Healthy
Conditions
Brief summary
To investigate the safety and tolerability of BI 416970 and to assess the pharmacokinetics (PK) of single rising doses of BI 416970. A further objective is to assess the influence of CYP2C9 phenotype on the PK of BI 416970.
Interventions
DRUGPlacebo to BI 416970
single rising doses
DRUGBI 416970
single rising doses
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead electrocardiogram, and clinical laboratory * Age 18 to 50 years (incl.) * Body Mass Index 18.5 to 29.9 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation * Known genotype of CYP2C9 isoenzyme
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure, Pulse Rate or Electrocardiogram) is deviating from normal and judged as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside of ranges 90-140 mmHg, diastolic blood pressure outside of ranges 50-90 mmHg, or pulse rate outside the range of 50 to 90 bpm * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease judged as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication * Diseases of the central nervous system (such as epilepsy), other peripheral neurological disorders or psychiatric disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug-related Adverse Events | AEs were recorded throughout the trial | Percentage of subjects with drug-related adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 2 hour (h) before drug administration and 15minutes (min), 30min, 45min, 1h,1h 30min, 1h 45min, 2h, 3h, 4h, 4h 15min, 6h, 7h, 8h, 10h, 12h, 24h, 34h and 48h after drug administration | Cmax (maximum measured concentration of the analyte in plasma) |
| AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 2 hour (h) before drug administration and 15minutes (min), 30min, 45min, 1h,1h 30min, 1h 45min, 2h, 3h, 4h, 4h 15min, 6h, 7h, 8h, 10h, 12h, 24h, 34h and 48h after drug administration | AUC 0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |
Countries
Germany
Participant flow
Recruitment details
The study was conducted in eight groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo The medication was administered as a single oral dose (Dose = NA) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 15 |
| BI 416970 10mg The medication was administered as a single oral dose (dose = 10 mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 6 |
| BI 416970 25mg The medication was administered as a single oral dose (Dose = 25mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 10 |
| BI 416970 50mg The medication was administered as a single oral dose (dose = 50mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 6 |
| BI 416970 100mg The medication was administered as a single oral dose (Dose = 100mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 6 |
| BI 416970 200mg The medication was administered as a single oral dose (Dose = 200mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 6 |
| BI 416970 400mg The medication was administered as a single oral dose (Dose = 400mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 5 |
| BI 416970 600mg The medication was administered as a single oral dose (Dose = 600mg) with a total of about 240 mL water in the standing or sitting position following an overnight fast of at least 10 h. | 6 |
| Total | 60 |
Baseline characteristics
| Characteristic | Placebo | BI 416970 10mg | BI 416970 25mg | BI 416970 50mg | BI 416970 100mg | BI 416970 200mg | BI 416970 400mg | BI 416970 600mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 9.2 | 35.7 years STANDARD_DEVIATION 7.9 | 38.9 years STANDARD_DEVIATION 8.7 | 34.2 years STANDARD_DEVIATION 10 | 31.0 years STANDARD_DEVIATION 4.6 | 31.2 years STANDARD_DEVIATION 12.7 | 34.0 years STANDARD_DEVIATION 9.5 | 35.3 years STANDARD_DEVIATION 10.9 | 34.5 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 60 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 15 | 1 / 6 | 3 / 10 | 1 / 6 | 0 / 6 | 2 / 6 | 2 / 5 | 1 / 6 | 10 / 45 | 11 / 60 |
| serious Total, serious adverse events | 0 / 15 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 45 | 0 / 60 |
Outcome results
Primary
Percentage of Subjects With Drug-related Adverse Events
Percentage of subjects with drug-related adverse events
Time frame: AEs were recorded throughout the trial
Population: The PKS included 59 subjects of the TS who provided at least 1 value of the endpoints Cmax, AUC0-∞, or AUC0-tz.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug-related Adverse Events | 6.7 percentage of participants |
| BI 416970 10mg | Percentage of Subjects With Drug-related Adverse Events | 0.0 percentage of participants |
| BI 416970 25mg | Percentage of Subjects With Drug-related Adverse Events | 0.0 percentage of participants |
| BI 416970 50mg | Percentage of Subjects With Drug-related Adverse Events | 0.0 percentage of participants |
| BI 416970 100mg | Percentage of Subjects With Drug-related Adverse Events | 0.0 percentage of participants |
| BI 416970 200mg | Percentage of Subjects With Drug-related Adverse Events | 0.0 percentage of participants |
| BI 416970 400mg | Percentage of Subjects With Drug-related Adverse Events | 20.0 percentage of participants |
| BI 416970 600mg | Percentage of Subjects With Drug-related Adverse Events | 0.0 percentage of participants |
Secondary
AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
AUC 0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time frame: 2 hour (h) before drug administration and 15minutes (min), 30min, 45min, 1h,1h 30min, 1h 45min, 2h, 3h, 4h, 4h 15min, 6h, 7h, 8h, 10h, 12h, 24h, 34h and 48h after drug administration
Population: The PKS included 59 subjects of the TS who provided at least 1 value of the endpoints Cmax, AUC0-∞, or AUC0-tz.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 72.8 nmol*h/L | Geometric Coefficient of Variation 41.5 |
| BI 416970 10mg | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 195 nmol*h/L | Geometric Coefficient of Variation 49.8 |
| BI 416970 25mg | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 566 nmol*h/L | Geometric Coefficient of Variation 54 |
| BI 416970 50mg | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 992 nmol*h/L | Geometric Coefficient of Variation 36.1 |
| BI 416970 100mg | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 1770 nmol*h/L | Geometric Coefficient of Variation 34.6 |
| BI 416970 200mg | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 3970 nmol*h/L | Geometric Coefficient of Variation 61.3 |
| BI 416970 400mg | AUC 0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | 6150 nmol*h/L | Geometric Coefficient of Variation 23.2 |
Comparison: A power model was used to describe functional relationship between dose and Pk parameters. For the evaluation of dose proportionality,slope parameter (B), a two-sided 90% confidence interval of the slope was calculated. Perfect dose proportionality would correspond to a slope of 1.90% CI: [0.9946, 1.1518]
Comparison: A power model was used to describe functional relationship between dose and Pk parameters. For the evaluation of dose proportionality,slope parameter (B), a two-sided 90% confidence interval of the slope was calculated. Perfect dose proportionality would correspond to a slope of 1.90% CI: [0.8174, 1.1032]
Secondary
Cmax (Maximum Measured Concentration of the Analyte in Plasma)
Cmax (maximum measured concentration of the analyte in plasma)
Time frame: 2 hour (h) before drug administration and 15minutes (min), 30min, 45min, 1h,1h 30min, 1h 45min, 2h, 3h, 4h, 4h 15min, 6h, 7h, 8h, 10h, 12h, 24h, 34h and 48h after drug administration
Population: The PKS included 59 subjects of the TS who provided at least 1 value of the endpoints Cmax, AUC0-∞, or AUC0-tz.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 15.2 nmol/L | Geometric Coefficient of Variation 66.3 |
| BI 416970 10mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 44.0 nmol/L | Geometric Coefficient of Variation 80.5 |
| BI 416970 25mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 154 nmol/L | Geometric Coefficient of Variation 69.6 |
| BI 416970 50mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 250 nmol/L | Geometric Coefficient of Variation 37.2 |
| BI 416970 100mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 482 nmol/L | Geometric Coefficient of Variation 40.3 |
| BI 416970 200mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 1060 nmol/L | Geometric Coefficient of Variation 70.4 |
| BI 416970 400mg | Cmax (Maximum Measured Concentration of the Analyte in Plasma) | 1610 nmol/L | Geometric Coefficient of Variation 50.2 |
Comparison: A power model was used to describe functional relationship between dose and Pk parameters. For the evaluation of dose proportionality,slope parameter (B), a two-sided 90% confidence interval of the slope was calculated. Perfect dose proportionality would correspond to a slope of 1.90% CI: [1.0249, 1.2376]
Comparison: A power model was used to describe functional relationship between dose and Pk parameters. For the evaluation of dose proportionality,slope parameter (B), a two-sided 90% confidence interval of the slope was calculated. Perfect dose proportionality would correspond to a slope of 1.90% CI: [0.783, 1.1307]