Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of BI 1358894 in healthy male subjects following oral administration of single rising doses. Secondary objectives are the exploration of the pharmacokinetics (PK), including dose proportionality of BI 1358894 after single dosing.
Interventions
DRUGPlacebo
Tablet
DRUGBI 1358894
Tablet
DRUGBI 1358894 (Test)
Fasting state
DRUGBI 1358894 (Reference)
Fed state
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 according to the investigator's assessment, 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 45 years (incl.) * BMI of 18.5 to 29.9 kg/m2 (incl.) * Signed and dated written informed consent prior to admission to the study in accordance with 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 one month after the last administration of trial medication. Adequate methods are: * Sexual abstinence or * A vasectomy performed at least 1 year prior to screening in combination with a barrier method (condom) or * Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subjects female partner or * The use of condoms, if the female partner uses in addition an adequate contraception method, 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 one month after the last administration of trial medication
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) is deviating from normal * 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 \> ULN, erythrocyte sedimentation rate (ESR) ≥ 15 millimeters/hour, liver and kidney parameter above ULN, other laboratory values outside the reference range 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 * Cholecystectomy and/or 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 prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation) * Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug * 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 as per investigator judgment or positive drug screening * Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial * Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial * Inability to comply with dietary regimen of trial site * A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant ECG finding at screening * A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not 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 Event | From start of treatment until end of trial. Up to 14 days for single rising dose part under fasting condition (3mg to 200mg) and the food effect part and up to 33 days for the single rising dose part under fed conditions (200mg fed dose group) | Percentage of subjects with drug-related adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | Within 2 hours (h) before and 0.167h, 0.333h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h after drug administration | Area under the concentration-time curve of the analyte BI1358894 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) |
| Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | Within 2 hours (h) before and 0.167h, 0.333h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h after drug administration | Area under the concentration-time curve of the analyte BI1358894 in plasma over the time interval from 0 to the last quantifiable data time point (AUC0-tz). |
| Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | Within 2 hours (h) before and 0.167h, 0.333h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h after drug administration | Maximum measured concentration of the analyte BI 1358894 in plasma (Cmax). |
Countries
Germany
Participant flow
Recruitment details
Single rising oral doses of BI 1358894 in healthy male subjects (single-blind, partially randomised, placebo-controlled parallel group design) and effect of food on the relative bioavailability of BI 1358894 (open-label, randomised, two-way cross-over)
Pre-assignment details
All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they met all implemented inclusion/exclusion criteria, Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated
Participants by arm
| Arm | Count |
|---|---|
| Placebo matching placebo Single Rising Dose (SRD) part | 15 |
| BI 3mg oral administration of BI 1358894 film-coated tablet (3\*1 milligram (mg) tablet) Single Rising Dose (SRD) part | 6 |
| BI 6mg oral administration of BI 1358894 film-coated tablet (6\*1mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 10mg oral administration of BI 1358894 film-coated tablet (2\*5mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 25mg oral administration of BI 1358894 film-coated tablet (1\*25mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 50mg oral administration of BI 1358894 film-coated tablet (2\*25mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 100mg oral administration of BI 1358894 film-coated tablet (1\*100mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 200mg Fast oral administration of BI 1358894 film-coated tablet in fasting status (2\*100mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 200mg Fed oral administration of BI 1358894 film-coated tablet in fed status (2\*100mg tablet) Single Rising Dose (SRD) part | 6 |
| BI 50mg Fed / BI 50mg Fast oral administration of BI 1358894 film-coated tablet in fed state (Test) (2\*25mg)/ oral administration of BI 1358894 film-coated tablet in fasting state (Reference) (2\*25mg) Food effect (FE) part | 4 |
| BI 50mg Fast / BI 50m Fed oral administration of BI 1358894 film-coated tablet in fasting state (Reference) (2\*25mg) / oral administration of BI 1358894 film-coated tablet in fed state (Test) (2\*25mg) Food effect (FE) part | 4 |
| BI 100mg Fed / BI 100mg Fast oral administration of BI 1358894 film-coated tablet in fed state (Test) (1\*100mg)/ oral administration of BI 1358894 film-coated tablet in fasting state (Reference) (1\*100mg) Food effect (FE) part | 6 |
| BI 100mg Fast / BI 100m Fed oral administration of BI 1358894 film-coated tablet in fasting state (Reference) (1\*100mg)/ oral administration of BI 1358894 film-coated tablet in fed state (Test) (1\*100mg) Food effect (FE) part | 6 |
| Total | 83 |
Baseline characteristics
| Characteristic | BI 100mg Fast / BI 100m Fed | Total | Placebo | BI 50mg Fed / BI 50mg Fast | BI 200mg Fed | BI 200mg Fast | BI 100mg | BI 50mg | BI 25mg | BI 10mg | BI 6mg | BI 3mg | BI 50mg Fast / BI 50m Fed | BI 100mg Fed / BI 100mg Fast |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.0 Years STANDARD_DEVIATION 8.1 | 34.9 Years STANDARD_DEVIATION 7.2 | 33.7 Years STANDARD_DEVIATION 5.8 | 36.8 Years STANDARD_DEVIATION 8.8 | 28.0 Years STANDARD_DEVIATION 3.6 | 38.3 Years STANDARD_DEVIATION 7 | 35.5 Years STANDARD_DEVIATION 6.6 | 40.2 Years STANDARD_DEVIATION 3.5 | 36.2 Years STANDARD_DEVIATION 7.3 | 36.2 Years STANDARD_DEVIATION 6 | 33.7 Years STANDARD_DEVIATION 7.4 | 40.2 Years STANDARD_DEVIATION 7.4 | 32.5 Years STANDARD_DEVIATION 8.3 | 34.2 Years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 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 | 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 | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 80 Participants | 15 Participants | 4 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 6 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 | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 83 Participants | 15 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 6 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 48 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 3 / 15 | 3 / 6 | 6 / 6 | 0 / 6 | 2 / 6 | 4 / 6 | 4 / 6 | 3 / 6 | 6 / 6 | 28 / 48 | 7 / 8 | 7 / 8 | 6 / 12 | 8 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 48 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percentage of Subjects With Drug- Related Adverse Event
Percentage of subjects with drug-related adverse events
Time frame: From start of treatment until end of trial. Up to 14 days for single rising dose part under fasting condition (3mg to 200mg) and the food effect part and up to 33 days for the single rising dose part under fed conditions (200mg fed dose group)
Population: Treated Set (TS): This subject set included all subjects who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug- Related Adverse Event | 0.0 Percentage |
| BI 3mg | Percentage of Subjects With Drug- Related Adverse Event | 16.7 Percentage |
| BI 6mg | Percentage of Subjects With Drug- Related Adverse Event | 50.0 Percentage |
| BI 10mg | Percentage of Subjects With Drug- Related Adverse Event | 0.0 Percentage |
| BI 25mg | Percentage of Subjects With Drug- Related Adverse Event | 33.3 Percentage |
| BI 50mg | Percentage of Subjects With Drug- Related Adverse Event | 66.7 Percentage |
| BI 100mg | Percentage of Subjects With Drug- Related Adverse Event | 66.7 Percentage |
| BI 200mg Fast | Percentage of Subjects With Drug- Related Adverse Event | 50.0 Percentage |
| BI 200mg Fed | Percentage of Subjects With Drug- Related Adverse Event | 66.7 Percentage |
| BI 50mg Fed | Percentage of Subjects With Drug- Related Adverse Event | 87.5 Percentage |
| BI 50mg Fast | Percentage of Subjects With Drug- Related Adverse Event | 87.5 Percentage |
| BI 100mg Fed | Percentage of Subjects With Drug- Related Adverse Event | 50.0 Percentage |
| BI 100mg Fast | Percentage of Subjects With Drug- Related Adverse Event | 66.7 Percentage |
Secondary
Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity
Area under the concentration-time curve of the analyte BI1358894 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Time frame: Within 2 hours (h) before and 0.167h, 0.333h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h after drug administration
Population: Pharmacokinetic parameter analysis set (PKS):~The PK parameter analysis set (PKS) included all subjects from the TS receiving BI 1358894 who provided at least 1 secondary PK parameter (AUC or Cmax) that was not excluded because of protocol deviations relevant to the statistical evaluation of PK endpoints
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 341 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 20.7 |
| BI 3mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 596 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 33.3 |
| BI 6mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 922 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 20.4 |
| BI 10mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 2540 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 29.9 |
| BI 25mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 4470 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 25.5 |
| BI 50mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 2960 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 1570 |
| BI 100mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 13700 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 45.7 |
| BI 200mg Fast | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 33800 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 30.1 |
| BI 200mg Fed | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 4920 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 27.1 |
| BI 50mg Fed | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 7660 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 41 |
| BI 50mg Fast | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 7020 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 56.4 |
| BI 100mg Fed | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | 16900 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 21.5 |
Comparison: The statistical model to assess relative bioavailability in the FE part was an analysis of variance (ANOVA) on the ln-transformed parameters AUC and Cmax including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'90% CI: [130.66, 185.3]
Comparison: The statistical model to assess relative bioavailability in the FE part was an analysis of variance (ANOVA) on the ln-transformed parameters AUC and Cmax including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'90% CI: [196.25, 293.81]
Secondary
Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point
Area under the concentration-time curve of the analyte BI1358894 in plasma over the time interval from 0 to the last quantifiable data time point (AUC0-tz).
Time frame: Within 2 hours (h) before and 0.167h, 0.333h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h after drug administration
Population: Pharmacokinetic parameter analysis set (PKS):~The PK parameter analysis set (PKS) included all subjects from the TS receiving BI 1358894 who provided at least 1 secondary PK parameter (AUC or Cmax) that was not excluded because of protocol deviations relevant to the statistical evaluation of PK endpoints
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 288 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 18.5 |
| BI 3mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 569 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 32.7 |
| BI 6mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 861 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 17.7 |
| BI 10mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 2380 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 29.7 |
| BI 25mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 4170 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 26.2 |
| BI 50mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 2520 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 2670 |
| BI 100mg | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 12600 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 42 |
| BI 200mg Fast | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 32800 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 29 |
| BI 200mg Fed | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 4440 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 23.5 |
| BI 50mg Fed | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 6940 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 36.2 |
| BI 50mg Fast | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 6320 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 53.4 |
| BI 100mg Fed | Area Under the Concentration-time Curve of the Analyte BI1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Time Point | 15500 Nanomoles*Hour per Litre | Geometric Coefficient of Variation 19.3 |
Comparison: The statistical model to assess relative bioavailability in the FE part was an analysis of variance (ANOVA) on the ln-transformed parameters AUC and Cmax including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'90% CI: [132.73, 184.22]
Comparison: The statistical model to assess relative bioavailability in the FE part was an analysis of variance (ANOVA) on the ln-transformed parameters AUC and Cmax including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'90% CI: [200.7, 300.44]
Secondary
Maximum Measured Concentration of the Analyte BI 1358894 in Plasma
Maximum measured concentration of the analyte BI 1358894 in plasma (Cmax).
Time frame: Within 2 hours (h) before and 0.167h, 0.333h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 192h after drug administration
Population: Pharmacokinetic parameter analysis set (PKS):~The PK parameter analysis set (PKS) included all subjects from the TS receiving BI 1358894 who provided at least 1 secondary PK parameter (AUC or Cmax) that was not excluded because of protocol deviations relevant to the statistical evaluation of PK endpoints
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 27.6 Nanomoles per Litre | Geometric Coefficient of Variation 30 |
| BI 3mg | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 35.9 Nanomoles per Litre | Geometric Coefficient of Variation 33.8 |
| BI 6mg | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 59.7 Nanomoles per Litre | Geometric Coefficient of Variation 13.4 |
| BI 10mg | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 84.2 Nanomoles per Litre | Geometric Coefficient of Variation 44.2 |
| BI 25mg | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 183 Nanomoles per Litre | Geometric Coefficient of Variation 56.3 |
| BI 50mg | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 94.3 Nanomoles per Litre | Geometric Coefficient of Variation 735 |
| BI 100mg | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 385 Nanomoles per Litre | Geometric Coefficient of Variation 26.8 |
| BI 200mg Fast | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 857 Nanomoles per Litre | Geometric Coefficient of Variation 22.2 |
| BI 200mg Fed | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 149 Nanomoles per Litre | Geometric Coefficient of Variation 59.4 |
| BI 50mg Fed | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 237 Nanomoles per Litre | Geometric Coefficient of Variation 24.9 |
| BI 50mg Fast | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 210 Nanomoles per Litre | Geometric Coefficient of Variation 38.8 |
| BI 100mg Fed | Maximum Measured Concentration of the Analyte BI 1358894 in Plasma | 517 Nanomoles per Litre | Geometric Coefficient of Variation 8.61 |
Comparison: The statistical model to assess relative bioavailability in the FE part was an analysis of variance (ANOVA) on the ln-transformed parameters AUC and Cmax including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'90% CI: [114.25, 220.56]
Comparison: The statistical model to assess relative bioavailability in the FE part was an analysis of variance (ANOVA) on the ln-transformed parameters AUC and Cmax including effects for 'sequence', 'subjects nested within sequences', 'period', and 'treatment'90% CI: [203.37, 297.89]