Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of single rising doses of BI 473494 in healthy male subjects. The secondary objective is the exploration of PK including dose proportionality, and PD of BI 473494 after single dosing.
Interventions
DRUGBI 473494
Solution for injection
DRUGPlacebo
Solution 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 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the assessment of the investigator, 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 45 years (incl.) * Body Mass Index \[BMI\] of 20.0 to 29.9 kg/m2 (incl.) * 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 Blood Pressure \[BP\], Pulse Rate \[PR\] or Electrocardiogram \[ECG\]) is deviating from normal and judged 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 50 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 judged as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation) * Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events (AEs) Analysed as Investigator Defined Drug-related AEs | From drug administration until End of trial (EOT), up to 40 days. | Percentage of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 473494 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | Pharmacokinetic samples were taken 1:00 hour:minute (h:m) pre-dose and 3:00, 6:00, 9:00, 12:00, 15:00 , 22:00, 24:00, 28:00, 34:00, 39:00, 48:00, 60:00, 72:00, 96:00, 120:00, 168:00, 240:00, 336:00, 504:00 and 672:00 h:m after drug administration on day 1 | AUC0-tz, area under the concentration-time curve of BI 473494 over the time interval from 0 to the last quantifiable time point is presented. |
| Maximum Measured Concentration of BI 473494 (Cmax) | Pharmacokinetic samples were taken 1:00 hour:minute (h:m) pre-dose and 3:00, 6:00, 9:00, 12:00, 15:00 , 22:00, 24:00, 28:00, 34:00, 39:00, 48:00, 60:00, 72:00, 96:00, 120:00, 168:00, 240:00, 336:00, 504:00 and 672:00 h:m after drug administration on day 1 | Cmax, maximum measured concentration of BI 473494 is presented. |
Countries
Germany
Participant flow
Recruitment details
It was planned to include healthy participants in this single-rising dose trial with a single-blind, partially randomised, placebo controlled and parallel group design. They were recruited from the volunteer's pool of the study site.
Pre-assignment details
All participants were screened for eligibility to participate in the trial by the trial site. The site ensured that the participants met all strictly implemented inclusion/exclusion criteria. Participants were not to be assigned to treatment groups if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching BI 473494 Healthy participants were administered a single dose of placebo matching BI 473494 solution via subcutaneous injection. | 4 |
| BI 473494 35 μg Healthy participants were administered a single dose of 35 micrograms (μg) BI 473494 solution via subcutaneous injection. | 6 |
| BI 473494 75 μg Healthy participants were administered a single dose of 75 micrograms (μg) BI 473494 solution via subcutaneous injection. | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo Matching BI 473494 | BI 473494 35 μg | BI 473494 75 μg | Total |
|---|---|---|---|---|
| Age, Continuous | 34.3 Years STANDARD_DEVIATION 5.9 | 34.0 Years STANDARD_DEVIATION 7.4 | 30.2 Years STANDARD_DEVIATION 6.8 | 32.6 Years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 4 | 2 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 1 / 6 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events (AEs) Analysed as Investigator Defined Drug-related AEs
Percentage of participants with drug-related adverse events (AEs) analysed as investigator defined drug-related AEs is presented. Medical judgment was used to determine the relationship between the AEs and the study medication, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.
Time frame: From drug administration until End of trial (EOT), up to 40 days.
Population: Treated set (TS) : The TS included all subjects who were dispensed study medication and were documented to have taken at least one dose of BI 473494.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 473494 | Percentage of Participants With Drug-related Adverse Events (AEs) Analysed as Investigator Defined Drug-related AEs | 0.0 Percentage of participants (%) |
| BI 473494 35 μg | Percentage of Participants With Drug-related Adverse Events (AEs) Analysed as Investigator Defined Drug-related AEs | 0.0 Percentage of participants (%) |
| BI 473494 75 μg | Percentage of Participants With Drug-related Adverse Events (AEs) Analysed as Investigator Defined Drug-related AEs | 16.7 Percentage of participants (%) |
Secondary
Area Under the Concentration-time Curve of BI 473494 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)
AUC0-tz, area under the concentration-time curve of BI 473494 over the time interval from 0 to the last quantifiable time point is presented.
Time frame: Pharmacokinetic samples were taken 1:00 hour:minute (h:m) pre-dose and 3:00, 6:00, 9:00, 12:00, 15:00 , 22:00, 24:00, 28:00, 34:00, 39:00, 48:00, 60:00, 72:00, 96:00, 120:00, 168:00, 240:00, 336:00, 504:00 and 672:00 h:m after drug administration on day 1
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects from the TS who received study medication and provided at least one secondary PK parameter that was not excluded due to important protocol deviations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 473494 | Area Under the Concentration-time Curve of BI 473494 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | 162 Nanomole*Hours/Litre (nmol*h/L) | Geometric Coefficient of Variation 24.8 |
| BI 473494 35 μg | Area Under the Concentration-time Curve of BI 473494 Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz) | 546 Nanomole*Hours/Litre (nmol*h/L) | Geometric Coefficient of Variation 18.5 |
Secondary
Maximum Measured Concentration of BI 473494 (Cmax)
Cmax, maximum measured concentration of BI 473494 is presented.
Time frame: Pharmacokinetic samples were taken 1:00 hour:minute (h:m) pre-dose and 3:00, 6:00, 9:00, 12:00, 15:00 , 22:00, 24:00, 28:00, 34:00, 39:00, 48:00, 60:00, 72:00, 96:00, 120:00, 168:00, 240:00, 336:00, 504:00 and 672:00 h:m after drug administration on day 1
Population: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects from the TS who received study medication and provided at least one secondary PK parameter that was not excluded due to important protocol deviations with respect to the statistical evaluation of PK endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 473494 | Maximum Measured Concentration of BI 473494 (Cmax) | 0.82 Nanomole/Litre (nmol/L) | Geometric Coefficient of Variation 23.1 |
| BI 473494 35 μg | Maximum Measured Concentration of BI 473494 (Cmax) | 1.88 Nanomole/Litre (nmol/L) | Geometric Coefficient of Variation 17.5 |