Healthy
Conditions
Brief summary
A study in healthy man to investigate the absolute bioavailability of 100mg BI 765080, once administered as subcutaneous (SC) injection and once administered as intravenous infusion.
Interventions
DRUGBI 765080
BI 765080
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Caucasian male subjects according to the assessment of the investigator, as based on a complete medical history, a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12- lead Electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 55 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
Exclusion criteria
* Any finding in the medical examination (including 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 of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 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 * 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 Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 765080 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours (h) before and 0.5h, 2h, 4h, 8h, 12h, 24h, 34h, 48h, 72h, 96h*, 120h, 168h, 240h, 312h, 480h, 648h and 1320h after administration of BI 765080. * Applicable only for the arm 100 mg BI 765080 SC injection (T) | Area under the concentration-time curve of BI 765080 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. |
| Maximum Measured Concentration of BI 765080 in Plasma (Cmax) | Within 3 hours (h) before and 0.5h, 2h, 4h, 8h, 12h, 24h, 34h, 48h, 72h, 96h*, 120h, 168h, 240h, 312h, 480h, 648h and 1320h after administration of BI 765080. * Applicable only for the arm 100 mg BI 765080 SC injection (T). | Maximum measured concentration of BI 765080 in plasma (Cmax) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) before and 0.5h, 2h, 4h, 8h, 12h, 24h, 34h, 48h, 72h, 96h*, 120h, 168h, 240h, 312h, 480h, 648h and 1320h after administration of BI 765080. * Applicable only for the arm 100 mg BI 765080 SC injection (T). | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. |
| Occurrence of Drug-related Adverse Events | From start of drug of administration until end of trial, up to 59 days. | Percentage of participants with drug-related adverse events is reported. |
Countries
Belgium
Participant flow
Recruitment details
The trial was randomized, open-label, and single-dose, with matched parallel groups (test treatment (T) group: subcutaneous (SC) injection of 100 milligram (mg) BI 765080; reference treatment (R) group: intravenous (IV) infusion of 100 mg BI 765080). Subjects in the T and R groups were matched based on age and body weight.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trail. Subjects attend 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 |
|---|---|
| 100 mg BI 765080 SC Injection (T) Participants were administered a single dose of 100 milligram (mg) of BI 765080 as subcutaneous injection (SC). | 14 |
| 100 mg BI 765080 IV Infusion (R) Participants were administered a single dose of 100 milligram (mg) of BI 765080 as intravenous infusion (IV). | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | 100 mg BI 765080 SC Injection (T) | Total | 100 mg BI 765080 IV Infusion (R) |
|---|---|---|---|
| Age, Continuous | 40.4 Years STANDARD_DEVIATION 12.2 | 40.8 Years STANDARD_DEVIATION 11.1 | 41.1 Years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 28 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 28 Participants | 14 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 28 Participants | 14 Participants |
| Weight | 81.91 kilogram (kg) STANDARD_DEVIATION 9.72 | 82.41 kilogram (kg) STANDARD_DEVIATION 9.21 | 82.92 kilogram (kg) STANDARD_DEVIATION 9.01 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 8 / 14 | 2 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 765080 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 765080 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Time frame: Within 3 hours (h) before and 0.5h, 2h, 4h, 8h, 12h, 24h, 34h, 48h, 72h, 96h*, 120h, 168h, 240h, 312h, 480h, 648h and 1320h after administration of BI 765080. * Applicable only for the arm 100 mg BI 765080 SC injection (T)
Population: The pharmacokinetic (PK) parameter analysis set (PKS): Including all subjects in the treated set (TS) who provided non-excluded data for at least one primary or secondary PK endpoint. Descriptive and model-based analyses of PK parameters were based on the PKS.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 100 mg BI 765080 SC Injection (T) | Area Under the Concentration-time Curve of BI 765080 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 3528304.5 hours*nanogram/milliliter |
| 100 mg BI 765080 IV Infusion (R) | Area Under the Concentration-time Curve of BI 765080 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 7625263.8 hours*nanogram/milliliter |
Comparison: The statistical model used for the analysis of this primary endpoint was an analysis of variance (ANOVA). The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included a fixed effect for treatment assignment and a random effect for matching pair (each matched pair in the study was assigned a number for the analysis).90% CI: [38.3, 55.9]
Primary
Maximum Measured Concentration of BI 765080 in Plasma (Cmax)
Maximum measured concentration of BI 765080 in plasma (Cmax) is reported.
Time frame: Within 3 hours (h) before and 0.5h, 2h, 4h, 8h, 12h, 24h, 34h, 48h, 72h, 96h*, 120h, 168h, 240h, 312h, 480h, 648h and 1320h after administration of BI 765080. * Applicable only for the arm 100 mg BI 765080 SC injection (T).
Population: The pharmacokinetic (PK) parameter analysis set (PKS): Including all subjects in the treated set (TS) who provided non-excluded data for at least one primary or secondary PK endpoint. Descriptive and model-based analyses of PK parameters were based on the PKS.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 100 mg BI 765080 SC Injection (T) | Maximum Measured Concentration of BI 765080 in Plasma (Cmax) | 9582.0 nanogram/milliliter |
| 100 mg BI 765080 IV Infusion (R) | Maximum Measured Concentration of BI 765080 in Plasma (Cmax) | 35718.4 nanogram/milliliter |
Comparison: The statistical model used for the analysis of this primary endpoint was an analysis of variance (ANOVA). The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included a fixed effect for treatment assignment and a random effect for matching pair (each matched pair in the study was assigned a number for the analysis).90% CI: [23.2, 31.1]
Secondary
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Time frame: Within 3 hours (h) before and 0.5h, 2h, 4h, 8h, 12h, 24h, 34h, 48h, 72h, 96h*, 120h, 168h, 240h, 312h, 480h, 648h and 1320h after administration of BI 765080. * Applicable only for the arm 100 mg BI 765080 SC injection (T).
Population: The pharmacokinetic (PK) parameter analysis set (PKS): Including all subjects in the treated set (TS) who provided non-excluded data for at least one primary or secondary PK endpoint. Descriptive and model-based analyses of PK parameters were based on the PKS.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 100 mg BI 765080 SC Injection (T) | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3590175.4 hours*nanogram/milliliter |
| 100 mg BI 765080 IV Infusion (R) | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 7638615.9 hours*nanogram/milliliter |
Comparison: The statistical model used for the analysis of this secondary endpoint was an analysis of variance (ANOVA). The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included a fixed effect for treatment assignment and a random effect for matching pair (each matched pair in the study was assigned a number for the analysis).90% CI: [39, 56.6]
Secondary
Occurrence of Drug-related Adverse Events
Percentage of participants with drug-related adverse events is reported.
Time frame: From start of drug of administration until end of trial, up to 59 days.
Population: Treated Set: Included all subjects who were randomised and treated with a dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg BI 765080 SC Injection (T) | Occurrence of Drug-related Adverse Events | 28.6 percentage of participants |
| 100 mg BI 765080 IV Infusion (R) | Occurrence of Drug-related Adverse Events | 7.1 percentage of participants |