A Study in Healthy Men to Test How BI 1358894 is Taken up in the Body and How Food Influences the Amount of BI 1358894 in the Blood

• BI 1358894 (Drug): Tablet
• BI 1358894 (C-14) intravenous solution (Drug): BI 1358894 mixed with \[carbon labelled (C-14)\] BI 1358894
• BI 1358894 (Drug): Oral suspension

Primary outcomes

• Part 1: Area Under the Concentration-time Curve of BI 1358894 Over the Time Interval From 0 to Infinity After i.v. Administration and After Oral Administration (AUC0-infinity) [Within 2 hours (h) before and at 15 minutes (min), 30 min, 1 h, 1.5, 2, 3, 4, 5, 5.083, 5.16, 5.25, 5.5, 5.75, 6, 6.5, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after oral dose of BI 1358894 on Day 1 of Period 1. Continues in description.]: Area under the concentration-time curve of BI 1358894 over the time interval from 0 to infinity after i.v. administration and after oral administration (AUC0-infinity) is reported. The values were calculated using the Analysis of variance (ANOVA) model which included effects accounting for the following sources of variation: 'subjects' and 'formulation'. The effect 'subjects' was considered as random, whereas 'formulation' was considered as fixed. Standard error is actually geometric standard error. Time Frame: For "BI 1358894 (C-14) 100 ug i.v" samples were collected at 5h, 5.083, 5.16, 5.25, 5.5, 5.75, 6, 6.5, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after oral dose of BI 1358894 on Day 1 of Period 1.
• Part 2: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 312 h (AUC 0-312) [Within 2 hours (h) before drug administration and at 15 minutes (min), 30 min, 1 h, 1.5, 2, 3, 4, 5, 6, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after administration of BI 1358894.]: Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 to 312 h (AUC 0-312) is reported. The values were calculated using the Analysis of variance (ANOVA) model which included effects accounting for the following sources of variation: 'sequence or block', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Standard error is actually geometric standard error.

Secondary outcomes

• Part 1: Maximum Measured Concentration of BI 1358894 in Plasma After i.v. Administration and After Oral Administration (Cmax) [Within 2 hours before and at 15 minutes (min), 30 min, 1 hour (h), 1.5, 2, 3, 4, 5, 5.083, 5.16, 5.25, 5.5, 5.75, 6, 6.5, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after oral dose of BI 1358894 on Day 1 of Period 1. Continues in description.]: Maximum measured concentration of BI 1358894 in plasma after i.v. administration and after oral administration(Cmax) is reported. Time Frame: For "BI 1358894 (C-14) 100 ug i.v" samples were collected at 5h, 5.083, 5.16, 5.25, 5.5, 5.75, 6, 6.5, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after oral dose of BI 1358894 on Day 1 of Period 1.
• Part 2: Maximum Measured Concentration of BI 1358894 in Plasma After Administration of the Oral Suspension (Cmax) [Within 2 hours (h) before drug administration and at 15 minutes (min), 30 min, 1 h, 1.5, 2, 3, 4, 5, 6, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after administration of BI 1358894.]: Maximum measured concentration of BI 1358894 in plasma after administration of the oral suspension (Cmax) is reported. The Analysis of variance (ANOVA) model included effects accounting for the following sources of variation: 'sequence or block', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Standard error is actually geometric standard error.
• Part 2: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity After Administration of the Oral Suspension (AUC0-infinity) [Within 2 hours (h) before drug administration and at 15 minutes (min), 30 min, 1 h, 1.5, 2, 3, 4, 5, 6, 7,8, 10, 12, 24, 34, 48, 72, 96, 144, 192, 240, 312 h after administration of BI 1358894.]: Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 extrapolated to infinity after administration of the oral suspension (AUC0-infinity) is reported. The Analysis of variance (ANOVA) model included effects accounting for the following sources of variation: 'sequence or block', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Standard error is actually geometric standard error.

Sex: Male, ages: 18 Years to 55 Years, accepts healthy volunteers

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 55 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
* Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 90 days after trial completion:
* Use of adequate contraception of the female partner, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device that started at least 2 months prior to first study drug administration or barrier method (e.g. diaphragm with spermicide) or,
* Sexually abstinent or
* A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or
* Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion or bilateral oophorectomy) or
* Postmenopausal female partner, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with FSH (follicle stimulating hormone) above 40 U/L and estradiol below 30 ng/L is confirmatory)

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 40 to 100 bpm
* C-reactive protein (CRP) > upper limit of normal (ULN), liver or kidney parameter above ULN
* 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
* 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
* Further exclusion criteria apply

Participant flow

Outcome results

• Part 1: Area Under the Concentration-time Curve of BI 1358894 Over the Time Interval From 0 to Infinity After i.v. Administration and After Oral Administration (AUC0-infinity) (Primary), Geometric least squares mean, hour*millimol/Liter/kilogram: BI 1358894 100 mg Tablet Fasted 96 +/- NA; BI 1358894 (C-14) 100 ug i.v 209 +/- NA
• Part 2: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 312 h (AUC 0-312) (Primary), Geometric least squares mean, hour* nanomol/Liter (h*nmol/L): BI 1358894 100 mg Oral Suspension Fasted 12217 +/- NA; BI 1358894 100 mg Oral Suspension Fed 17271 +/- NA
• Part 1: Maximum Measured Concentration of BI 1358894 in Plasma After i.v. Administration and After Oral Administration (Cmax) (Secondary), Geometric mean, nanomol/Liter (nmol/L): BI 1358894 100 mg Tablet Fasted 408 +/- 34.1; BI 1358894 (C-14) 100 ug i.v 0.847 +/- 28.8
• Part 2: Maximum Measured Concentration of BI 1358894 in Plasma After Administration of the Oral Suspension (Cmax) (Secondary), Geometric least squares mean, nanomol/Liter (nmol/L): BI 1358894 100 mg Oral Suspension Fasted 810 +/- NA; BI 1358894 100 mg Oral Suspension Fed 529 +/- NA
• Part 2: Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity After Administration of the Oral Suspension (AUC0-infinity) (Secondary), Geometric least squares mean, hour*nanomol/Liter (h*nmol/L): BI 1358894 100 mg Oral Suspension Fasted 13510 +/- NA; BI 1358894 100 mg Oral Suspension Fed 20052 +/- NA

Adverse events

Time frame: BI tablet = From treatment start until start of C14, up to 1 day. BI fed, BI fasted and BI C14 = day of treatment + 11 days Residual Effect Period (REP), up to 12 days.

Other adverse events by term

• Study Protocol (PDF, 2020-06-26)
• Statistical Analysis Plan (PDF, 2021-02-09)