Healthy
Conditions
Brief summary
Investigate the relative bioavailability of BI 894416 as tablet formulation following a high-fat, high calorie breakfast (Test, T) compared with administration in the fasting state (Reference, R)
Interventions
DRUGBI 894416
3 tablets with 10 milligram (mg) of BI 894416 (total: 30 mg) were administered as one single oral dose with 240 milliliter (mL) of water.
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) * 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
Exclusion criteria
* Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG) and including the neurological examination) 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 45 to 90 bpm * 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 * 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 (unless the subject quit smoking for at least 3 months prior to first planned administration of trial medication) * Alcohol abuse (consumption of more than 24 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 Electrocardiogram (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 In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Within 3 hours before and then 15 minutes (min), 30 min, 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34 and 48 hours 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). Time points of pharmacokinetic (PK) blood samples are given as planned time relative to start of drug administration. |
| Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | Within 3 hours before and then 15 minutes (min), 30 min, 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34 and 48 hours after drug administration. | Maximum measured concentration of BI 894416 in plasma (Cmax). Time points of pharmacokinetic (PK) blood samples are given as planned time relative to start of drug administration. |
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-∞ ) | Within 3 hours before and then 15 minutes (min), 30 min, 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34 and 48 hours after drug administration. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞ ). Time points of pharmacokinetic (PK) blood samples are given as planned time relative to start of drug administration. |
Countries
Germany
Participant flow
Recruitment details
A randomised, open-label, two-sequence crossover, single-dose, two-period trial in healthy male subjects to compare the test treatment (T) to the reference treatment (R). The treatments were 2 single oral doses of BI 894416 , administered under fasted (R) and fed (T) conditions and separated by a wash-out period of at least 5 days.
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 |
|---|---|
| 30 mg of BI 894416 Fasted - 30 mg of BI 894416 Fed 3 tablets with 10 milligram (mg) of BI 894416 (total: 30 mg) were administered as one single oral dose with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (fasted conditions) as reference treatment (R) followed by a wash-out period of at least 5 days followed by 3 tablets with 10 mg of BI 894416 (total: 30 mg) administered as a single oral dose with 240 mL of water 30 minutes after a high-fat, high-calorie meal (fed conditions) as test treatment (T). | 7 |
| 30 mg of BI 894416 Fed - 30 mg of BI 894416 Fasted 3 tablets with 10 milligram (mg) of BI 894416 (total: 30 mg) were administered as one single oral dose with 240 milliliter (mL) of water after a high-fat, high-calorie meal (fed conditions) as test treatment (T) followed by a wash-out period of at least 5 days followed by 3 tablets with 10 mg of BI 894416 (total: 30 mg) administered as a single oral dose with 240 mL of water 30 minutes after an overnight fast of at least 10 hours (fasted conditions) as reference treatment (R). | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | 30 mg of BI 894416 Fed - 30 mg of BI 894416 Fasted | Total | 30 mg of BI 894416 Fasted - 30 mg of BI 894416 Fed |
|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 8.7 | 36.4 years STANDARD_DEVIATION 8.6 | 31.4 years STANDARD_DEVIATION 5.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 1 / 14 | 3 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
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)
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). Time points of pharmacokinetic (PK) blood samples are given as planned time relative to start of drug administration.
Time frame: Within 3 hours before and then 15 minutes (min), 30 min, 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34 and 48 hours after drug administration.
Population: The pharmacokinetic set included all subjects who received at least one dose of trial medication and provided at least one PK endpoint that was defined as primary and that was not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 894416 30 mg Fed (T) | 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) | 4436.69 nanomole (nmol) * hour (h) / liter (L) |
| BI 894416 30 mg Fast (R) | 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) | 4458.63 nanomole (nmol) * hour (h) / liter (L) |
Comparison: Exploratory trial, no formal hypotheses were tested. Analysis of Variance (ANOVA) model on the logarithmic scale was used which included effects accounting for sources of variation: 'sequence' (fixed effect), 'subjects within sequences' (random effect), 'period' (fixed effect) and 'treatment' (fixed effect).90% CI: [95.36, 103.83]
Primary
Maximum Measured Concentration of BI 894416 in Plasma (Cmax)
Maximum measured concentration of BI 894416 in plasma (Cmax). Time points of pharmacokinetic (PK) blood samples are given as planned time relative to start of drug administration.
Time frame: Within 3 hours before and then 15 minutes (min), 30 min, 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34 and 48 hours after drug administration.
Population: The pharmacokinetic set included all subjects who received at least one dose of trial medication and provided at least one PK endpoint that was defined as primary and that was not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 894416 30 mg Fed (T) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | 492.90 nanomole (nmol) / liter (L) |
| BI 894416 30 mg Fast (R) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | 703.05 nanomole (nmol) / liter (L) |
Comparison: Exploratory trial, no formal hypotheses were tested. Analysis of Variance (ANOVA) model on the logarithmic scale was used which included effects accounting for sources of variation: 'sequence' (fixed effect), 'subjects within sequences' (random effect), 'period' (fixed effect) and 'treatment' (fixed effect).90% CI: [62.67, 78.44]
Secondary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ )
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞ ). Time points of pharmacokinetic (PK) blood samples are given as planned time relative to start of drug administration.
Time frame: Within 3 hours before and then 15 minutes (min), 30 min, 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 34 and 48 hours after drug administration.
Population: The pharmacokinetic set included all subjects who received at least one dose of trial medication and provided at least one PK endpoint that was defined as primary and that was not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 894416 30 mg Fed (T) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ ) | 4463.26 nanomole (nmol) * hour (h) / liter (L) |
| BI 894416 30 mg Fast (R) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ ) | 4472.94 nanomole (nmol) * hour (h) / liter (L) |
Comparison: Exploratory trial, no formal hypotheses were tested. Analysis of Variance (ANOVA) model on the logarithmic scale was used which included effects accounting for sources of variation: 'sequence' (fixed effect), 'subjects within sequences' (random effect), 'period' (fixed effect) and 'treatment' (fixed effect).90% CI: [95.64, 104.11]