Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety, tolerability, and pharmacokinetics of BI 765080 in healthy male subjects following intravenous administration of single rising doses.
Interventions
DRUGBI 765080
BI 765080
DRUGPlacebo
Placebo; 0.9% saline for injection
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 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 (BP, PR), 12-lead ECG, and clinical laboratory tests * Age of 18 to 50 years (inclusive) * 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 GCP and local legislation
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 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 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 * A positive poly chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clinical symptoms suggestive for this disease on Day -2. * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug-related Adverse Events | Up to 87 days | Percentage of subjects with drug-related adverse events is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) prior to administration of BI 765080 and 30 minutes (min), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 144h, 312h, 480h, 648h, 1320h and 1992h after administration of BI 765080. | Area under the concentration-time curve of BI 765080 in serum over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented. |
| Maximum Measured Concentration of BI 765080 in Serum (Cmax) | Within 3 hours (h) prior to administration of BI 765080 and 30 minutes (min), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 144h, 312h, 480h, 648h, 1320h and 1992h after administration of BI 765080. | Maximum measured concentration of BI 765080 in serum (Cmax) is presented. |
Countries
Belgium
Participant flow
Recruitment details
This is a Phase I, single-blind, randomized, placebo-controlled, parallel-group design trial to investigate safety, tolerability, and pharmacokinetics of BI 765080 in healthy male subjects following intravenous administration of single rising doses.
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 |
|---|---|
| 1 mg BI 765080 Group Subjects received a single dose of 1 milligram (mg) BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 6 |
| 10 mg BI 765080 Group Subjects received a single dose of 10 milligrams (mg) BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 6 |
| 25 mg BI 765080 Group Subjects received a single dose of 25 milligrams (mg) BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 6 |
| 50 mg BI 765080 Group Subjects received a single dose of 50 milligrams (mg) BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 6 |
| 100 mg BI 765080 Group Subjects received a single dose of 100 milligrams (mg) BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 6 |
| 200 mg BI 765080 Group Subjects received a single dose of 200 milligrams (mg) BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 6 |
| Placebo Group Subjects received a single dose of placebo matching BI 765080 as a 30 minutes (min) intravenous infusion on Day 1. | 12 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 1 mg BI 765080 Group | Total | Placebo Group | 200 mg BI 765080 Group | 100 mg BI 765080 Group | 50 mg BI 765080 Group | 25 mg BI 765080 Group | 10 mg BI 765080 Group |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 6.8 | 35.1 Years STANDARD_DEVIATION 8 | 32.8 Years STANDARD_DEVIATION 6.6 | 37.5 Years STANDARD_DEVIATION 11.3 | 32.3 Years STANDARD_DEVIATION 4.9 | 38.3 Years STANDARD_DEVIATION 9.9 | 31.2 Years STANDARD_DEVIATION 7.7 | 33.7 Years STANDARD_DEVIATION 4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 47 Participants | 12 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 48 Participants | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 2 / 6 | 1 / 6 | 1 / 6 | 5 / 6 | 0 / 6 | 2 / 6 | 5 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 |
Outcome results
Primary
Percentage of Subjects With Drug-related Adverse Events
Percentage of subjects with drug-related adverse events is presented.
Time frame: Up to 87 days
Population: Treated set (TS): all subjects who were randomised and treated with at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 mg BI 765080 Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
| 10 mg BI 765080 Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
| 25 mg BI 765080 Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
| 50 mg BI 765080 Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
| 100 mg BI 765080 Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
| 200 mg BI 765080 Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
| Placebo Group | Percentage of Subjects With Drug-related Adverse Events | 0 Percentage of Participants |
Secondary
Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 765080 in serum over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented.
Time frame: Within 3 hours (h) prior to administration of BI 765080 and 30 minutes (min), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 144h, 312h, 480h, 648h, 1320h and 1992h after administration of BI 765080.
Population: Pharmacokinetic parameter analysis 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 PK non-evaluability (as specified below). Thus, a subject was included in the PKS, even if he contributed only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1 mg BI 765080 Group | Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 4950 hours*nanograms/milliLitres (h*ng/mL) | Geometric Coefficient of Variation 48.4 |
| 10 mg BI 765080 Group | Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 258000 hours*nanograms/milliLitres (h*ng/mL) | Geometric Coefficient of Variation 20.6 |
| 25 mg BI 765080 Group | Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 973000 hours*nanograms/milliLitres (h*ng/mL) | Geometric Coefficient of Variation 16.2 |
| 50 mg BI 765080 Group | Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2530000 hours*nanograms/milliLitres (h*ng/mL) | Geometric Coefficient of Variation 39.9 |
| 100 mg BI 765080 Group | Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 7180000 hours*nanograms/milliLitres (h*ng/mL) | Geometric Coefficient of Variation 24.7 |
| 200 mg BI 765080 Group | Area Under the Concentration-time Curve of BI 765080 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 14900000 hours*nanograms/milliLitres (h*ng/mL) | Geometric Coefficient of Variation 21.8 |
Secondary
Maximum Measured Concentration of BI 765080 in Serum (Cmax)
Maximum measured concentration of BI 765080 in serum (Cmax) is presented.
Time frame: Within 3 hours (h) prior to administration of BI 765080 and 30 minutes (min), 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 144h, 312h, 480h, 648h, 1320h and 1992h after administration of BI 765080.
Population: Pharmacokinetic parameter analysis 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 PK non-evaluability (as specified below). Thus, a subject was included in the PKS, even if he contributed only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1 mg BI 765080 Group | Maximum Measured Concentration of BI 765080 in Serum (Cmax) | 274 nanograms/milliLitres (ng/mL) | Geometric Coefficient of Variation 21.4 |
| 10 mg BI 765080 Group | Maximum Measured Concentration of BI 765080 in Serum (Cmax) | 3490 nanograms/milliLitres (ng/mL) | Geometric Coefficient of Variation 11 |
| 25 mg BI 765080 Group | Maximum Measured Concentration of BI 765080 in Serum (Cmax) | 8230 nanograms/milliLitres (ng/mL) | Geometric Coefficient of Variation 14.9 |
| 50 mg BI 765080 Group | Maximum Measured Concentration of BI 765080 in Serum (Cmax) | 16900 nanograms/milliLitres (ng/mL) | Geometric Coefficient of Variation 29 |
| 100 mg BI 765080 Group | Maximum Measured Concentration of BI 765080 in Serum (Cmax) | 35400 nanograms/milliLitres (ng/mL) | Geometric Coefficient of Variation 13.7 |
| 200 mg BI 765080 Group | Maximum Measured Concentration of BI 765080 in Serum (Cmax) | 64500 nanograms/milliLitres (ng/mL) | Geometric Coefficient of Variation 11.6 |