Healthy
Conditions
Brief summary
This trial is intended to examine the absolute oral bioavailability of BI 1015550 as tablet formulation for oral administration, using an intravenous microtracer approach with \[14C\]-labelled BI 1015550. These data are considered necessary to further support the understanding of the pharmacokinetics of BI 1015550.
Interventions
DRUGBI 1015550
Treatment T
DRUGBI 1015550 mixed with [C-14]-BI 1015550
Treatment R
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, 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 in accordance with International Council for Harmonisation-Good Clinical Practice (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 millimetre(s) of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 40 to 100 beats per minute (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 (including but not limited to major depressive disorder or history of suicide attempts) * History of relevant orthostatic hypotension, fainting spells, or blackouts Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Between waking up and still prior to drug intake and 0.5*, 0.75*, 1*, 1.5*, 1.58±, 1.67±, 1.75, 2, 2.5±, 3, 4, 5±, 6, 7±, 8, 12, 16, 24, 36, 48, 72, 120, 168, 216± hours after intake of oral BI 1015550 tablet, *for T treatment, ±only for R treatment. | Dose normalized AUC0-inf of \[14C\]-BI 1015550 after intravenous (i.v.) administration and AUC0-inf of BI 1015550 after oral (p.o.) administration are reported. The analysis was performed only on the pharmacologically active R-enantiomer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | Between waking up and still prior to drug intake and 0.5*, 0.75*, 1*, 1.5*, 1.58±, 1.67±, 1.75, 2, 2.5±, 3, 4, 5±, 6, 7±, 8, 12, 16, 24, 36, 48, 72, 120, 168, 216± hours after intake of oral BI 1015550 tablet, *for T treatment, ±only for R treatment. | Dose normalized Cmax of BI 1015550 after oral administration and Cmax of \[14C\]-BI 1015550 after intravenous administration is reported. The analysis was performed only on the pharmacologically active R-enantiomer. |
Countries
Netherlands
Participant flow
Recruitment details
A non-randomised, open-label, single period, single arm trial to determine the absolute oral bioavailability of BI 1015550 in healthy male subjects.
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 |
|---|---|
| 18 mg BI 1015550 / 100 μg BI 1015550 (C-14) One film-coated tablet of 18 milligram (mg) BI 1015550 was administered as single oral dose with 240 milliliter of water after an overnight fast of at least 10 hours on Day 1 as test treatment (T). 100 microgram (μg) BI 1015550 (C-14) solution (consisting of 90 μg unlabelled BI 1015550 mixed with 10 μg labelled \[14C\]-BI 1015550 in 10 mL intravenous solution with a final concentration of 10 μg BI 1015550 (C-14)/mL) was administered as single intravenous infusion over 15 minutes on Day 1 as reference treatment (R). The radioactive dose per infusion was \
40 kilobecquerel (kBq). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | 18 mg BI 1015550 / 100 μg BI 1015550 (C-14) |
|---|---|
| Age, Continuous | 28.9 Years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 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 | 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 | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Dose Normalized Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Dose normalized AUC0-inf of \[14C\]-BI 1015550 after intravenous (i.v.) administration and AUC0-inf of BI 1015550 after oral (p.o.) administration are reported. The analysis was performed only on the pharmacologically active R-enantiomer.
Time frame: Between waking up and still prior to drug intake and 0.5*, 0.75*, 1*, 1.5*, 1.58±, 1.67±, 1.75, 2, 2.5±, 3, 4, 5±, 6, 7±, 8, 12, 16, 24, 36, 48, 72, 120, 168, 216± hours after intake of oral BI 1015550 tablet, *for T treatment, ±only for R treatment.
Population: Pharmacokinetic (PK) set (PKS): All subjects in the treated set (TS) who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| R-BI 1015550 18 mg tablet (T) | Dose Normalized Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 118.27 Hours*millimole/liter/kilogram | Standard Error 1.07 |
| 14C-R-BI 1015550 10 μg i.v. (R) | Dose Normalized Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 161.69 Hours*millimole/liter/kilogram | Standard Error 1.07 |
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model and then then back-transformed to the original scale to provide the point estimate and 90% confidence interval. The model included effects accounting for the following sources of variation: 'subjects' and 'formulation'. The effect 'subjects' was considered as random, whereas the 'formulation' effect was considered as fixed.90% CI: [67.32, 79.48]
Secondary
Dose Normalized Maximum Measured Concentration of BI 1015550 in Plasma (Cmax)
Dose normalized Cmax of BI 1015550 after oral administration and Cmax of \[14C\]-BI 1015550 after intravenous administration is reported. The analysis was performed only on the pharmacologically active R-enantiomer.
Time frame: Between waking up and still prior to drug intake and 0.5*, 0.75*, 1*, 1.5*, 1.58±, 1.67±, 1.75, 2, 2.5±, 3, 4, 5±, 6, 7±, 8, 12, 16, 24, 36, 48, 72, 120, 168, 216± hours after intake of oral BI 1015550 tablet, *for T treatment, ±only for R treatment.
Population: Pharmacokinetic (PK) set (PKS): All subjects in the treated set (TS) who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| R-BI 1015550 18 mg tablet (T) | Dose Normalized Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 24.53 Picomole/Liter/microgram | Geometric Coefficient of Variation 1.13 |
| 14C-R-BI 1015550 10 μg i.v. (R) | Dose Normalized Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 73.05 Picomole/Liter/microgram | Geometric Coefficient of Variation 1.13 |
Comparison: Analysis of variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints were logtransformed (natural logarithm) prior to fitting the ANOVA model and then then back-transformed to the original scale to provide the point estimate and 90% confidence interval. The model included effects accounting for the following sources of variation: 'subjects' and 'formulation'. The effect 'subjects' was considered as random, whereas the 'formulation' effect was considered as fixed.90% CI: [29.4, 38.36]