Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of BI 425809 given alone (Reference) compared to a combined administration with the moderate CYP3A4 inducer bosentan (Test) following repeated oral administration.
Interventions
DRUGBI 425809
One daily film-coated tablet of 10 mg with 240 mL of water for 10 days (R) and for 14 days (T).
DRUGBosentan
Two daily film-coated tablets of 125 mg with 240 mL of water for 14 days (T).
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients cross over from reference treatment (R) to test treatment (T) (two periods, fixed sequence).
Eligibility
Sex/Gender
MALE
Age
30 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests * Age of 30 to 55 years (inclusive) * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 millimetre of mercury (mmHg), or pulse rate outside the range of 45 to 90 beats per minute (bpm) * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease assessed as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair) * Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders * History of relevant orthostatic hypotension, fainting spells, or blackouts * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 425809 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | Period 1: within 2 h before and 240 h after BI 425809 administration on Day 1 (for details, see description). Period 2: within 142 h and 335 h after BI 425809 and bosentan administration on Day 1 (for details, see description). | Area under the concentration-time curve of BI 425809 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) is reported. The dosing interval τ is 24 hours (h). Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model. The ANOVA model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subjects' was considered as random, whereas 'treatment' was considered as fixed. Time frame period 1: within 2 h before and 192 h, 216 h, 216.5 h, 217 h, 217.5 h, 218 h, 218.5 h, 219 h, 219.5 h, 220 h, 220.5 h, 222 h, 224 h, 226 h, 228 h, 240 h after BI 425809 administration on Day 1. Time frame period 2: 142 h, 311 h, 311.5 h, 312 h, 312.5 h, 313 h, 313.5 h, 314 h, 314.5 h, 315 h, 315.5 h, 317 h, 319 h, 321 h, 323 h, 335 h after BI 425809 and bosentan administration on Day 1. |
| Maximum Measured Concentration of BI 425809 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | Period 1: within 2 h before and 240 h after BI 425809 administration on Day 1 (for details, see description). Period 2: within 142 h and 335 h after BI 425809 and bosentan administration on Day 1 (for details, see description). | Maximum measured concentration of BI 425809 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) is reported. The dosing interval τ is 24 hours (h). Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model. The ANOVA model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subjects' was considered as random, whereas 'treatment' was considered as fixed. Time frame period 1: within 2 h before and 192 h, 216 h, 216.5 h, 217 h, 217.5 h, 218 h, 218.5 h, 219 h, 219.5 h, 220 h, 220.5 h, 222 h, 224 h, 226 h, 228 h, 240 h after BI 425809 administration on Day 1. Time frame period 2: 142 h, 311 h, 311.5 h, 312 h, 312.5 h, 313 h, 313.5 h, 314 h, 314.5 h, 315 h, 315.5 h, 317 h, 319 h, 321 h, 323 h, 335 h after BI 425809 and bosentan administration on Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Concentration of BI 425809 in Plasma at Steady State Within a Uniform Dosing Interval τ (Cmin,ss) | Period 1: within 2 h before and 240 h after BI 425809 administration on Day 1 (for details, see description). Period 2: within 142 h and 335 h after BI 425809 and bosentan administration on Day 1 (for details, see description). | Minimum concentration of BI 425809 in plasma at steady state within a uniform dosing interval τ (Cmin,ss) is reported. The dosing interval τ is 24 hours (h). Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model. The ANOVA model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subjects' was considered as random, whereas 'treatment' was considered as fixed. Time frame period 1: within 2 h before and 192 h, 216 h, 216.5 h, 217 h, 217.5 h, 218 h, 218.5 h, 219 h, 219.5 h, 220 h, 220.5 h, 222 h, 224 h, 226 h, 228 h, 240 h after BI 425809 administration on Day 1. Time frame period 2: 142 h, 311 h, 311.5 h, 312 h, 312.5 h, 313 h, 313.5 h, 314 h, 314.5 h, 315 h, 315.5 h, 317 h, 319 h, 321 h, 323 h, 335 h after BI 425809 and bosentan administration on Day 1. |
Countries
Germany
Participant flow
Recruitment details
This was a non-randomised, open-label, two-period fixed sequence trial in healthy male subjects in order to compare the test treatment (T, BI 425809 given in combination with bosentan) to the reference treatment (R, BI 425809 given alone).
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.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 3 / 14 | 7 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 |
Outcome results
None listed