Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of BI 1595043 under fed state (Test, T) and under fasted state (Reference, R).
Interventions
DRUGBI 1595043
Single dose of 30 milligram (mg) BI 1595043 as film coated tablets (1x 5mg tablet and 1x 25mg tablet).
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), body temperature), 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 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, i.e. use of condom (male subjects) plus any of the following methods (female partners): intrauterine device, hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration to the male subject, or barrier method (e.g. diaphragm with spermicide), or surgically sterilised (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy), or postmenopausal, defined as at least 1 year of spontaneous amenorrhea * Sexually abstinent * Vasectomised (vasectomy at least 1 year prior to enrolment) in combination with a barrier method (i.e. condom) Unprotected sexual intercourse (i.e. without use of condom) with a pregnant female partner and sperm donation is not allowed throughout the study and until 30 days after trial completion
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 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 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 * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120, 144 and 168 hours following drug administration. | Area under the concentration-time curve of BI 1595043 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data was logtransformed (natural logarithm) prior to fitting the ANOVA model.This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
| Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | Within 3 hours before drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120, 144 and 168 hours following drug administration. | Maximum measured concentration of BI 1595043 in plasma (Cmax) is reported. The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data was logtransformed (natural logarithm) prior to fitting the ANOVA model.This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours before drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120, 144 and 168 hours following drug administration. | Area under the concentration-time curve of BI 1595043 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data was logtransformed (natural logarithm) prior to fitting the ANOVA model.This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. |
Countries
Belgium
Participant flow
Recruitment details
This was an open-label, randomised, single centre trial using a two-way cross-over design. All subjects received a single oral dose of 30 mg BI 1595043 in film-coated tablet formulation following an overnight fast and after the ingestion of a standardised, high-calorie, high-fat breakfast. Administration sequence was randomly allocated with a wash-out period of at least 8 days between BI 1595043 doses.
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 |
|---|---|
| BI 1595043 Fasted (Reference (R)) / BI 1595043 Fed (Test (T)) Two period crossover separated by a wash-out of at least 8 days:
Period 1: Healthy subjects received a single dose of 30 milligram (mg) BI 1595043 as film coated tablets (1x 5mg tablet and 1x 25mg tablet) following an overnight fast of at least 10 hours.
Period 2: Healthy subjects received a single dose of 30 milligram (mg) BI 1595043 as film coated tablets (1x 5mg tablet and 1x 25mg tablet) following an following a high fat/high calorie breakfast. | 7 |
| BI 1595043 Fed (Test (T)) / BI 1595043 Fasted (Reference (R)) Two period crossover separated by a wash-out of at least 8 days:
Period 1: Healthy subjects received a single dose of 30 milligram (mg) BI 1595043 as film coated tablets (1x 5mg tablet and 1x 25mg tablet) following an following a high fat/high calorie breakfast.
Period 2: Healthy subjects received a single dose of 30 milligram (mg) BI 1595043 as film coated tablets (1x 5mg tablet and 1x 25mg tablet) following an overnight fast of at least 10 hours. | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | BI 1595043 Fed (Test (T)) / BI 1595043 Fasted (Reference (R)) | Total | BI 1595043 Fasted (Reference (R)) / BI 1595043 Fed (Test (T)) |
|---|---|---|---|
| Age, Continuous | 38.2 years STANDARD_DEVIATION 5.8 | 35.5 years STANDARD_DEVIATION 7.2 | 33.3 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 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 | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 1 / 13 | 2 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 1595043 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data was logtransformed (natural logarithm) prior to fitting the ANOVA model.This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Time frame: Within 3 hours before drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120, 144 and 168 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were randomised and received at least one dose of trial medication and who provided at least one pharmacokinetic (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) |
|---|---|---|
| BI 1595043 Under Fasted Condition (Reference (R)) | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | NA hour*nanomol/Liter |
| BI 1595043 Under Fed Condition (T (Test)) | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | NA hour*nanomol/Liter |
Comparison: Relative bioavailability of BI 1595043 administered in fed state (Test) compared with BI 1595043 administered in fasted state (Reference) was estimated by the ratios of the gMeans (Test/Reference). Their corresponding 2-sided 90% CIs were provided. This method corresponds to 2 one-sided t-test procedures, each at the 5% significance level.90% CI: [99.34, 106.29]
Primary
Maximum Measured Concentration of BI 1595043 in Plasma (Cmax)
Maximum measured concentration of BI 1595043 in plasma (Cmax) is reported. The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data was logtransformed (natural logarithm) prior to fitting the ANOVA model.This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Time frame: Within 3 hours before drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120, 144 and 168 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were randomised and received at least one dose of trial medication and who provided at least one pharmacokinetic (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) |
|---|---|---|
| BI 1595043 Under Fasted Condition (Reference (R)) | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | NA nanomol/Liter |
| BI 1595043 Under Fed Condition (T (Test)) | Maximum Measured Concentration of BI 1595043 in Plasma (Cmax) | NA nanomol/Liter |
Comparison: Relative bioavailability of BI 1595043 administered in fed state (Test) compared with BI 1595043 administered in fasted state (Reference) was estimated by the ratios of the gMeans (Test/Reference). Their corresponding 2-sided 90% CIs were provided. This method corresponds to 2 one-sided t-test procedures, each at the 5% significance level.90% CI: [69.77, 86.76]
Secondary
Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 1595043 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. Data was logtransformed (natural logarithm) prior to fitting the ANOVA model.This model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Time frame: Within 3 hours before drug administration and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120, 144 and 168 hours following drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): all subjects who were randomised and received at least one dose of trial medication and who provided at least one pharmacokinetic (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) |
|---|---|---|
| BI 1595043 Under Fasted Condition (Reference (R)) | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA hour*nanomol/Liter |
| BI 1595043 Under Fed Condition (T (Test)) | Area Under the Concentration-time Curve of BI 1595043 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA hour*nanomol/Liter |
Comparison: Relative bioavailability of BI 1595043 administered in fed state (Test) compared with BI 1595043 administered in fasted state (Reference) was estimated by the ratios of the gMeans (Test/Reference). Their corresponding 2-sided 90% CIs were provided. This method corresponds to 2 one-sided t-test procedures, each at the 5% significance level.90% CI: [99.73, 106.89]