Healthy
Conditions
Brief summary
The objective of this trial is to investigate the safety, tolerability and pharmacokinetics of BI 894416 in healthy Japanese male subjects.
Interventions
DRUGBI 894416
BI 894416
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male subjects according to the assessment of the investigator, as based on a complete medical history, including a medical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests 2. Japanese ethnicity, according to the following criteria: \- born in Japan, have lived outside of Japan \<10 years, and have parents and grandparents who are Japanese 3. Age of 20 to 45 years (inclusive) at screening 4. BMI of 18.5 to 25.0 kg/m2 (inclusive) at screening 5. Signed and dated written informed consent prior to admission to the trial, in accordance with Good Clinical Practice (GCP) and local legislation 6. Subjects who agree to minimize the risk of making their partner pregnant by fulfilling any of the following criteria starting from the first administration of trial medication until 90 days after last administration of trial medication * Use of adequate contraception, any of the following methods plus condom: intrauterine device, combined oral contraceptives that started at least 2 months prior to the first drug administration * Vasectomized (vasectomy at least 1 year prior to enrolment) * Surgical sterilization (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner
Exclusion criteria
1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator 2. 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 3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator 5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication, except appendectomy or simple hernia repair 7. Diseases of the central nervous system, including but not limited to, any kind of seizures or stroke, and other relevant neurological or psychiatric disorders 8. History of relevant orthostatic hypotension, fainting spells, or blackouts Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug Related Adverse Events | From drug administration until end of follow-up, up to 17 days. | The percentage of participants with drug related adverse events was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 1 hour (h) before drug administration and at 15 minutes (min), 30min, 45min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity was reported. |
| Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | Within 1 hour (h) before drug administration and at 15 minutes (min), 30min, 45min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. | Maximum measured concentration of BI 894416 in plasma was reported. |
Countries
Japan
Participant flow
Recruitment details
This single-blind, randomised, placebo-controlled within dose group study investigated the safety, tolerability, and pharmacokinetics of single rising oral doses of BI 894416 versus placebo in healthy male Japanese subjects followed by 48 hours close medical surveillance and 2 weeks of follow-up period thereafter. This trial was prematurely terminated due to decision of sponsor.
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 |
|---|---|
| BI 894416 25mg 1 tablet of 25 milligrams (mg) BI 894416 was administered orally as single dose with 240 milliliters of water after an overnight fast of at least 10 hours on day 1, followed by at least 48 hours close medical surveillance, followed by 2 weeks of follow-up period. | 6 |
| Placebo Matching placebo was administered orally as single dose with 240 milliliters of water after an overnight fast of at least 10 hours on day 1, followed by at least 48 hours close medical surveillance, followed by 2 weeks of follow-up period. | 2 |
| Total | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | BI 894416 25mg |
|---|---|---|---|
| Age, Continuous | 31.5 Years STANDARD_DEVIATION 12 | 31.5 Years STANDARD_DEVIATION 8 | 31.5 Years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 8 Participants | 6 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 | 2 Participants | 8 Participants | 6 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 | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 2 | 0 / 8 |
| other Total, other adverse events | 1 / 6 | 1 / 2 | 2 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 2 | 0 / 8 |
Outcome results
Primary
Percentage of Participants With Drug Related Adverse Events
The percentage of participants with drug related adverse events was reported.
Time frame: From drug administration until end of follow-up, up to 17 days.
Population: Treated set (TS): The treated set includes all subjects who were randomized and treated with at least one dose of investigational medicinal product. The treatment assignment will be determined based on the first treatment the subjects received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 894416 25mg | Percentage of Participants With Drug Related Adverse Events | 16.7 Percentage of participants |
| Placebo | Percentage of Participants With Drug Related Adverse Events | 0.0 Percentage of participants |
Secondary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity was reported.
Time frame: Within 1 hour (h) before drug administration and at 15 minutes (min), 30min, 45min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the treated set who provide at least one PK endpoint that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject will be included in the PKS, even if he contributes only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 894416 25mg | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3550 hour * nanomole / liter | Geometric Coefficient of Variation 26.6 |
Secondary
Maximum Measured Concentration of BI 894416 in Plasma (Cmax)
Maximum measured concentration of BI 894416 in plasma was reported.
Time frame: Within 1 hour (h) before drug administration and at 15 minutes (min), 30min, 45min, 1h, 1h30min, 2h, 2h30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This set includes all subjects in the treated set who provide at least one PK endpoint that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject will be included in the PKS, even if he contributes only one PK parameter value for one period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 894416 25mg | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | 708 nanomole / liter | Geometric Coefficient of Variation 25 |