Healthy
Conditions
Brief summary
The primary objective of the current study is to investigate the safety, tolerability and pharmacokinetics of BI 411034 in healthy male volunteers following oral administration of single rising doses. The secondary objective is to explore dose proportionality of BI 411034 in CYP2C19 (Cytochrome P450) genotyped extensive metabolisers (EM). Another objective is to compare the safety and pharmacokinetic profiles between two different groups of CYP2C19 genotyped subjects, extensive metabolisers (EM) and poor metabolisers (PM)
Interventions
DRUGBI 411034
Low dose solution for oral administration
DRUGPlacebo
Solution for oral administration
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Healthy male subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug Related AEs | From drug administration until end of trial examination, up to 13 days | Number of participants with drug related adverse events (AEs) |
| Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | From drug administration until end of trial examination, up to 13 days | Clinically relevant abnormalities for physical examinations, vital signs (blood pressure, pulse rate, oral body temperature, orthostasis test), 12-lead electrocardiogram (ECG) and clinical laboratory tests. Clinically relevant abnormalities are reported by the investigator as adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration (Cmax ) | 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration | Maximum measured concentration of the analyte (BI 411034) in plasma |
| Time to Maximum Measured Concentration (Tmax) | 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration | Time from dosing to maximum measured concentration |
| Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration | Area under the concentration-time curve of the analyte (BI 411034) in plasma over the time interval from 0 extrapolated to infinity |
| Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration | Amount of analyte (BI 411034) eliminated in urine from the time point 0h to time point 4h. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo EM A powder for oral solution in the same volume as the respective active medication group and participants who are extensive metabolisers (EM) | 14 |
| 2mg EM Single oral dose of 2mg of BI 411034 for participants who are extensive metabolisers | 6 |
| 8mg EM Single oral dose of 8mg of BI 411034 for participants who are extensive metabolisers | 6 |
| 20mg EM Single oral dose of 20mg of BI 411034 for participants who are extensive metabolisers | 6 |
| 40mg EM Single oral dose of 40mg of BI 411034 for participants who are extensive metabolisers | 6 |
| 80mg EM Single oral dose of 80mg of BI 411034 for participants who are extensive metabolisers | 6 |
| 150mg EM Single oral dose of 150mg of BI 411034 for participants who are extensive metabolisers | 6 |
| 250mg EM Single oral dose of 250mg of BI 411034 for participants who are extensive metabolisers | 6 |
| Placebo PM A powder for oral solution in the same volume as the respective active medication group and participants who are poor metabolisers (PM) | 1 |
| 20/60mg PM Single oral dose of 20/60mg of BI 411034 for participants who are poor metabolisers | 5 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Other reason not defined | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo EM | 2mg EM | 8mg EM | 20mg EM | 40mg EM | 80mg EM | 150mg EM | 250mg EM | Placebo PM | 20/60mg PM | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 6.3 | 35.5 years STANDARD_DEVIATION 9.9 | 39.8 years STANDARD_DEVIATION 4.3 | 38.8 years STANDARD_DEVIATION 8.7 | 38.3 years STANDARD_DEVIATION 8.2 | 39.5 years STANDARD_DEVIATION 3.1 | 32.7 years STANDARD_DEVIATION 5.4 | 43.8 years STANDARD_DEVIATION 6.7 | 31.0 years | 42.4 years STANDARD_DEVIATION 8.6 | 38.6 years STANDARD_DEVIATION 7.1 |
| 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 | 14 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 1 Participants | 5 Participants | 62 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 | 3 / 14 | 0 / 6 | 1 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 3 / 6 | 1 / 1 | 0 / 5 | 3 / 5 |
| serious Total, serious adverse events | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 1 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests
Clinically relevant abnormalities for physical examinations, vital signs (blood pressure, pulse rate, oral body temperature, orthostasis test), 12-lead electrocardiogram (ECG) and clinical laboratory tests. Clinically relevant abnormalities are reported by the investigator as adverse events (AEs).
Time frame: From drug administration until end of trial examination, up to 13 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 8mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 20mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 40mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 80mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 150mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 250mg EM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 20mg PM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 60mg PM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 20mg PM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
| 60mg PM | Clinically Relevant Abnormalities for Physical Examinations, Vital Signs, ECG, Laboratory Tests | 0 participants |
Primary
Number of Participants With Drug Related AEs
Number of participants with drug related adverse events (AEs)
Time frame: From drug administration until end of trial examination, up to 13 days
Population: Treated set which included all subjects who were administered trial medication and were documented to have taken the dose of investigational treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2mg EM | Number of Participants With Drug Related AEs | 1 participants |
| 8mg EM | Number of Participants With Drug Related AEs | 0 participants |
| 20mg EM | Number of Participants With Drug Related AEs | 0 participants |
| 40mg EM | Number of Participants With Drug Related AEs | 1 participants |
| 80mg EM | Number of Participants With Drug Related AEs | 1 participants |
| 150mg EM | Number of Participants With Drug Related AEs | 1 participants |
| 250mg EM | Number of Participants With Drug Related AEs | 2 participants |
| 20mg PM | Number of Participants With Drug Related AEs | 3 participants |
| 60mg PM | Number of Participants With Drug Related AEs | 0 participants |
| 20mg PM | Number of Participants With Drug Related AEs | 0 participants |
| 60mg PM | Number of Participants With Drug Related AEs | 2 participants |
Secondary
Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4)
Amount of analyte (BI 411034) eliminated in urine from the time point 0h to time point 4h.
Time frame: 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 77.6 nmol | Geometric Coefficient of Variation 50.3 |
| 8mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 290 nmol | Geometric Coefficient of Variation 22.1 |
| 20mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 530 nmol | Geometric Coefficient of Variation 38.2 |
| 40mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 860 nmol | Geometric Coefficient of Variation 34.1 |
| 80mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 2070 nmol | Geometric Coefficient of Variation 38.8 |
| 150mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 3390 nmol | Geometric Coefficient of Variation 44.6 |
| 250mg EM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 4520 nmol | Geometric Coefficient of Variation 25.9 |
| 20mg PM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 1220 nmol | Geometric Coefficient of Variation 30.3 |
| 60mg PM | Amount of Analyte Eliminated in Urine From 0h to 4h (Ae0-4) | 3080 nmol | Geometric Coefficient of Variation 22.1 |
Secondary
Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity)
Area under the concentration-time curve of the analyte (BI 411034) in plasma over the time interval from 0 extrapolated to infinity
Time frame: 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 134 nmol*h/L | Geometric Coefficient of Variation 54.3 |
| 8mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 729 nmol*h/L | Geometric Coefficient of Variation 96.4 |
| 20mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 1410 nmol*h/L | Geometric Coefficient of Variation 18.1 |
| 40mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 1900 nmol*h/L | Geometric Coefficient of Variation 66.2 |
| 80mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 6140 nmol*h/L | Geometric Coefficient of Variation 53.6 |
| 150mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 13300 nmol*h/L | Geometric Coefficient of Variation 70.6 |
| 250mg EM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 19700 nmol*h/L | Geometric Coefficient of Variation 47.7 |
| 20mg PM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 6240 nmol*h/L | Geometric Coefficient of Variation 14.8 |
| 60mg PM | Area Under the Curve From 0 Extrapolated to Infinity (AUC0-infinity) | 18500 nmol*h/L | Geometric Coefficient of Variation 13.1 |
Secondary
Maximum Measured Concentration (Cmax )
Maximum measured concentration of the analyte (BI 411034) in plasma
Time frame: 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration
Population: PK analysis set which included all subjects who were administered trial medication and were documented to have taken the dose of investigational treatment and who provided at least one observation for at least one pharmacokinetic (PK) endpoint without important protocol violations relevant to the evaluation of PK
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2mg EM | Maximum Measured Concentration (Cmax ) | 61.7 nmol/L | Geometric Coefficient of Variation 34 |
| 8mg EM | Maximum Measured Concentration (Cmax ) | 236 nmol/L | Geometric Coefficient of Variation 55.9 |
| 20mg EM | Maximum Measured Concentration (Cmax ) | 566 nmol/L | Geometric Coefficient of Variation 22 |
| 40mg EM | Maximum Measured Concentration (Cmax ) | 629 nmol/L | Geometric Coefficient of Variation 53.9 |
| 80mg EM | Maximum Measured Concentration (Cmax ) | 2630 nmol/L | Geometric Coefficient of Variation 38.8 |
| 150mg EM | Maximum Measured Concentration (Cmax ) | 4610 nmol/L | Geometric Coefficient of Variation 51.4 |
| 250mg EM | Maximum Measured Concentration (Cmax ) | 6600 nmol/L | Geometric Coefficient of Variation 15.3 |
| 20mg PM | Maximum Measured Concentration (Cmax ) | 935 nmol/L | Geometric Coefficient of Variation 17.1 |
| 60mg PM | Maximum Measured Concentration (Cmax ) | 2890 nmol/L | Geometric Coefficient of Variation 36.5 |
Secondary
Time to Maximum Measured Concentration (Tmax)
Time from dosing to maximum measured concentration
Time frame: 2 hours (h) before drug administration and 10 minutes (min), 20min, 30min, 45min, 1h 15min, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, and 72h after drug administration
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2mg EM | Time to Maximum Measured Concentration (Tmax) | 0.5 h |
| 8mg EM | Time to Maximum Measured Concentration (Tmax) | 0.63 h |
| 20mg EM | Time to Maximum Measured Concentration (Tmax) | 0.63 h |
| 40mg EM | Time to Maximum Measured Concentration (Tmax) | 1.00 h |
| 80mg EM | Time to Maximum Measured Concentration (Tmax) | 0.62 h |
| 150mg EM | Time to Maximum Measured Concentration (Tmax) | 0.62 h |
| 250mg EM | Time to Maximum Measured Concentration (Tmax) | 0.63 h |
| 20mg PM | Time to Maximum Measured Concentration (Tmax) | 0.75 h |
| 60mg PM | Time to Maximum Measured Concentration (Tmax) | 0.50 h |