Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the basic pharmacokinetics of BI 764198 and its metabolites, total radioactivity including mass balance, excretion pathways and metabolism following oral administration to healthy male volunteers of a single oral dose of BI 764198 (C-14) in i) a classical hADME approach and ii) a hADME microtracer approach.
Interventions
DRUGBI 764198 (C-14) (approach 1)
BI 764198 (C-14) (approach 1)
DRUGBI 764198 (C-14) (approach 2)
BI 764198 (C-14) (approach 2)
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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, 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 18 to 65 years (inclusive) * BMI of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent in accordance with 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 45 to 90 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 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 Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mass Balance Recovery of Total Radioactivity in Urine and Faeces: Amount Excreted Within the Time Interval From 0 to the Time of the Last Quantifiable Data Point as a Percentage of the Administered Dose (fe0-tz) for Urine and Faeces. | Urine and feces sample collection: 48 hours before and up to 725 hours after drug administration. The details are mentioned in the description section. | Urine: Within 2 hours before drug administration, and at 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours post-drug administration. Feces: up to 48 hours (feces) before drug administration, and at 24, 48, 72, 96, 120, 144, 168, and 192 hours post-drug administration. If warranted, further 24-hour collections at trial site were performed at 365-389, 533-557-, and 701-725-hours post-administration depending on participants fulfilling the radioactivity recovery criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-tz, Area Under the Concentration-time Curve of [14C]-BI 764198-EQ Over the Time Interval From 0 to the Last Quantifiable Time Point in Plasma After Single Oral Administration of [14C]BI 764198. | Within 3 hours before drug intake, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 365, 533, and 701 hours post-administration. | For participants in the cohorts 1 and 2a, further samples were collected at 365, 533, and 701 hours only if \[14C\]-radioactivity in plasma post 216 hours after drug administration exceeded the quantification limit at two consecutive points. The measurements of \[14C\]-BI 764198-EQ concentration is adjusted or standardized to reflect a "bioequivalent" form. |
| AUC0-tz, Area Under the Concentration-time Curve of BI 764198 Over the Time Interval From 0 to the Last Quantifiable Time Point in Plasma After Single Oral Administration of [14C]BI 764198. | Within 3 hours before drug intake, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 365, 533, and 701 hours post-administration. | For participants in the cohorts 1 and 2a, further samples were collected at 365, 533, and 701 hours only if \[14C\]-radioactivity in plasma post 216 hours after drug administration exceeded the quantification limit at two consecutive points. |
| Cmax, Maximum Measured Concentration of [14C]-BI 764198-EQ in Plasma After Single Oral Administration of [14C]BI 76418. | Within 3 hours before drug intake, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 365, 533, and 701 hours post-administration. | For participants in the cohorts 1 and 2a, further samples were collected at 365, 533, and 701 hours only if \[14C\]-radioactivity in plasma post 216 hours after drug administration exceeded the quantification limit at two consecutive points. The measurements of \[14C\]-BI 764198-EQ concentration is adjusted or standardized to reflect a "bioequivalent" form. This standardization ensures that the data can be accurately compared to the unlabeled BI 764198. |
| Cmax, Maximum Measured Concentration of BI 76418 in Plasma After Single Oral Administration of [14C]BI 76418. | Within 3 hours before drug intake, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 365, 533, and 701 hours post-administration. | For participants in the cohorts 1 and 2a, further samples were collected at 365, 533, and 701 hours only if \[14C\]-radioactivity in plasma post 216 hours after drug administration exceeded the quantification limit at two consecutive points. |
Countries
Netherlands
Participant flow
Recruitment details
This open-label, non randomised, single-dose, single-period, two-arm phase I trial investigates the mass balance, metabolism, and pharmacokinetics of a single dose of BI 764198 in healthy males. Study arm 1 uses a classical hADME approach, while study arm 2 uses a microtracer approach and is divided into two cohorts (2a and 2b). Participants were allocated in a 1:2 ratio based on availability.
Pre-assignment details
An additional cohort (2b) was introduced due to errors in plasma samples from the first 8 participants in cohort 2a, preventing reliable metabolite profiling. Cohort 2b received the same treatment to enable proper profiling. The assessment schedule for cohort 2b was abbreviated, release criteria were not applied, and data from cohorts 2a and 2b were pooled for analysis. The sample size for the microtracer approach was doubled compared to the classical ADME approach.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 31.6 years STANDARD_DEVIATION 11.5 |
| 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 | 24 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 3 / 8 | 5 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
None listed