mg | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Plasma | 3970 nmol/L | Geometric Coefficient of Variation 17 |
| Chinese: BI 691751 30mg | Maximum Measured Concentration of the Analyte (Cmax) - Overall | Blood | 3530 nmol/L | Geometric Coefficient of Variation 14 |
Secondary
Terminal Half-life of the Analyte (T1/2)
Terminal half-life (T1/2) of the analyte in plasma/whole blood
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | NA hours | — |
| Chinese: Placebo | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 243 hours | Geometric Coefficient of Variation 40.6 |
| Chinese: BI 691751 5mg | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | 94.6 hours | Geometric Coefficient of Variation 29.8 |
| Chinese: BI 691751 5mg | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 333 hours | Geometric Coefficient of Variation 30.6 |
| Chinese: BI 691751 10mg | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | 102 hours | Geometric Coefficient of Variation 34.3 |
| Chinese: BI 691751 10mg | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 393 hours | Geometric Coefficient of Variation 23.1 |
| Chinese: BI 691751 30mg | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | 73.5 hours | Geometric Coefficient of Variation 40.4 |
| Chinese: BI 691751 30mg | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 417 hours | Geometric Coefficient of Variation 23.7 |
| Chinese: BI 691751 60mg | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | NA hours | — |
| Chinese: BI 691751 60mg | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 290 hours | Geometric Coefficient of Variation 62.8 |
| Japanese: Placebo | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | NA hours | — |
| Japanese: Placebo | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 265 hours | Geometric Coefficient of Variation 26.2 |
| Japanese: BI 691751 5mg | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 403 hours | Geometric Coefficient of Variation 48.9 |
| Japanese: BI 691751 5mg | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | 95.0 hours | Geometric Coefficient of Variation 64.7 |
| Japanese: BI 691751 10mg | Terminal Half-life of the Analyte (T1/2) | Plasma (N=0,5,6,6,0,0,6,6) | 89.9 hours | Geometric Coefficient of Variation 26.2 |
| Japanese: BI 691751 10mg | Terminal Half-life of the Analyte (T1/2) | Blood (N=5,6,6,6,6,6,6,6) | 340 hours | Geometric Coefficient of Variation 26 |
Secondary
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)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Terminal Half-life of the Analyte (T1/2) - Overall | Blood (N=11, 12, 12, 12) | 267 hours | Geometric Coefficient of Variation 51.6 |
| Chinese: Placebo | Terminal Half-life of the Analyte (T1/2) - Overall | Plasma (N=0, 8, 12, 12) | NA hours | — |
| Chinese: BI 691751 5mg | Terminal Half-life of the Analyte (T1/2) - Overall | Plasma (N=0, 8, 12, 12) | 84.2 hours | Geometric Coefficient of Variation 28.9 |
| Chinese: BI 691751 5mg | Terminal Half-life of the Analyte (T1/2) - Overall | Blood (N=11, 12, 12, 12) | 297 hours | Geometric Coefficient of Variation 29.8 |
| Chinese: BI 691751 10mg | Terminal Half-life of the Analyte (T1/2) - Overall | Blood (N=11, 12, 12, 12) | 398 hours | Geometric Coefficient of Variation 35.9 |
| Chinese: BI 691751 10mg | Terminal Half-life of the Analyte (T1/2) - Overall | Plasma (N=0, 8, 12, 12) | 98.4 hours | Geometric Coefficient of Variation 48.4 |
| Chinese: BI 691751 30mg | Terminal Half-life of the Analyte (T1/2) - Overall | Blood (N=11, 12, 12, 12) | 377 hours | Geometric Coefficient of Variation 26.2 |
| Chinese: BI 691751 30mg | Terminal Half-life of the Analyte (T1/2) - Overall | Plasma (N=0, 8, 12, 12) | 81.3 hours | Geometric Coefficient of Variation 34.1 |
Secondary
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
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chinese: Placebo | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.333 hours |
| Chinese: Placebo | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.333 hours |
| Chinese: BI 691751 5mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.667 hours |
| Chinese: BI 691751 5mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.667 hours |
| Chinese: BI 691751 10mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.667 hours |
| Chinese: BI 691751 10mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.667 hours |
| Chinese: BI 691751 30mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.667 hours |
| Chinese: BI 691751 30mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.667 hours |
| Chinese: BI 691751 60mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.667 hours |
| Chinese: BI 691751 60mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.500 hours |
| Japanese: Placebo | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.500 hours |
| Japanese: Placebo | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.333 hours |
| Japanese: BI 691751 5mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.667 hours |
| Japanese: BI 691751 5mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.667 hours |
| Japanese: BI 691751 10mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Plasma | 0.667 hours |
| Japanese: BI 691751 10mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) | Blood | 0.667 hours |
Secondary
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)
Time frame: 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
Population: All subjects of the treated set with the pharmacokinetic (PK) parameter calculated.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chinese: Placebo | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Plasma | 0.500 hours | Full Range 41.4 |
| Chinese: Placebo | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Blood | 0.333 hours | Full Range 20.4 |
| Chinese: BI 691751 5mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Blood | 0.500 hours | Full Range 27.2 |
| Chinese: BI 691751 5mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Plasma | 0.667 hours | Full Range 39.8 |
| Chinese: BI 691751 10mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Plasma | 0.667 hours | Full Range 18 |
| Chinese: BI 691751 10mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Blood | 0.667 hours | Full Range 21.2 |
| Chinese: BI 691751 30mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Plasma | 0.667 hours | Full Range 17 |
| Chinese: BI 691751 30mg | Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall | Blood | 0.667 hours | Full Range 14 |