Healthy
Conditions
Brief summary
Investigation of safety and tolerability of BI 1034020 in healthy male volunteers following intravenous (IV) infusion of subcutaneous (SC) injection of single doses and exploration of the pharmacokinetics and pharmacodynamics of BI 1034020 after single dosing and determination of the bioavailability of subcutaneous injections of BI 1034020
Interventions
DRUGBI 1034020
intravenous part
DRUGPlacebo to BI 1034020
intravenous part
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males based upon a complete medical history, including a physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, and clinical laboratory tests 2. Age within the range of 18 to 40 years 3. Body mass index within the range of 18.5 and 29.9 kg/m2 4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.
Exclusion criteria
1. Any finding in the medical examination (including blood pressure, pulse rate or electrocardiogram) deviating from normal and judged clinically relevant by the investigator. Pulse rate outside the range of 50-90 bpm or blood pressure outside the ranges of 90-140 for systolic and 50-90 mmHg for diastolic blood pressure if confirmed by repeat measurement 2. Any evidence of a clinically relevant concomitant disease. 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders. 4. Surgery of the gastrointestinal tract (except appendectomy). 5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders. 6. History of relevant orthostatic hypotension, fainting spells or blackouts. 7. Chronic or relevant acute infections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug Related Adverse Events | from the first drug administration to end of trial, up to 50 days | Percentage of subjects with investigator defined drug-related adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 2h before study drug administration and 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 168h, 336h, 504h, 672h, 840h and 1008h after drug administration on day 1. | Maximum measured concentration of BI 1034020 in plasma (Cmax). |
| AUC0-inf | 2h before study drug administration and 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 168h, 336h, 504h, 672h, 840h and 1008h after drug administration on day 1. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). AUC0-inf could be assessed only in 50 mg iv dose group as terminal phase was below lower limit of quantification (BLQ) for other dose groups. Therefore dose proportionality for AUC0-inf could not be performed in this trial. |
| AUC0-tz | 2h before study drug administration and 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 168h, 336h, 504h, 672h, 840h and 1008h after drug administration on day 1. | Area under the concentration-time curve of the analyte in the plasma over the time interval from 0 to the last measurable time point of the dose (AUC0-tz ). |
Countries
Germany
Participant flow
Recruitment details
This trial was initiated at two centres. As one of the trial centres did not enrol any subjects by the time of premature termination of the trial; the trial was conducted only at one centre.
Pre-assignment details
Partially randomised, placebo-controlled within dose groups, single-blind, single rising dose, multiple centres (dose escalation intravenous \[iv\] bridging to subcutaneous \[sc\] in parallel). 35 subjects were enrolled and 32 subjects were treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single dose administration of placebo to BI 1034020 through solution for intravenous (iv) infusion in the morning. | 8 |
| BI 1034020 (5 mg/25 mL - iv) Single dose administration of BI 1034020 (5 mg) diluted with 25mL solution for intravenous (iv) infusion in the morning. | 6 |
| BI 1034020 (10 mg/25 mL - iv) Single dose administration of BI 1034020 (10 mg) diluted with 25mL solution for intravenous (iv) infusion in the morning. | 6 |
| BI 1034020 (20 mg/25 mL - iv) Single dose administration of BI 1034020 (20 mg) diluted with 25mL solution for intravenous (iv) infusion in the morning. | 5 |
| BI 1034020 (50 mg/25 mL - iv) Single dose administration of BI 1034020 (50 mg) diluted with 25mL solution for intravenous (iv) infusion in the morning. | 6 |
| BI 1034020 (100 mg/25 mL - iv) Single dose administration of BI 1034020 (5 mg) diluted with 25mL solution for intravenous (iv) infusion in the morning. | 1 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Not treated | 2 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | BI 1034020 (5 mg/25 mL - iv) | BI 1034020 (10 mg/25 mL - iv) | BI 1034020 (20 mg/25 mL - iv) | BI 1034020 (50 mg/25 mL - iv) | BI 1034020 (100 mg/25 mL - iv) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 26.5 Year STANDARD_DEVIATION 4.3 | 32.5 Year STANDARD_DEVIATION 3.9 | 33.2 Year STANDARD_DEVIATION 3.4 | 31.4 Year STANDARD_DEVIATION 4 | 34.3 Year STANDARD_DEVIATION 4 | 23.0 Year | 31.0 Year STANDARD_DEVIATION 4.9 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 1 Participants | 32 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 3 / 6 | 4 / 6 | 3 / 5 | 5 / 6 | 1 / 1 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 1 / 1 |
Outcome results
Primary
Percentage of Subjects With Drug Related Adverse Events
Percentage of subjects with investigator defined drug-related adverse events
Time frame: from the first drug administration to end of trial, up to 50 days
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug Related Adverse Events | 37.5 percentage of participants |
| BI 1034020 (5 mg/25 mL - iv) | Percentage of Subjects With Drug Related Adverse Events | 33.3 percentage of participants |
| BI 1034020 (10 mg/25 mL - iv) | Percentage of Subjects With Drug Related Adverse Events | 33.3 percentage of participants |
| BI 1034020 (20 mg/25 mL - iv) | Percentage of Subjects With Drug Related Adverse Events | 0.0 percentage of participants |
| BI 1034020 (50 mg/25 mL - iv) | Percentage of Subjects With Drug Related Adverse Events | 50.0 percentage of participants |
| BI 1034020 (100 mg/25 mL - iv) | Percentage of Subjects With Drug Related Adverse Events | 100.0 percentage of participants |
Secondary
AUC0-inf
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). AUC0-inf could be assessed only in 50 mg iv dose group as terminal phase was below lower limit of quantification (BLQ) for other dose groups. Therefore dose proportionality for AUC0-inf could not be performed in this trial.
Time frame: 2h before study drug administration and 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 168h, 336h, 504h, 672h, 840h and 1008h after drug administration on day 1.
Population: Pharmacokinetic set (PKS):
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-inf | 314 μg*h/mL | Geometric Coefficient of Variation 7.66 |
Secondary
AUC0-tz
Area under the concentration-time curve of the analyte in the plasma over the time interval from 0 to the last measurable time point of the dose (AUC0-tz ).
Time frame: 2h before study drug administration and 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 168h, 336h, 504h, 672h, 840h and 1008h after drug administration on day 1.
Population: Pharmacokinetic set (PKS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-tz | 7.30 μg*h/mL | Geometric Coefficient of Variation 9.6 |
| BI 1034020 (5 mg/25 mL - iv) | AUC0-tz | 20.1 μg*h/mL | Geometric Coefficient of Variation 28.5 |
| BI 1034020 (10 mg/25 mL - iv) | AUC0-tz | 83.7 μg*h/mL | Geometric Coefficient of Variation 94.4 |
| BI 1034020 (20 mg/25 mL - iv) | AUC0-tz | 242 μg*h/mL | Geometric Coefficient of Variation 15.4 |
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of BI 1034020 following iv administration of single rising doses of 5 mg, 10 mg, 20 mg and 50 mg for AUClast was analysed.95% CI: [1.3426, 1.7833]
Secondary
Cmax
Maximum measured concentration of BI 1034020 in plasma (Cmax).
Time frame: 2h before study drug administration and 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h, 168h, 336h, 504h, 672h, 840h and 1008h after drug administration on day 1.
Population: Pharmacokinetic Set (PKS): This subject set included all subjects in the treated set who provide at least 1 observation for at least 1 secondary Pharmacokinetic (PK) endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax | 1.50 μg/mL | Geometric Coefficient of Variation 8.69 |
| BI 1034020 (5 mg/25 mL - iv) | Cmax | 3.30 μg/mL | Geometric Coefficient of Variation 17.6 |
| BI 1034020 (10 mg/25 mL - iv) | Cmax | 6.90 μg/mL | Geometric Coefficient of Variation 15.7 |
| BI 1034020 (20 mg/25 mL - iv) | Cmax | 17.2 μg/mL | Geometric Coefficient of Variation 11.5 |
Comparison: This was non confirmatory testing (Single dose). Dose proportionality of BI 1034020 following iv administration of single rising doses of 5 mg, 10 mg, 20 mg and 50 mg for Cmax was analysed.95% CI: [0.9901, 1.1308]