Healthy
Conditions
Brief summary
To assess the influence of multiple doses of BI 425809 on single dose pharmacokinetics of midazolam (CYP3A4 probe drug), warfarin (CYP2C9 probe drug), omeprazole (CYP2C19 probe drug) and digoxin (P-gp probe drug)
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants administered first probe drugs during the reference period and BI 425809 + Probe drugs during the test period.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (blood pressure (BP), puls rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 55 years (incl.) * Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and local legislation * Ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the subject information
Exclusion criteria
* Any finding in the medical examination (including blood pressure (BP), puls rate (PR) or electrocardiogram (ECG)) is deviating from normal and judged 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 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 * Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and 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 Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 h before and up to 24h after administration of midazolam/probe drug cocktail. For detailed timeframe please see outcome measure description. | Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Short-term BI 425809 (after 3rd dose) plus midazolam": Within 3 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of midazolam on Day 3 of Treatment Period 2. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2. |
| Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description. | Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2. |
| Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description. | Area under the concentration-time curve of S-warfarin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2. |
| Area Under the Concentration-time Curve of Digoxin From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) | Blood sampling was done before and up to 95 after administration of digoxin. For detailed timeframe please see outcome measure description. | Area under the concentration-time curve of digoxin from 0 to the time of the last quantifiable data point (AUC0-tz) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 10 minutes before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 2 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 4 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 11 of Treatment Period 2. |
| Maximum Concentration of Midazolam in Plasma (Cmax) | Within 3 h before and up to 24h after administration of midazolam/probe drug cocktail. For detailed timeframe please see outcome measure description. | Maximum measured concentration of midazolam in plasma (Cmax) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Short-term BI 425809 (after 3rd dose) plus midazolam": Within 3 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of midazolam on Day 3 of Treatment Period 2. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2. |
| Maximum Concentration of Omeprazole in Plasma (Cmax) | Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description. | Maximum measured concentration of omeprazole in plasma (Cmax) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2. |
| Maximum Concentration of S-warfarin in Plasma (Cmax) | Within 3 h before and up to 24h after administration of probe drug cocktail. For detailed timeframe please see outcome measure description. | Maximum measured concentration of S-warfarin in plasma (Cmax) is presented. Arm "Treatment period 1: Probe drugs": Within 2 hours before and 0.5 hour (h), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 1 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 3 hours before and 0.5 h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24 h after administration of probe drug cocktail on Day 10 of Treatment Period 2. |
| Maximum Concentration of Digoxin in Plasma (Cmax) | Blood sampling was done before and up to 95 after administration of digoxin. For detailed timeframe please see outcome measure description. | Maximum measured concentration of digoxin in plasma (Cmax) is presented. Time frame description: Arm "Treatment period 1: Probe drugs": Within 10 minutes before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 2 of Treatment Period 1. Arm "Treatment period 2: Steady state BI 425809 plus probe drugs": Within 4 hours before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 47h, 71h, 95h after digoxin administration on Day 11 of Treatment Period 2. |
Countries
Germany
Contacts
STUDY_CHAIRBoehringer Ingelheim
Boehringer Ingelheim
Participant flow
Recruitment details
This trial in healthy male subjects applied an open-label, crossover design consisting of 2 treatment periods with a fixed sequence. It assessed the influence of multiple doses of BI 425809 (14 days) on single dose pharmacokinetics (PK) of midazolam, warfarin, omeprazole, and digoxin. Furthermore, the short-term effect of BI 425809 on single dose midazolam PK was investigated.
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 | 37.1 Years STANDARD_DEVIATION 13.1 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| other Total, other adverse events | 4 / 13 | 11 / 12 | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 13 |
Outcome results
None listed