Healthy
Conditions
Brief summary
Safety, tolerability and pharmacokinetics of single and multiple oral doses of BI 409306 tablets in healthy Chinese and Japanese male volunteers of a known genotype as specified in the study protocol.
Interventions
DRUGPlacebo
Subjects received matching placebo to the BI-409306 (film-coated tablet/s), administered orally on day 1 for single dose (SD) segment and on day 3 to day 9 for multiple dose (MD) segment
DRUGBI-409306 25 milligram (mg) SD
Subjects received 25 mg single dose of BI-409306 (film-coated tablet/s), administered orally once on day 1
DRUGBI-409306 50 mg SD
Subjects received 50 mg single dose of BI-409306 (film-coated tablet/s), administered orally once on day 1
DRUGBI-409306 100 mg SD
Subjects received 100 mg single dose of BI-409306 (film-coated tablet/s), administered orally once on day 1
DRUGBI-409306 100 mg MD
Subjects received 100 mg multiple dose of BI-409306 (film-coated tablet/s), administered orally once on day 3 to day 9
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
1. Healthy male Chinese and Japanese volunteers 2. Age between 20 and 45 years 3. BMI between 18.5 and 25 kg/m2 (Body Mass Index) 4. Known genotype as specified in the study protocol 5. Subjects must be able to understand and comply with study requirements
Exclusion criteria
1\. Any deviation from healthy condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | From first drug administration until 11 days after last dose of study medication, up to 18 days. | Percentage (%) of subjects with drug-related adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Area under the concentration-time curve of a single dose of BI 409306 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity). |
| Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Area under the concentration-time curve of a single dose of BI 409306 in plasma over the time interval 0 to the last quantifiable data point (AUC0-tz). |
| Maximum Measured Concentration of the Metabolite CD 13896 in Plasma (Cmax) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Maximum measured concentration of the metabolite CD 13896 in plasma (Cmax) after single administration of BI 409306. |
| Maximum Measured Concentration of the Metabolite CD 14084 in Plasma (Cmax) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Maximum measured concentration of the metabolite CD 14084 in plasma (Cmax) after single administration of BI 409306. |
| Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Maximum measured concentration of a single dose of BI 409306 in plasma (Cmax). |
| Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Area under the concentration-time curve of the metabolite CD 14084 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity) after single administration of BI 409306. |
| Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Area under the concentration-time curve of the metabolite CD 13896 in plasma over the time interval 0 to the last quantifiable data point (AUC0-tz) after single administration of BI 409306. |
| Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Area under the concentration-time curve of the metabolite CD 14084 in plasma over the time interval 0 to the last quantifiable data point (AUC0-tz) after single administration of BI 409306. |
| Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration. | Area under the concentration-time curve of the metabolite CD 13896 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity) after single administration of BI 409306. |
Countries
South Korea
Participant flow
Recruitment details
This was randomised, placebo controlled and double-blind within dose groups, single dose (3 dose groups), multiple dose (1 dose group, 8-day treatment), single centre trial with healthy Chinese and Japanese male volunteers
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received matching placebo to the BI-409306 (film-coated tablet/s), administered orally on day 1 for single dose (SD) segment and on day 3 to day 9 for multiple dose (MD) segment | 15 |
| BI-409306 25 Milligram (mg) SD Subjects received 25 mg single dose of BI-409306 (film-coated tablet/s), administered orally once on day 1 | 11 |
| BI-409306 50 mg SD Subjects received 50 mg single dose of BI-409306 (film-coated tablet/s), administered orally once on day 1 | 11 |
| BI-409306 100 mg SD Subjects received 100 mg single dose of BI-409306 (film-coated tablet/s), administered orally once on day 1 | 19 |
| BI-409306 100 mg SD & MD Subjects received 100 mg multiple dose of BI-409306 (film-coated tablet/s), administered orally once on day 3 to day 9. A wash-out period of 48 hours was included before the second dose (first dose of multiple dose segment) was administered. Subjects were considered for both single dose (following first dose) and multiple dose purposes. | 6 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Single Dose Segment (Day 1) | Not Treated | 1 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | BI-409306 25 Milligram (mg) SD | Total | BI-409306 100 mg SD & MD | BI-409306 100 mg SD | Placebo | BI-409306 50 mg SD |
|---|---|---|---|---|---|---|
| Age, Continuous | 26.5 Years STANDARD_DEVIATION 4 | 26.4 Years STANDARD_DEVIATION 4.8 | 26.3 Years STANDARD_DEVIATION 2.9 | 27.4 Years STANDARD_DEVIATION 5.8 | 24.9 Years STANDARD_DEVIATION 3.1 | 26.6 Years STANDARD_DEVIATION 6.4 |
| Ethnicity Chinese | 5 Participants | 32 Participants | 0 Participants | 13 Participants | 8 Participants | 6 Participants |
| Ethnicity Japanese | 6 Participants | 30 Participants | 6 Participants | 6 Participants | 7 Participants | 5 Participants |
| Poor metaboliser (PM) / extensive metaboliser (EM) Extensive metaboliser (EM) | 11 Participants | 46 Participants | 0 Participants | 13 Participants | 11 Participants | 11 Participants |
| Poor metaboliser (PM) / extensive metaboliser (EM) Poor metaboliser (PM) | 0 Participants | 16 Participants | 6 Participants | 6 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 62 Participants | 6 Participants | 19 Participants | 15 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 62 Participants | 6 Participants | 19 Participants | 15 Participants | 11 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 15 | 1 / 11 | 5 / 11 | 11 / 19 | 5 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 15 | 0 / 11 | 0 / 11 | 0 / 19 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Percentage (%) of Subjects With Drug-related Adverse Events (AEs)
Percentage (%) of subjects with drug-related adverse events (AEs).
Time frame: From first drug administration until 11 days after last dose of study medication, up to 18 days.
Population: Treated Set (TS) included all randomised subjects who were documented to have received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | 13.3 Percentage of Participants |
| BI-409306 25 Milligram (mg) SD | Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | 9.1 Percentage of Participants |
| BI-409306 50 mg SD | Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | 36.4 Percentage of Participants |
| BI-409306 100 mg SD | Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | 57.9 Percentage of Participants |
| BI-409306 100 mg MD-PM | Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | 83.3 Percentage of Participants |
| BI-409306 100 mg SD-PM | Percentage (%) of Subjects With Drug-related Adverse Events (AEs) | 83.3 Percentage of Participants |
Secondary
Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of a single dose of BI 409306 in plasma over the time interval 0 to the last quantifiable data point (AUC0-tz).
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 375 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 67.8 |
| BI-409306 25 Milligram (mg) SD | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 1040 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 102 |
| BI-409306 50 mg SD | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 2020 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 106 |
| BI-409306 100 mg SD | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 7550 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 21.4 |
| BI-409306 100 mg MD-PM | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 504 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 24.8 |
| BI-409306 100 mg SD-PM | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 985 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 40.3 |
| BI-409306 100 mg - Japanese | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 2100 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 47.1 |
| BI-409306 100 mg SD & MD - Japanese (PM) | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz) | 8640 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 32.1 |
Comparison: Dose proportionality was assessed in Chinese subjects. For the power model perfect dose proportionality would correspond to a slope of 1.95% CI: [0.5078, 1.8952]
Comparison: Dose proportionality was assessed in Japanese subjects. For the power model perfect dose proportionality would correspond to a slope of 1.95% CI: [0.7133, 1.3469]
Secondary
Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Area under the concentration-time curve of a single dose of BI 409306 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity).
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. Only subjects with non missing values were included in the endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 376 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 67.7 |
| BI-409306 25 Milligram (mg) SD | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 1070 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 119 |
| BI-409306 50 mg SD | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 2020 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 106 |
| BI-409306 100 mg SD | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 7550 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 21.4 |
| BI-409306 100 mg MD-PM | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 504 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 24.7 |
| BI-409306 100 mg SD-PM | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 985 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 40.3 |
| BI-409306 100 mg - Japanese | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 2100 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 47.1 |
| BI-409306 100 mg SD & MD - Japanese (PM) | Area Under the Concentration-time Curve of a Single Dose of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 8650 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 32.1 |
Comparison: Dose proportionality was assessed in Chinese subjects. For the power model perfect dose proportionality would correspond to a slope of 1.95% CI: [0.4794, 1.9202]
Comparison: Dose proportionality was assessed in Japanese subjects. For the power model perfect dose proportionality would correspond to a slope of 1.95% CI: [0.7131, 1.3466]
Secondary
Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz).
Area under the concentration-time curve of the metabolite CD 13896 in plasma over the time interval 0 to the last quantifiable data point (AUC0-tz) after single administration of BI 409306.
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. As pre-specified in the protocol, metabolite analyses were only planned for the 100 mg extensive metabolizer groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | 1650 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 14.2 |
| BI-409306 25 Milligram (mg) SD | Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | 1510 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 15.6 |
Secondary
Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Area under the concentration-time curve of the metabolite CD 13896 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity) after single administration of BI 409306.
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. As pre-specified in the protocol, metabolite analyses were only planned for the 100 mg extensive metabolizer groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 1650 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 14.2 |
| BI-409306 25 Milligram (mg) SD | Area Under the Concentration-time Curve of the Metabolite CD 13896 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 1520 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 15.6 |
Secondary
Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz).
Area under the concentration-time curve of the metabolite CD 14084 in plasma over the time interval 0 to the last quantifiable data point (AUC0-tz) after single administration of BI 409306.
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. As pre-specified in the protocol, metabolite analyses were only planned for the 100 mg extensive metabolizer groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | 8670 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 10.8 |
| BI-409306 25 Milligram (mg) SD | Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval 0 to the Last Quantifiable Data Point (AUC0-tz). | 9060 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 14.6 |
Secondary
Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity)
Area under the concentration-time curve of the metabolite CD 14084 in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity) after single administration of BI 409306.
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. As pre-specified in the protocol, metabolite analyses were only planned for the 100 mg extensive metabolizer groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 8670 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 10.8 |
| BI-409306 25 Milligram (mg) SD | Area Under the Concentration-time Curve of the Metabolite CD 14084 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | 9060 nanomol (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 14.6 |
Secondary
Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax)
Maximum measured concentration of a single dose of BI 409306 in plasma (Cmax).
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 292 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 113 |
| BI-409306 25 Milligram (mg) SD | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 824 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 74.1 |
| BI-409306 50 mg SD | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 1970 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 77.8 |
| BI-409306 100 mg SD | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 4020 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 26.8 |
| BI-409306 100 mg MD-PM | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 496 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 26.5 |
| BI-409306 100 mg SD-PM | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 914 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 32.5 |
| BI-409306 100 mg - Japanese | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 3290 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 43 |
| BI-409306 100 mg SD & MD - Japanese (PM) | Maximum Measured Concentration of a Single Dose of BI 409306 in Plasma (Cmax) | 4510 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 26.8 |
Comparison: Dose proportionality was assessed in Chinese subjects. For the power model perfect dose proportionality would correspond to a slope of 1.95% CI: [0.7272, 2.0151]
Comparison: Dose proportionality was assessed in Japanese subjects. For the power model perfect dose proportionality would correspond to a slope of 1.95% CI: [1.0421, 1.6883]
Secondary
Maximum Measured Concentration of the Metabolite CD 13896 in Plasma (Cmax)
Maximum measured concentration of the metabolite CD 13896 in plasma (Cmax) after single administration of BI 409306.
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. As pre-specified in the protocol, metabolite analyses were only planned for the 100 mg extensive metabolizer groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of the Metabolite CD 13896 in Plasma (Cmax) | 926 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 30.9 |
| BI-409306 25 Milligram (mg) SD | Maximum Measured Concentration of the Metabolite CD 13896 in Plasma (Cmax) | 1080 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 24.5 |
Secondary
Maximum Measured Concentration of the Metabolite CD 14084 in Plasma (Cmax)
Maximum measured concentration of the metabolite CD 14084 in plasma (Cmax) after single administration of BI 409306.
Time frame: PK plasma samples: 2 hours before drug administration and 10, 20, 30, 45 minutes, 1, 1:30, 2, 2:30, 3, 4, 6, 8, 10, 12, 14, 24 hours for SD segment after drug administration.
Population: The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least one evaluable observation for at least one pharmacokinetic (PK) endpoint without Important protocol violation (IPV) that could potentially influence the results of PK measurements for determination of primary PK endpoints. As pre-specified in the protocol, metabolite analyses were only planned for the 100 mg extensive metabolizer groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of the Metabolite CD 14084 in Plasma (Cmax) | 3800 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 21.8 |
| BI-409306 25 Milligram (mg) SD | Maximum Measured Concentration of the Metabolite CD 14084 in Plasma (Cmax) | 4340 nanomol (nmol) / Litre (L) | Geometric Coefficient of Variation 16.9 |