Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 1358894 in healthy male subjects following oral administration of single rising doses.
Interventions
DRUGPlacebo
For each dose group a placebo group was given matching placebo tablets, participants were randomized within each dose group in a 3:1 ratio (active drug:placebo), tablets taken orally with \ 240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
DRUGDose group 1 - 50 mg BI 1358894
2 film-coated tablets of 25 milligram (mg) BI 1358894 taken orally with \ 240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
DRUGDose group 2 - 100 mg BI 1358894
1 film-coated tablet of 100 milligram BI 1358894 taken orally with \ 240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
DRUGDose group 3 - 200 mg BI 1358894
2 film-coated tablets of 100 milligram BI 1358894 taken orally with \ 240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours).
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 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 (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests * 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 * Age of 20 to 45 years (inclusive) at screening * Body mass index (BMI) of 18.5 to 25.0 kg/m2 (inclusive) at screening * Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation * Willingness to comply with contraception requirements. Subjects who are sexually active must use with their female partner, adequate contraception throughout the study and until three months after the last administration of trial medication. Adequate methods are: * A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or * Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner or * The use of condoms, if the female partner uses an adequate contraception method in addition, e.g., intrauterine device (IUD), hormonal contraception (e.g., implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g., diaphragm with spermicide) Unprotected sexual intercourse with a pregnant female partner is not allowed throughout the study and until three months after the last administration of trial medication.
Exclusion criteria
* Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (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 50 to 90 bpm * C-Reactive Protein (CRP) \> upper limit of normal (ULN), erythrocyte sedimentation rate (ESR) ≥ 15 millimeters/hour, liver and kidney parameter above ULN, other 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 * Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair) * 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 including viral hepatitis, human immunodeficiency virus (HIV) and/or syphilis. (Subject with positive Hepatitis B core antibody will not be allowed to participate in this trial) * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation) * Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) * Inability to refrain from smoking on specified trial days * Alcohol abuse (consumption of more 30 g per day for males) * Drug abuse or positive drug screening * Blood donation of more than 400 mL within 12 weeks or 200 mL within 30 days or plasma donation within 2 weeks prior to administration or intended blood donation during the trial * Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial * Inability to comply with the dietary regimen of the trial site * A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening * A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour) * Any suicidal ideation of type 2 to 5 on the C-SSRS in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug Related Adverse Events (AEs). | Up to 14 days for 50 mg BI 1358894, 100 mg BI 1358894 and placebo. Up to 33 days for 200 mg BI 1358894. | Percentage of subjects with drug related adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz). | 2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3. | AUC0-tz (area under the concentration-time curve of BI 1358894 in plasma over the time interval from the time of administration to the last quantifiable data time point tz). |
| Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3. | Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 extrapolated to infinity. |
| Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3. | Maximum measured concentration of BI 1358894 in plasma. |
Countries
Japan
Participant flow
Recruitment details
This study tests the safety, tolerability and pharmacokinetics of single rising oral doses of BI 1358894 in healthy Japanese male subjects (double blind, randomised, placebo-controlled parallel dose group design)
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 |
|---|---|
| Placebo For each dose group a placebo group was given matching placebo tablets, participants were randomized within each dose group in a 3:1 ratio (active drug:placebo), tablets taken orally with \
240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours). | 6 |
| Dose Group 1 - 50 mg BI 1358894 2 film-coated tablets of 25 milligram (mg) BI 1358894 taken orally with \
240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours). | 6 |
| Dose Group 2 - 100 mg BI 1358894 1 film-coated tablet of 100 milligram BI 1358894 taken orally with \
240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours). | 6 |
| Dose Group 3 - 200 mg BI 1358894 2 film-coated tablets of 100 milligram BI 1358894 taken orally with \
240 milliliter of water 30 minutes after a standard high-fat, high-calorie meal (after an overnight fast of 10 hours). | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | Dose Group 1 - 50 mg BI 1358894 | Dose Group 2 - 100 mg BI 1358894 | Dose Group 3 - 200 mg BI 1358894 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 7.1 | 26.3 years STANDARD_DEVIATION 8.4 | 32.3 years STANDARD_DEVIATION 8.4 | 29.8 years STANDARD_DEVIATION 7 | 30.0 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Percentage of Subjects With Drug Related Adverse Events (AEs).
Percentage of subjects with drug related adverse events (AEs).
Time frame: Up to 14 days for 50 mg BI 1358894, 100 mg BI 1358894 and placebo. Up to 33 days for 200 mg BI 1358894.
Population: Treated set: This set included data from all subjects who received at least one dose of trial drug. The TS was used for safety analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug Related Adverse Events (AEs). | 0 Percentage |
| Dose Group 1 - 50 mg BI 1358894 | Percentage of Subjects With Drug Related Adverse Events (AEs). | 0 Percentage |
| Dose Group 2 - 100 mg BI 1358894 | Percentage of Subjects With Drug Related Adverse Events (AEs). | 16.7 Percentage |
| Dose Group 3 - 200 mg BI 1358894 | Percentage of Subjects With Drug Related Adverse Events (AEs). | 33.3 Percentage |
Secondary
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3.
Population: Pharmacokinetic Set (PKS): This set included all subjects from the treated set who provide at least one Pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK, or due to PK non-evaluability, even subjects contributing with only 1 PK parameter were included in PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 6960 nanomole (nmol)* hour (h) / liter (L) | Geometric Coefficient of Variation 16.5 |
| Dose Group 1 - 50 mg BI 1358894 | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 15800 nanomole (nmol)* hour (h) / liter (L) | Geometric Coefficient of Variation 20.8 |
| Dose Group 2 - 100 mg BI 1358894 | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 33600 nanomole (nmol)* hour (h) / liter (L) | Geometric Coefficient of Variation 26.1 |
Secondary
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).
AUC0-tz (area under the concentration-time curve of BI 1358894 in plasma over the time interval from the time of administration to the last quantifiable data time point tz).
Time frame: 2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3.
Population: Pharmacokinetic Set (PKS): This set included all subjects from the treated set who provide at least one Pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK, or due to PK non-evaluability, even subjects contributing with only 1 PK parameter were included in PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz). | 6320 nanomole (nmol)* hour (h) / liter (L) | Geometric Coefficient of Variation 15 |
| Dose Group 1 - 50 mg BI 1358894 | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz). | 13700 nanomole (nmol)* hour (h) / liter (L) | Geometric Coefficient of Variation 23.5 |
| Dose Group 2 - 100 mg BI 1358894 | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz). | 32200 nanomole (nmol)* hour (h) / liter (L) | Geometric Coefficient of Variation 26 |
Secondary
Maximum Measured Concentration of BI 1358894 in Plasma (Cmax)
Maximum measured concentration of BI 1358894 in plasma.
Time frame: 2 hours before and 0.17, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168*, 192, 240#, 336#, 504#, 672# hours following treatment. *only dose groups 1 and 2, #only dose group 3.
Population: Pharmacokinetic Set (PKS): This set included all subjects from the treated set who provide at least one Pharmacokinetic (PK) endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK, or due to PK non-evaluability, even subjects contributing with only 1 PK parameter were included in PKS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 224 nanomole (nmol) / liter (L) | Geometric Coefficient of Variation 14.2 |
| Dose Group 1 - 50 mg BI 1358894 | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 470 nanomole (nmol) / liter (L) | Geometric Coefficient of Variation 22.3 |
| Dose Group 2 - 100 mg BI 1358894 | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 904 nanomole (nmol) / liter (L) | Geometric Coefficient of Variation 10.9 |