Healthy
Conditions
Brief summary
This trial intends to investigate the basic pharmacokinetics of BI 425809 and \[14C\]- radioactivity, including mass balance, excretion pathways and metabolism following a single oral dose of 25 mg BI 425809 (C-14) given to healthy male subjects
Interventions
DRUGBI 425809 mixed with [C-14] BI425809
Single oral dose of 25 milligram (mg) mixture of Carbon 14 labelled \[14C\] BI 425809 XX, containing a radioactive dose of 3.7 MegaBecquerel (MBq), and unlabeled BI 425809 XX dissolved in 12.5 milliliter (mL) polyethylene glycol 400 (PEG) as solvent.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests * Age of 18 to 65 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 GCP and local legislation * Subjects who are sexually active must use, with their partner, highly effective contraception from the time of administration of trial medication until 4 months after administration of trial medication. * Subjects are required to use condoms to prevent unintended exposure of the partner to the study drug via seminal fluid. Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, with their partner, they must comply with the contraceptive requirements detailed above.
Exclusion criteria
* Any finding in the medical examination (including BP, PR or 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 139 mmHg, diastolic blood pressure outside the range of 45 to 89 mmHg, or pulse rate outside the range of 40 to 100 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 * Clinically significant gastrointestinal, hepatic, renal, respiratory (including but not limited to interstitial lung disease), 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). Use of CYP3A4 inhibitors and inducers 1 week prior to administration of trial medication * 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 5 cigarettes or 1 cigars or 1 pipes per day) * Inability to refrain from smoking on trial days * Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 ml of spirits) * 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 4 days prior to administration of trial medication or during the trial * Inability to comply with dietary regimen of trial site * A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening * A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mass Balance Recovery of Total [14C]-Radioactivity in Urine (Feurine, 0-t2) | PKurine samples were collected within 2 hours predose and within 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336, 485-509 and 653-677 hours after dosing on Day 1. | feurine, 0-t2, fraction of \[14C\]-radioactivity excreted in urine as percentage of the administered dose over the time interval from 0 to t2, where t2 is the last quantifiable data point across all participants mass balance recovery of total \[14C\]-radioactivity in urine. |
| Mass Balance Recovery of Total [14C]-Radioactivity in Faeces (Fefaeces, 0-t2) | PKfaeces samples were collected within 2 hours predose and within 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336, 485-509 and 653-677 hours after dosing on Day 1. | fefaeces, 0-t2, fraction of \[14C\]-radioactivity excreted in faeces as percentage of the administered dose over the time interval from 0 to t2, where t2 is the last quantifiable data point across all participants mass balance recovery of total \[14C\]-radioactivity in faeces. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of the [14C]-Radioactivity and BI 425809 (Cmax) | PK samples were collected at 2 hours prior to drug administration and at 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 485, 653 hours after drug administration. | Maximum measured concentration of the \[14C\]-radioactivity and BI 425809 (Cmax). |
| Area Under the Concentration-time Curve of the [14C]-Radioactivity and BI 425809 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | PK samples were collected at 2 hours prior to drug administration and at 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 485, 653 hours after drug administration. | Area under the concentration-time curve of the \[14C\]-radioactivity and BI 425809 over the time interval from 0 to the last quantifiable time point (AUC0-tz). For \[14C\]-radioactivity the latest tz was 653 h whereas for BI 425809 the latest tz was 336 h. |
Countries
Netherlands
Participant flow
Recruitment details
This trial was performed as a non-randomised, open-label, single period, single arm trial in healthy male participants.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensure that they (all participants) met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 45.7 Years STANDARD_DEVIATION 17.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 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 | 1 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 | 5 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
None listed