Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of a single dose of BI 1358894 administered as tablet formulation 2 (TF2a, TF2b) under fasted conditions compared with the tablet formulation 1 (TF1) of BI 1358894 under fed conditions following oral administration and to investigate the effect of food on the exposure with TF2 (TF2a, TF2b).
Interventions
DRUGBI 1358894 (B)
Tablet formulation 2 (TF2a), fed
DRUGBI 1358894 (C)
Tablet formulation 2 (TF2a), fasted
DRUGBI 1358894 (D)
Tablet formulation 2 (TF2b), fed
DRUGBI 1358894 (E)
Tablet formulation 2 (TF2b), fasted
DRUGBI 1358894 (A)
Tablet formulation 1 (TF1), fed
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 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. * Age of 18 to 50 years (inclusive) * Body mass index (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 Good Clinical Practice (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 30 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 (IUD) that started at least 2 months prior to first study drug administration, or barrier method (e.g. diaphragm with spermicide) * Sexually abstinent * A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) * Surgically sterilised female partner (including hysterectomy, bilateral tubal occlusion or bilateral oophorectomy)
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/h, liver or kidney parameter above ULN, or any 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 and 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 * 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 than 30 g per day) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days of planned administration of trial medication 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 Columbia Suicidal Severity Rating scale (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 |
|---|---|---|
| Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period. | Maximum measured concentration of BI 1358894 in plasma (Cmax). |
| 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) | Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period. | 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 to 72 Hours (AUC0-72) | Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration in each treatment period. | Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 to 72 hours (AUC0-72). |
Countries
Germany
Participant flow
Recruitment details
This open-label, single-dose, randomized, incomplete blocks crossover design study in healthy male was to test if taking different tablet formulations (TF1, TF2a, and TF2b) of BI 1358894 with or without food influences the amount of BI 1358894 in the blood.
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 |
|---|---|
| TF1 Fed (A)-TF2a Fed (B)-TF2a Fasted (C) 1 tablet of 100 milligram (mg) BI 1358894 was administrated as a single oral dose with 240 milliliter (mL) water 30 minutes (min) after a high-fat, high-calorie breakfast as treatment A (TF1; fed conditions) followed by a washout period of at least 17 days, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a fed conditions) as treatment B followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 hours (h) (TF2a fasted conditions) as treatment C. | 2 |
| TF2b Fed (D)-TF1 Fed (A)-TF2a Fed (B) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D followed by at least 17 days of washout, followed by 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a; fed conditions) as treatment B. | 2 |
| TF2b Fasted (E)-TF2a Fed (B)-TF1 Fed (A) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E followed by washout period of at least 17 days, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a; fed conditions) as treatment B followed by at least 17 days of washout, followed by 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A. | 2 |
| TF2a Fasted (C)- TF1 Fed (A)-TF2b Fed (D) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2a; fasted conditions) as treatment C followed by washout period of at least 17 days, followed by 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D. | 2 |
| TF1 Fed (A)- TF2b Fasted (E)- TF2a Fasted (C) 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2a; fasted conditions) as treatment C. | 2 |
| TF2b Fasted (E)-TF2b Fed (D)- TF1 Fed (A) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D followed by at least 17 days of washout, followed by 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A. | 2 |
| TF2a Fed (B)- TF2a Fasted (C)-TF2b Fed (D) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a; fed conditions) as treatment B followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2a; fasted conditions) as treatment C followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D. | 2 |
| TF2a Fasted(C)-TF2b Fasted(E)-TF2a Fed(B) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2a; fasted conditions) as treatment C followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a; fed conditions) as treatment B. | 2 |
| TF2a Fed(B)-TF2b Fed(D)-TF2b Fasted(E) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a; fed conditions) as treatment B followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E. | 2 |
| TF2b Fed(D)-TF2a Fasted(C)-TF2b Fasted(E) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2a; fasted conditions) as treatment C followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E. | 2 |
| TF2a Fasted(C)-TF2a Fed(B)-TF1 Fed(A) 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2a; fasted conditions) as treatment C followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2a; fed conditions) as treatment B followed by at least 17 days of washout, followed by 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A. | 2 |
| TF1 Fed (A)- TF2b Fasted (E)-TF2b Fed (D) 1 tablet of 100 mg BI 1358894 was administrated as a single oral dose with 240mL water 30 min after a high-fat, high-calorie breakfast (TF1; fed conditions) as treatment A followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water after an overnight fast of at least 10 h (TF2b; fasted conditions) as treatment E followed by at least 17 days of washout, followed by 2 tablets of 50mg BI 1358894 (total: 100mg) administrated as a single oral dose with 240 mL water 30 min after a high-fat, high-calorie breakfast (TF2b; fed conditions) as treatment D. | 2 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Washout Period 2 | Met discontinuation criterion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | TF1 Fed (A)-TF2a Fed (B)-TF2a Fasted (C) | TF2b Fed (D)-TF1 Fed (A)-TF2a Fed (B) | TF2b Fasted (E)-TF2a Fed (B)-TF1 Fed (A) | TF2a Fasted (C)- TF1 Fed (A)-TF2b Fed (D) | TF1 Fed (A)- TF2b Fasted (E)- TF2a Fasted (C) | TF2b Fasted (E)-TF2b Fed (D)- TF1 Fed (A) | TF2a Fed (B)- TF2a Fasted (C)-TF2b Fed (D) | TF2a Fasted(C)-TF2b Fasted(E)-TF2a Fed(B) | TF2a Fed(B)-TF2b Fed(D)-TF2b Fasted(E) | TF2b Fed(D)-TF2a Fasted(C)-TF2b Fasted(E) | TF2a Fasted(C)-TF2a Fed(B)-TF1 Fed(A) | TF1 Fed (A)- TF2b Fasted (E)-TF2b Fed (D) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 39.5 Years STANDARD_DEVIATION 12 | 46.0 Years STANDARD_DEVIATION 2.8 | 43.0 Years STANDARD_DEVIATION 7.1 | 46.0 Years STANDARD_DEVIATION 0 | 41.0 Years STANDARD_DEVIATION 11.3 | 46.5 Years STANDARD_DEVIATION 0.7 | 33.0 Years STANDARD_DEVIATION 18.4 | 46.0 Years STANDARD_DEVIATION 5.7 | 48.5 Years STANDARD_DEVIATION 2.1 | 35.5 Years STANDARD_DEVIATION 20.5 | 35.5 Years STANDARD_DEVIATION 10.6 | 47.0 Years STANDARD_DEVIATION 4.2 | 42.3 Years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 24 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 7 / 16 | 9 / 14 | 10 / 14 | 7 / 14 | 4 / 13 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 13 |
Outcome results
Primary
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)
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).
Time frame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the treated set who provided at least 1 PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with available PK data are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TF1 Fed (A) | 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) | 17695 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2a Fed (B) | 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) | 18934 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2a Fasted (C) | 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) | 10645 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2b Fed (D) | 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) | 19356 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2b Fasted (E) | 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) | 12655 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [55.3, 65.5]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [65.6, 78]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [162.8, 194.3]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [139.5, 167.7]
Primary
Maximum Measured Concentration of BI 1358894 in Plasma (Cmax)
Maximum measured concentration of BI 1358894 in plasma (Cmax).
Time frame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the treated set who provided at least 1 PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TF1 Fed (A) | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 497 Nanomole (nmol) / Litre (L) | Standard Error 1.07 |
| TF2a Fed (B) | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 556 Nanomole (nmol) / Litre (L) | Standard Error 1.08 |
| TF2a Fasted (C) | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 484 Nanomole (nmol) / Litre (L) | Standard Error 1.08 |
| TF2b Fed (D) | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 604 Nanomole (nmol) / Litre (L) | Standard Error 1.08 |
| TF2b Fasted (E) | Maximum Measured Concentration of BI 1358894 in Plasma (Cmax) | 909 Nanomole (nmol) / Litre (L) | Standard Error 1.08 |
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [82.3, 115.3]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [154, 217.4]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [96.5, 136.6]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [55.5, 79.5]
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 (AUC0-∞).
Time frame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 240h, 312h after drug administration in each treatment period.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the treated set who provided at least 1 PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with available PK data are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TF1 Fed (A) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 19425 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2a Fed (B) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 20596 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2a Fasted (C) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 11715 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.04 |
| TF2b Fed (D) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 20752 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.05 |
| TF2b Fasted (E) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 13818 Nanomole (nmol)*hours(h)/Litre(L) | Standard Error 1.05 |
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [55.4, 65.7]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [65.2, 77.6]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [160.8, 192.2]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [136.9, 164.7]
Secondary
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)
Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 to 72 hours (AUC0-72).
Time frame: Within 2 hours (h) before and at 10 minutes (min), 20min, 30min, 1h, 1h30min, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration in each treatment period.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all subjects in the treated set who provided at least 1 PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| TF1 Fed (A) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | 11742 Nanomole (nmol) * hours (h) / Litre (L) | Standard Error 1.04 |
| TF2a Fed (B) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | 12297 Nanomole (nmol) * hours (h) / Litre (L) | Standard Error 1.05 |
| TF2a Fasted (C) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | 6635 Nanomole (nmol) * hours (h) / Litre (L) | Standard Error 1.05 |
| TF2b Fed (D) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | 13109 Nanomole (nmol) * hours (h) / Litre (L) | Standard Error 1.05 |
| TF2b Fasted (E) | Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | 8273 Nanomole (nmol) * hours (h) / Litre (L) | Standard Error 1.05 |
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [51.8, 61.7]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [64.4, 77.1]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [169.4, 202.8]
Comparison: Relative bioavailability: ratio of adjusted geometric means was calculated using an analysis of variance (ANOVA). The model on logarithmic scale included random effect of 'subjects within sequences' and fixed effect of 'sequence or block', 'period', 'treatment'.90% CI: [144.3, 173.9]