Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the relative bioavailability of a single dose of BI 425809 when given alone (Reference, B) compared with co-administration (Test, A) on the 7th day of a 10-day treatment with rifampicin following oral administration in healthy male volunteers.
Interventions
DRUGRifampicin
once daily
DRUGBI 425809
once daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the assessment of the investigator, 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 18 to 55 years (incl.) * 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
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure (BP), Pulse 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 * History of relevant orthostatic hypotension, fainting spells, or blackouts * Chronic or relevant acute infections * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation) * Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) * Inability to refrain from smoking on specified trial days * Alcohol abuse (consumption of more than 20 g per day) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial * Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial * Inability to comply with dietary regimen of trial site * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From 0 to 168 Hours Time Point of BI 425809 (AUC0-168). | Pharmacokinetic samples were collected at 2:00 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 168:00 hours post dose. | This endpoint calculates area under the concentration-time curve of BI 425809 in plasma over the time interval from 0 to 168 hour time point. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale including subject as random effect and treatment as fixed effect. |
| Maximum Concentration of BI 425809 in Plasma (Cmax). | Pharmacokinetic samples were collected at 2:00 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 168:00 hours post dose. | This outcome is maximum measured concentration of the BI 425809 in plasma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 425809 in Plasma With and Without Co-administration of Rifampicin Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞). | Pharmacokinetic samples were collected at 2:00 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30, 4:00, 4:30, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 168:00 hours post dose. | This endpoint calculates area under the concentration-time curve of BI 425809 in plasma with and without adminstration of Rifampicin over the time interval from 0 extrapolated to infinity. |
| Terminal Half-life of the Metabolite BI 761036 in Plasma (t1/2) | Pharmacokinetic samples were collected at 2:00 hour Pre-dose and at 3:00, 6:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00, 168:00, 216:00, 264:00, 336:00, 408:00, 504:00, 576:00, 672:00, 744:00, 840:00 and 1008:00 hours post dose. | Half life is the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. |
Countries
Germany
Participant flow
Recruitment details
This is an open-label, two-period, fixed sequence trial in healthy subjects. A total of 16 subjects were entered and completed the trial. The subjects were treated with 1 tablet of 25 milligram (mg) BI 425809 in period 1 and with multiple doses of Rifampicin (Eremfat®) 600 mg and single dose of 25 mg BI 425809 in period 2.
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 | 38.1 Years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 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 | 0 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 | 16 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 16 | 16 / 16 | 3 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
None listed