Healthy
Conditions
Brief summary
To investigate the absolute oral bioavailability of BI 730357 administered as tablet compared with \[C-14\]BI 730357 BS administered as intravenous microtracer
Interventions
DRUGBI 730357
Oral dose
DRUGBI 730357 mixed with [C-14] BI 730357 BS
Intravenous dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
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, 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) * Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation * Further inclusion criteria apply
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed 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 assessed 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 * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 730357 Over the Time Interval From 0 to Infinity (Dose Normalized). | Test treatment T: within 3h before and 1,1.5,2,2.5,3.5,5,7,12,24,72,120,168h after oral administration. Reference treatment R: within 3h before and 5,10,15,30,45 minutes and 1.25,2.25,3.75,5.75,10.75,22.75,70.75,118.75,166.75h after start of iv infusion. | Area under the concentration-time curve of the analyte over the time interval from 0 to infinity (AUC0-∞). For both arms results are presented in millimole (mmol) \* hours (h) / Litre (L) / kilogram (kg). This was achieved by transforming the reference arm to the treatment arm and normalizing the results according to the respective dose. |
Countries
Netherlands
Participant flow
Recruitment details
The trial was performed as a non-randomised, open-label, single arm, single period trial design in healthy male subjects in order to investigate the absolute oral bioavailability compared to the intravenous administered reference treatment of BI 730357.
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 |
|---|---|
| All Subjects 1 tablet with 50 milligram (mg) BI 730357 was administered as a single oral dose with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) as test treatment (T) followed by 100 microgram (μg) of BI 730357 base (BS) (C-14) (2 μg radiolabelled \[C-14\]BI 730357 BS mixed with 98 μg unlabeled BI 730357) administered as 15 minutes (min) intravenous (i.v.) infusion as reference treatment (R) starting 1.25 hours (h) after oral administration. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 45.2 Years STANDARD_DEVIATION 14.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 4 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 | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 730357 Over the Time Interval From 0 to Infinity (Dose Normalized).
Area under the concentration-time curve of the analyte over the time interval from 0 to infinity (AUC0-∞). For both arms results are presented in millimole (mmol) \* hours (h) / Litre (L) / kilogram (kg). This was achieved by transforming the reference arm to the treatment arm and normalizing the results according to the respective dose.
Time frame: Test treatment T: within 3h before and 1,1.5,2,2.5,3.5,5,7,12,24,72,120,168h after oral administration. Reference treatment R: within 3h before and 5,10,15,30,45 minutes and 1.25,2.25,3.75,5.75,10.75,22.75,70.75,118.75,166.75h after start of iv infusion.
Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetic (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 730357 50mg Tablet (T) | Area Under the Concentration-time Curve of BI 730357 Over the Time Interval From 0 to Infinity (Dose Normalized). | NA mmol*h/L/kg |
| BI 730357 BS (C-14) 100 µg Infusion (R) | Area Under the Concentration-time Curve of BI 730357 Over the Time Interval From 0 to Infinity (Dose Normalized). | NA mmol*h/L/kg |
90% CI: [56.69, 87.23]