Healthy
Conditions
Brief summary
The main objectives of the study are as follows: * To assess the mass balance recovery of (C-14) BI 730357-radioactivity (also expressed as 14C-BI 730357-EQ) in urine and faeces after a single oral dose of 50 mg BI 730357 base (BS) (C-14) in healthy male subjects * To provide plasma, urine, and faecal samples for metabolite profiling and structural identification
Interventions
DRUGBI 730357 mixed with [C-14]BI 730357 BS
Oral Solution
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 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 65 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 * 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. Adequate methods are: * Condoms plus use of hormonal contraception by the female partner that started at least 2 months prior to administration of trial medication (e.g. implants, injectables, combined oral or vaginal contraceptives, intrauterine device) or * Condoms plus surgical sterilization (vasectomy at least 1 year prior to enrolment) or * Condoms plus surgically sterilised partner (including hysterectomy) or * Condoms plus intrauterine device or * Condoms plus partner of non-childbearing potential (including homosexual men) Subjects are required to use condoms to prevent unintended exposure of the partner to the study drug via seminal fluid. Male and female condoms must not be used together. Alternatively, true abstinence is acceptable when it is in line with the subjec'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 (including known or suspected inflammatory bowel disease), 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 |
|---|---|---|
| Mass Balance Recovery of Total [14C]-Radioactivity in Urine (Feurine, 0-tz) | Within 18 hours (h) predose, 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 h after dosing on Day 1, continued in 24 h intervals, every 7 days from Day 21 until Day 50. | feurine, fractions of \[14C\]-radioactivity excreted in urine as percentage of the administered dose over the time interval from 0 to tz, where tz is the latest quantifiable data point across all participants. |
| Mass Balance Recovery of Total [14C]-Radioactivity in Faeces (Fefaeces, 0-tz) | Within 48 hours (h) predose, 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 and 312-336 h after dosing on Day 1 and continued in 24 h intervals, every 7 days up to Day 50. | fefaeces, 0-tz, fraction of \[14C\]-radioactivity excreted in faeces as percentage of the administered dose over the time interval from 0 to tz, where tz is the latest quantifiable data point across all participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of 14C-BI 730357-equivalent (EQ) and BI 730357 (Cmax) | Within 3:00 Hours: minutes (h:m) pre-dose, 0:30, 1:00, 1:30, 2:00, 4:00, 8:00, 12:00, 24:00, 48:00, 72:00, 120:00, 168:00, 216:00, 264:00, 312:00, 485:00, 653:00 and 821:00 after drug administration. | Cmax, maximum measured concentration of 14C-BI 730357-equivalent (EQ) and BI 730357 in plasma after a single oral dose of 50 mg BI 730357 BS (C-14) is presented. Plasma concentrations of (C-14) BI 730357-radioactivity are expressed as 14C-BI 730357-EQ. |
| Area Under the Concentration-time Curve of 14C-BI 730357-equivalent (EQ) and BI 730357 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | Within 3:00 Hours: minutes (h:m) pre-dose, 0:30, 1:00, 1:30, 2:00, 4:00, 8:00, 12:00, 24:00, 48:00, 72:00, 120:00, 168:00, 216:00, 264:00, 312:00, 485:00, 653:00 and 821:00 after drug administration. | AUC0-tz, area under the concentration-time curve of 14C-BI 730357-equivalent (EQ) and BI 730357 over the time interval from 0 to the last quantifiable time point in plasma after a single oral dose of 50 mg BI 730357 BS (C-14) is presented. Plasma concentrations of (C-14) BI 730357-radioactivity are expressed as 14C-BI 730357-EQ. |
Countries
Netherlands
Participant flow
Recruitment details
It was planned to include healthy male participants in this non-randomised, open-label, single-arm, single-dose trial. They were recruited from the volunteer's pool of the study site.
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.
Participants by arm
| Arm | Count |
|---|---|
| BI 730357 All participants were administered an oral single dose of 50 milligram (mg) BI 730357 containing \[C-14\] BI 730357 base (BS) (pure 14C-labelled hot drug substance) and BI 730357 BS (unlabelled cold drug substance). This mixture corresponds to the warm substance BI 730357 BS (C-14) containing a radioactive dose of approximately 3.7 MegaBecquerel (MBq), (100 microcurie (µCi)), and was administered in a solution of 10 milliliter (mL) volume with 240 mL of water after an overnight fast of at least 10 hours (h). | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | BI 730357 |
|---|---|
| Age, Continuous | 44.2 Years STANDARD_DEVIATION 16.6 |
| 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 | 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 | 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 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Mass Balance Recovery of Total [14C]-Radioactivity in Faeces (Fefaeces, 0-tz)
fefaeces, 0-tz, fraction of \[14C\]-radioactivity excreted in faeces as percentage of the administered dose over the time interval from 0 to tz, where tz is the latest quantifiable data point across all participants.
Time frame: Within 48 hours (h) predose, 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 and 312-336 h after dosing on Day 1 and continued in 24 h intervals, every 7 days up to Day 50.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one value for primary or secondary PK endpoints and were not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 730357 | Mass Balance Recovery of Total [14C]-Radioactivity in Faeces (Fefaeces, 0-tz) | 65.0 Percentage of administered dose (%) | Geometric Coefficient of Variation 8.09 |
Primary
Mass Balance Recovery of Total [14C]-Radioactivity in Urine (Feurine, 0-tz)
feurine, fractions of \[14C\]-radioactivity excreted in urine as percentage of the administered dose over the time interval from 0 to tz, where tz is the latest quantifiable data point across all participants.
Time frame: Within 18 hours (h) predose, 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 h after dosing on Day 1, continued in 24 h intervals, every 7 days from Day 21 until Day 50.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one value for primary or secondary PK endpoints and were not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 730357 | Mass Balance Recovery of Total [14C]-Radioactivity in Urine (Feurine, 0-tz) | 34.3 Percentage of administered dose (%) | Geometric Coefficient of Variation 19.2 |
Secondary
Area Under the Concentration-time Curve of 14C-BI 730357-equivalent (EQ) and BI 730357 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)
AUC0-tz, area under the concentration-time curve of 14C-BI 730357-equivalent (EQ) and BI 730357 over the time interval from 0 to the last quantifiable time point in plasma after a single oral dose of 50 mg BI 730357 BS (C-14) is presented. Plasma concentrations of (C-14) BI 730357-radioactivity are expressed as 14C-BI 730357-EQ.
Time frame: Within 3:00 Hours: minutes (h:m) pre-dose, 0:30, 1:00, 1:30, 2:00, 4:00, 8:00, 12:00, 24:00, 48:00, 72:00, 120:00, 168:00, 216:00, 264:00, 312:00, 485:00, 653:00 and 821:00 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one value for primary or secondary PK endpoints and were not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 730357 | Area Under the Concentration-time Curve of 14C-BI 730357-equivalent (EQ) and BI 730357 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | 14C-BI 730357-EQ | 24300 Nanomole*Hours/litre (nmol*h/L) | Geometric Coefficient of Variation 50.8 |
| BI 730357 | Area Under the Concentration-time Curve of 14C-BI 730357-equivalent (EQ) and BI 730357 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | BI 730357 | 9410 Nanomole*Hours/litre (nmol*h/L) | Geometric Coefficient of Variation 79.9 |
Secondary
Maximum Measured Concentration of 14C-BI 730357-equivalent (EQ) and BI 730357 (Cmax)
Cmax, maximum measured concentration of 14C-BI 730357-equivalent (EQ) and BI 730357 in plasma after a single oral dose of 50 mg BI 730357 BS (C-14) is presented. Plasma concentrations of (C-14) BI 730357-radioactivity are expressed as 14C-BI 730357-EQ.
Time frame: Within 3:00 Hours: minutes (h:m) pre-dose, 0:30, 1:00, 1:30, 2:00, 4:00, 8:00, 12:00, 24:00, 48:00, 72:00, 120:00, 168:00, 216:00, 264:00, 312:00, 485:00, 653:00 and 821:00 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one value for primary or secondary PK endpoints and were not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 730357 | Maximum Measured Concentration of 14C-BI 730357-equivalent (EQ) and BI 730357 (Cmax) | 14C-BI 730357-EQ | 1020 Nanomole/litre (nmol/L) | Geometric Coefficient of Variation 16.5 |
| BI 730357 | Maximum Measured Concentration of 14C-BI 730357-equivalent (EQ) and BI 730357 (Cmax) | BI 730357 | 641 Nanomole/litre (nmol/L) | Geometric Coefficient of Variation 19.2 |