Healthy
Conditions
Brief summary
Safety, tolerability and pharmacokinetics of single and multiple oral doses of BI 113608 in healthy Chinese, Japanese and Caucasian male volunteers.
Interventions
DRUGBI 113608
Medium dose (Multiple dosing)
DRUGPlacebo
Placebo (Multiple dosing)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number (%) of Subjects With Drug-related Adverse Events | Up to 21 days (4 days for SRD period and 17 days for MRD period) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 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 | Time from dosing to maximum measured concentration in plasma after a single dose of BI 113608. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 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 | 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. |
| AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 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 | 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. |
| t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 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 | Terminal half-life of the analyte in plasma after a single dose of BI 113608. |
| Cmax,ss | 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 | Maximum measured concentration of the analyte in plasma at steady state |
| Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 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 | maximum measured concentration of the analyte in plasma after a single dose of BI 113608. |
| AUCtau,ss | 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 | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval tau |
| t1/2,ss | 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 | Terminal half-life of the analyte in plasma at steady state |
| RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 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 | 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 |
| RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 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 | 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 |
| Tmax,ss | 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 | Time from last dosing to maximum concentration of the analyte in plasma at steady state |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo tablet: oral administration, single dose (single rising dose(SRD) period) followed by twice a day for 13 days plus a single dose on day 14 (MRD period) | 25 |
| BI 113608 - 10 mg 2 conventional tablets 5 mg BI 113608 oral administration, single dose (SRD period) followed by twice a day for 13 days plus a single dose on day 14 (MRD period) | 27 |
| BI 113608 - 25 mg 1 conventional tablet 25 mg BI 113608 oral administration, once daily (SRD period) followed by twice a day for 13 days plus a single dose on day 14 (MRD period) | 18 |
| BI 113608 - 50 mg 2 conventional tablets 25 mg BI 113608 oral administration, once daily (SRD period) followed by twice a day for 13 days plus a single dose on day 14 (MRD period) | 27 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Multiple Rising Dose (MRD) Period | Adverse Event | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | BI 113608 - 10 mg | BI 113608 - 25 mg | BI 113608 - 50 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 27.8 Years STANDARD_DEVIATION 5.1 | 28.5 Years STANDARD_DEVIATION 4.4 | 28.3 Years STANDARD_DEVIATION 6.4 | 28.5 Years STANDARD_DEVIATION 5.2 | 28.3 Years STANDARD_DEVIATION 5.2 |
| Gender Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 25 Participants | 27 Participants | 18 Participants | 27 Participants | 97 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 9 | 3 / 9 | 5 / 7 | 5 / 9 | 2 / 9 | 9 / 9 | 7 / 9 | 4 / 9 | 9 / 9 | 7 / 9 | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 7 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
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.
Time frame: Up to 21 days (4 days for SRD period and 17 days for MRD period)
Population: Treated set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number (%) of Subjects With Drug-related Adverse Events | 28.0 Percentage of participants |
| BI 113608 - 10 mg | Number (%) of Subjects With Drug-related Adverse Events | 51.9 Percentage of participants |
| BI 113608 - 25 mg | Number (%) of Subjects With Drug-related Adverse Events | 33.3 Percentage of participants |
| BI 113608 - 50 mg | Number (%) of Subjects With Drug-related Adverse Events | 92.6 Percentage of participants |
Secondary
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.
Time frame: 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
Population: The PK analysis set (PKS) included all subjects of the TS who provided at least 1 secondary PK endpoint in any dose period, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 199 nmol*h/L | Geometric Coefficient of Variation 39.6 |
| BI 113608 - 10 mg | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 288 nmol*h/L | Geometric Coefficient of Variation 26.8 |
| BI 113608 - 25 mg | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 196 nmol*h/L | Geometric Coefficient of Variation 20.1 |
| BI 113608 - 50 mg | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 648 nmol*h/L | Geometric Coefficient of Variation 29.9 |
| BI 113608 - 25 mg - Japanese | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 775 nmol*h/L | Geometric Coefficient of Variation 28.7 |
| BI 113608 - 50 mg - Chinese | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 1560 nmol*h/L | Geometric Coefficient of Variation 23.1 |
| BI 113608 - 50 mg - Japanese | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 1320 nmol*h/L | Geometric Coefficient of Variation 48.7 |
| BI 113608 - 50 mg - Caucasian | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) | 1410 nmol*h/L | Geometric Coefficient of Variation 21 |
Secondary
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.
Time frame: 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
Population: The PK analysis set (PKS) included all subjects of the TS who provided at least 1 secondary PK endpoint in any dose period, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 197 nmol*h/L | Geometric Coefficient of Variation 39.9 |
| BI 113608 - 10 mg | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 285 nmol*h/L | Geometric Coefficient of Variation 27.2 |
| BI 113608 - 25 mg | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 193 nmol*h/L | Geometric Coefficient of Variation 19.8 |
| BI 113608 - 50 mg | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 645 nmol*h/L | Geometric Coefficient of Variation 30.4 |
| BI 113608 - 25 mg - Japanese | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 773 nmol*h/L | Geometric Coefficient of Variation 28.7 |
| BI 113608 - 50 mg - Chinese | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 1560 nmol*h/L | Geometric Coefficient of Variation 23.2 |
| BI 113608 - 50 mg - Japanese | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 1320 nmol*h/L | Geometric Coefficient of Variation 48.9 |
| BI 113608 - 50 mg - Caucasian | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma From Time 0 to Time of Last Quantifiable Data Point) | 1400 nmol*h/L | Geometric Coefficient of Variation 20.9 |
Secondary
AUCtau,ss
Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval tau
Time frame: 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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUCtau,ss | 222 nmol*h/L | Geometric Coefficient of Variation 26.9 |
| BI 113608 - 10 mg | AUCtau,ss | 273 nmol*h/L | Geometric Coefficient of Variation 35.7 |
| BI 113608 - 25 mg | AUCtau,ss | 199 nmol*h/L | Geometric Coefficient of Variation 31.7 |
| BI 113608 - 50 mg | AUCtau,ss | 860 nmol*h/L | Geometric Coefficient of Variation 33.4 |
| BI 113608 - 25 mg - Japanese | AUCtau,ss | 823 nmol*h/L | Geometric Coefficient of Variation 20.5 |
| BI 113608 - 50 mg - Chinese | AUCtau,ss | 2000 nmol*h/L | Geometric Coefficient of Variation 6.46 |
| BI 113608 - 50 mg - Japanese | AUCtau,ss | 1560 nmol*h/L | Geometric Coefficient of Variation 22 |
| BI 113608 - 50 mg - Caucasian | AUCtau,ss | 1530 nmol*h/L | Geometric Coefficient of Variation 41.5 |
Secondary
Cmax (Maximum Measured Concentration of the Analyte in Plasma)
maximum measured concentration of the analyte in plasma after a single dose of BI 113608.
Time frame: 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
Population: The PK analysis set (PKS) included all subjects of the TS who provided at least 1 secondary PK endpoint in any dose period, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 45.8 nmol/L | Geometric Coefficient of Variation 71.4 |
| BI 113608 - 10 mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 72.7 nmol/L | Geometric Coefficient of Variation 63.6 |
| BI 113608 - 25 mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 38.9 nmol/L | Geometric Coefficient of Variation 40.1 |
| BI 113608 - 50 mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 191 nmol/L | Geometric Coefficient of Variation 55.8 |
| BI 113608 - 25 mg - Japanese | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 217 nmol/L | Geometric Coefficient of Variation 37.2 |
| BI 113608 - 50 mg - Chinese | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 494 nmol/L | Geometric Coefficient of Variation 36.8 |
| BI 113608 - 50 mg - Japanese | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 320 nmol/L | Geometric Coefficient of Variation 71.4 |
| BI 113608 - 50 mg - Caucasian | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 437 nmol/L | Geometric Coefficient of Variation 28.7 |
Secondary
Cmax,ss
Maximum measured concentration of the analyte in plasma at steady state
Time frame: 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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss | 42.5 nmol/L | Geometric Coefficient of Variation 66.4 |
| BI 113608 - 10 mg | Cmax,ss | 66.5 nmol/L | Geometric Coefficient of Variation 54.1 |
| BI 113608 - 25 mg | Cmax,ss | 33.7 nmol/L | Geometric Coefficient of Variation 48.2 |
| BI 113608 - 50 mg | Cmax,ss | 223 nmol/L | Geometric Coefficient of Variation 56.7 |
| BI 113608 - 25 mg - Japanese | Cmax,ss | 234 nmol/L | Geometric Coefficient of Variation 33.2 |
| BI 113608 - 50 mg - Chinese | Cmax,ss | 500 nmol/L | Geometric Coefficient of Variation 19 |
| BI 113608 - 50 mg - Japanese | Cmax,ss | 409 nmol/L | Geometric Coefficient of Variation 43.2 |
| BI 113608 - 50 mg - Caucasian | Cmax,ss | 407 nmol/L | Geometric Coefficient of Variation 27 |
Secondary
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
Time frame: 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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.32 Ratio of AUC | Geometric Coefficient of Variation 23.4 |
| BI 113608 - 10 mg | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.11 Ratio of AUC | Geometric Coefficient of Variation 14.4 |
| BI 113608 - 25 mg | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.27 Ratio of AUC | Geometric Coefficient of Variation 18.1 |
| BI 113608 - 50 mg | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.49 Ratio of AUC | Geometric Coefficient of Variation 23.7 |
| BI 113608 - 25 mg - Japanese | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.19 Ratio of AUC | Geometric Coefficient of Variation 18.6 |
| BI 113608 - 50 mg - Chinese | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.42 Ratio of AUC | Geometric Coefficient of Variation 22.3 |
| BI 113608 - 50 mg - Japanese | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.47 Ratio of AUC | Geometric Coefficient of Variation 32.8 |
| BI 113608 - 50 mg - Caucasian | RA,AUC (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Dose Administration Over a Uniform Dosing Interval Tau) | 1.21 Ratio of AUC | Geometric Coefficient of Variation 45 |
Secondary
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
Time frame: 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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 0.928 Ratio of Cmax | Geometric Coefficient of Variation 52.2 |
| BI 113608 - 10 mg | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 0.915 Ratio of Cmax | Geometric Coefficient of Variation 31.4 |
| BI 113608 - 25 mg | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 0.866 Ratio of Cmax | Geometric Coefficient of Variation 34.1 |
| BI 113608 - 50 mg | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 1.17 Ratio of Cmax | Geometric Coefficient of Variation 61.2 |
| BI 113608 - 25 mg - Japanese | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 1.08 Ratio of Cmax | Geometric Coefficient of Variation 37.2 |
| BI 113608 - 50 mg - Chinese | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 1.01 Ratio of Cmax | Geometric Coefficient of Variation 23.6 |
| BI 113608 - 50 mg - Japanese | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 1.39 Ratio of Cmax | Geometric Coefficient of Variation 64.4 |
| BI 113608 - 50 mg - Caucasian | RA,Cmax (Accumulation Ratio of the Analyte in Plasma at Steady State After Multiple Oral Administration Over a Uniform Dosing Interval Tau) | 0.931 Ratio of Cmax | Geometric Coefficient of Variation 36.1 |
Secondary
t1/2,ss
Terminal half-life of the analyte in plasma at steady state
Time frame: 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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | t1/2,ss | 13.6 hours | Geometric Coefficient of Variation 10.4 |
| BI 113608 - 10 mg | t1/2,ss | 15.3 hours | Geometric Coefficient of Variation 25.1 |
| BI 113608 - 25 mg | t1/2,ss | 16.6 hours | Geometric Coefficient of Variation 51 |
| BI 113608 - 50 mg | t1/2,ss | 13.2 hours | Geometric Coefficient of Variation 23.3 |
| BI 113608 - 25 mg - Japanese | t1/2,ss | 13.1 hours | Geometric Coefficient of Variation 9.43 |
| BI 113608 - 50 mg - Chinese | t1/2,ss | 13.4 hours | Geometric Coefficient of Variation 16.8 |
| BI 113608 - 50 mg - Japanese | t1/2,ss | 12.4 hours | Geometric Coefficient of Variation 6.97 |
| BI 113608 - 50 mg - Caucasian | t1/2,ss | 13.7 hours | Geometric Coefficient of Variation 35.8 |
Secondary
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.
Time frame: 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
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 12.7 hours | Geometric Coefficient of Variation 45 |
| BI 113608 - 10 mg | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 12.1 hours | Geometric Coefficient of Variation 29.3 |
| BI 113608 - 25 mg | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 15.4 hours | Geometric Coefficient of Variation 33.2 |
| BI 113608 - 50 mg | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 11.7 hours | Geometric Coefficient of Variation 29.8 |
| BI 113608 - 25 mg - Japanese | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 10.1 hours | Geometric Coefficient of Variation 23 |
| BI 113608 - 50 mg - Chinese | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 11.7 hours | Geometric Coefficient of Variation 18.2 |
| BI 113608 - 50 mg - Japanese | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 10.7 hours | Geometric Coefficient of Variation 15.3 |
| BI 113608 - 50 mg - Caucasian | t1/2 (Terminal Half-life of the Analyte in Plasma After the First Dose) | 12.9 hours | Geometric Coefficient of Variation 21.8 |
Secondary
Tmax,ss
Time from last dosing to maximum concentration of the analyte in plasma at steady state
Time frame: 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
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax,ss | 0.75 hours |
| BI 113608 - 10 mg | Tmax,ss | 0.75 hours |
| BI 113608 - 25 mg | Tmax,ss | 1.00 hours |
| BI 113608 - 50 mg | Tmax,ss | 0.75 hours |
| BI 113608 - 25 mg - Japanese | Tmax,ss | 0.75 hours |
| BI 113608 - 50 mg - Chinese | Tmax,ss | 0.75 hours |
| BI 113608 - 50 mg - Japanese | Tmax,ss | 0.767 hours |
| BI 113608 - 50 mg - Caucasian | Tmax,ss | 0.75 hours |
Secondary
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.
Time frame: 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
Population: The PK analysis set (PKS) included all subjects of the TS who provided at least 1 secondary PK endpoint in any dose period, which was judged as PK evaluable and was not affected by important protocol violation(s) relevant to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 1.00 hour |
| BI 113608 - 10 mg | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.75 hour |
| BI 113608 - 25 mg | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.75 hour |
| BI 113608 - 50 mg | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.50 hour |
| BI 113608 - 25 mg - Japanese | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.75 hour |
| BI 113608 - 50 mg - Chinese | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.50 hour |
| BI 113608 - 50 mg - Japanese | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.75 hour |
| BI 113608 - 50 mg - Caucasian | Tmax (Time From Dosing to Maximum Measured Concentration in Plasma) | 0.75 hour |