Healthy
Conditions
Brief summary
This first-in man trial is designed to investigate the safety and tolerability of BI 894416 in healthy male subjects following oral administration of single rising doses. Pharmacokinetics (PK) including dose proportionality after single dosing of BI 894416 as oral solution will be explored, the investigation of PK of BI 894416 as tablet formulation and the exploration of relative bioavailability of BI 894416 as tablet formulation compared to oral solution.
Interventions
DRUGBI 894416
powder for oral solution
DRUGPlacebo
Oral solution
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 subjects according to the assessment of the investigator, 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 45 years (incl.) * Body Mass Index (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 Good Clinical Practice (GCP) and local legislation
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG) and including the neurological examination) is deviating from normal and judged 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 beats per minute (bpm) * Any laboratory value outside the reference range that 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 than 30 g per day) * Drug abuse 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) 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 In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events in SRD Part | From drug administration until end of the trial, up to 17 days. | Percentage of participants with drug-related adverse events (AEs) in SRD part. Percentages are calculated using total number of subjects per treatment as the denominator. Percentages were rounded up to 1 decimal places. |
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-inf) in SRD Part | Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 168 h after drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) in SRD part is presented. |
| Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 168 h after drug administration. | Maximum measured concentration of BI 894416 in plasma (Cmax) in SRD part is presented. |
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) in Rel BA Part | Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in rel BA part is presented. BI 894416 40 mg tb arm was compared in a descriptive fashion with other dose groups without statistical analysis. |
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in Rel BA Part | Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) in rel BA part is presented. BI 894416 40 mg tb arm was compared in a descriptive fashion with other dose groups without statistical analysis. |
| Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in Rel BA Part | Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration. | Maximum measured concentration of BI 894416 in plasma (Cmax) in rel BA part is presented. BI 894416 40 mg tb arm was compared in a descriptive fashion with other dose groups without statistical analysis. |
Countries
Germany
Participant flow
Recruitment details
Single rising dose (SRD) part was designed as single-blind, partially randomized within dose groups, placebo-controlled, parallel-group design and relative bioavailability (rel BA) part was an open-label, randomized two-way crossover followed by a fixed sequence design in healthy volunteers.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialized site which would ensure that all participants met all inclusion/exclusion criteria. Participants were not to be entered/randomised to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching BI 894416 (SRD Part) Participants were orally administered single dose of placebo solution matching to BI 894416 with 240 mL of water after an overnight fast of at least 10 hours (h) in SRD Part. | 14 |
| BI 894416 3 Milligram (mg) (SRD Part) Participants were administered single dose of BI 894416 3 milligram (mg) powder for oral solution (PfOS) with 240 mL of water after an overnight fast of at least 10 hours (h) in SRD Part. | 6 |
| BI 894416 10 mg (SRD Part) Participants were administered single dose of BI 894416 10 mg powder for oral solution with 240 mL of water after an overnight fast of at least 10 h in SRD Part. | 6 |
| BI 894416 20 mg (SRD Part) Participants were administered single dose of BI 894416 20 mg powder for oral solution with 240 mL of water after an overnight fast of at least 10 h in SRD Part. | 6 |
| BI 894416 30 mg (SRD Part) Participants were administered single dose of BI 894416 30 mg powder for oral solution with 240 mL of water after an overnight fast of at least 10 h in SRD Part. | 6 |
| BI 894416 40 mg (SRD Part) Participants were administered single dose of BI 894416 40 mg powder for oral solution with 240 mL of water after an overnight fast of at least 10 h in SRD Part. | 6 |
| BI 894416 54 mg (SRD Part) Participants were administered single dose of BI 894416 54 mg powder for oral solution with 240 mL of water after an overnight fast of at least 10 h in SRD Part. | 6 |
| BI 894416 70 mg (SRD Part) Participants were administered single dose of BI 894416 70 mg powder for oral solution with 240 mL of water after an overnight fast of at least 10 h in SRD Part. | 6 |
| BI 894416 10mg tb / 10mg PfOS / 40mg tb Participants were administered single dose of BI 894416 10 mg tablet (tb) in period 1 followed by BI 894416 10 mg powder for oral solution in period 2 followed by BI 894416 4\*10 mg tablets in period 3. Dosages for all periods were administered with 240 mL of water after an overnight fast of at least 10 h. Treatments in period 1 and 2 were separated by a wash-out period of at least 6 days and treatments in periods 2 and 3 were separated by a wash-out period of at least 10 days, in rel BA Part. | 6 |
| BI 894416 10mg PfOS / 10mg tb / 40mg tb Participants were administered single dose of BI 894416 10 mg powder for oral solution in period 1 followed by BI 894416 10 mg tablet (tb) in period 2 followed by BI 894416 4\*10 mg tablets in period 3. Dosages for all periods were administered with 240 mL of water after an overnight fast of at least 10 h. Treatments in period 1 and 2 were separated by a wash-out period of at least 6 days and treatments in periods 2 and 3 were separated by a wash-out period of at least 10 days, in rel BA Part. | 6 |
| Total | 68 |
Baseline characteristics
| Characteristic | Placebo Matching BI 894416 (SRD Part) | BI 894416 3 Milligram (mg) (SRD Part) | BI 894416 10 mg (SRD Part) | BI 894416 20 mg (SRD Part) | BI 894416 30 mg (SRD Part) | BI 894416 40 mg (SRD Part) | BI 894416 54 mg (SRD Part) | BI 894416 70 mg (SRD Part) | BI 894416 10mg tb / 10mg PfOS / 40mg tb | BI 894416 10mg PfOS / 10mg tb / 40mg tb | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.8 Years STANDARD_DEVIATION 7.3 | 33.2 Years STANDARD_DEVIATION 7.3 | 33.5 Years STANDARD_DEVIATION 6.4 | 35.7 Years STANDARD_DEVIATION 7.1 | 33.7 Years STANDARD_DEVIATION 7 | 38.2 Years STANDARD_DEVIATION 6.3 | 34.3 Years STANDARD_DEVIATION 5.5 | 34.2 Years STANDARD_DEVIATION 9.1 | 31.7 Years STANDARD_DEVIATION 8.3 | 30.5 Years STANDARD_DEVIATION 6.9 | 33.9 Years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 66 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 |
| 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 |
| 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 |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 |
| 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 |
| 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 |
| Race (NIH/OMB) White | 14 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 67 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 |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 68 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 3 / 14 | 2 / 6 | 2 / 6 | 5 / 6 | 2 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 4 / 12 | 3 / 12 | 4 / 12 |
| serious Total, serious adverse events | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events in SRD Part
Percentage of participants with drug-related adverse events (AEs) in SRD part. Percentages are calculated using total number of subjects per treatment as the denominator. Percentages were rounded up to 1 decimal places.
Time frame: From drug administration until end of the trial, up to 17 days.
Population: Treated set (TS): This subject set included all subjects who received at least 1 dose of BI 894416 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 894416 (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 0.0 Percentage of participants |
| BI 894416 3 Milligram (mg) (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 0.0 Percentage of participants |
| BI 894416 10 mg (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 0.0 Percentage of participants |
| BI 894416 20 mg (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 33.3 Percentage of participants |
| BI 894416 30 mg (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 16.7 Percentage of participants |
| BI 894416 40 mg (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 0.0 Percentage of participants |
| BI 894416 54 mg (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 16.7 Percentage of participants |
| BI 894416 70 mg (SRD Part) | Percentage of Participants With Drug-related Adverse Events in SRD Part | 16.7 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-inf) in Rel BA Part
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) in rel BA part is presented. BI 894416 40 mg tb arm was compared in a descriptive fashion with other dose groups without statistical analysis.
Time frame: Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects of the treated set who provided at least 1 PK parameter that was not excluded because of an important protocol deviation relevant to the statistical evaluation of PK endpoints or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 894416 (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in Rel BA Part | 975 nanomole (nmol) * hour (h)/Litre (L) | Geometric Coefficient of Variation 97.5 |
| BI 894416 3 Milligram (mg) (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in Rel BA Part | 879 nanomole (nmol) * hour (h)/Litre (L) | Geometric Coefficient of Variation 90.4 |
| BI 894416 10 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in Rel BA Part | 6060 nanomole (nmol) * hour (h)/Litre (L) | Geometric Coefficient of Variation 63.5 |
Comparison: The analysis of variance (ANOVA) model on the logarithmic scale including 'sequence', 'period', and 'treatment' as fixed effects and 'subject within sequence' as random effect. No hypothesis was tested and no acceptance range was specified. This was an intra-individual assessment and actually only 12 subjects were analyzed.90% CI: [101.2, 121.38]
Secondary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) in SRD part is presented.
Time frame: Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 168 h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects of the treated set who provided at least 1 PK parameter that was not excluded because of an important protocol deviation relevant to the statistical evaluation of PK endpoints or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 894416 (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 345 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 34.9 |
| BI 894416 3 Milligram (mg) (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 640 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 101 |
| BI 894416 10 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 1470 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 96.7 |
| BI 894416 20 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 3270 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 27.1 |
| BI 894416 30 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 6020 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 20.6 |
| BI 894416 40 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 7210 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 28.1 |
| BI 894416 54 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) in SRD Part | 11400 nanomole (nmol) * hour (h) / Litre (L) | Geometric Coefficient of Variation 29.6 |
Secondary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) in Rel BA Part
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in rel BA part is presented. BI 894416 40 mg tb arm was compared in a descriptive fashion with other dose groups without statistical analysis.
Time frame: Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects of the treated set who provided at least 1 PK parameter that was not excluded because of an important protocol deviation relevant to the statistical evaluation of PK endpoints or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 894416 (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) in Rel BA Part | 941 nanomole (nmol) * hour (h)/Litre (L) | Geometric Coefficient of Variation 95.2 |
| BI 894416 3 Milligram (mg) (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) in Rel BA Part | 853 nanomole (nmol) * hour (h)/Litre (L) | Geometric Coefficient of Variation 89 |
| BI 894416 10 mg (SRD Part) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) in Rel BA Part | 5870 nanomole (nmol) * hour (h)/Litre (L) | Geometric Coefficient of Variation 61.2 |
Comparison: The analysis of variance (ANOVA) model on the logarithmic scale including 'sequence', 'period', and 'treatment' as fixed effects and 'subject within sequence' as random effect. No hypothesis was tested and no acceptance range was specified. This was an intra-individual assessment and actually 12 subjects were analyzed90% CI: [100.73, 120.79]
Secondary
Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in Rel BA Part
Maximum measured concentration of BI 894416 in plasma (Cmax) in rel BA part is presented. BI 894416 40 mg tb arm was compared in a descriptive fashion with other dose groups without statistical analysis.
Time frame: Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects of the treated set who provided at least 1 PK parameter that was not excluded because of an important protocol deviation relevant to the statistical evaluation of PK endpoints or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 894416 (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in Rel BA Part | 199 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 39.5 |
| BI 894416 3 Milligram (mg) (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in Rel BA Part | 180 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 53.4 |
| BI 894416 10 mg (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in Rel BA Part | 1160 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 39.2 |
Comparison: The analysis of variance (ANOVA) model on the logarithmic scale including 'sequence', 'period', and 'treatment' as fixed effects and 'subject within sequence' as random effect. No hypothesis was tested and no acceptance range was specified. This was an intra-individual assessment and actually only 12 subjects were analyzed.90% CI: [89.74, 135.96]
Secondary
Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part
Maximum measured concentration of BI 894416 in plasma (Cmax) in SRD part is presented.
Time frame: Pharmacokinetic samples were collected at 2 hours (h) prior drug administration and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 96, 168 h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects of the treated set who provided at least 1 PK parameter that was not excluded because of an important protocol deviation relevant to the statistical evaluation of PK endpoints or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 894416 (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 55.4 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 11.1 |
| BI 894416 3 Milligram (mg) (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 161.0 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 37.5 |
| BI 894416 10 mg (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 352.0 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 26.9 |
| BI 894416 20 mg (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 527.0 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 31.3 |
| BI 894416 30 mg (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 1170.0 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 26.4 |
| BI 894416 40 mg (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 1240.0 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 23 |
| BI 894416 54 mg (SRD Part) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) in SRD Part | 2130.0 nanomole (nmol)/Litre (L) | Geometric Coefficient of Variation 16.7 |