Healthy
Conditions
Brief summary
To investigate the pharmacokinetics of a single oral dose of BI 706321 when given alone or in combination with itraconazole.
Interventions
DRUGBI 706321
Treatment period 1: Single oral dose of 1 film-coated tablet administered with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) Treatment period 2: On day 1 of period 2 (1 h after the itraconazole administration) a single oral dose of 1 film-coated tablet administered with 240 mL of water after an overnight fast of at least 10 h.
DRUGItraconazole
Treatment period 2: Administered as an oral solution formulation once daily for 14 days orally with 240 mL of water after an overnight fast of at least 9 h, starting from day -3 up to day 11 of period 2.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In the first treatment period all subjects are planned to undergo the reference treatment (R), and in the second treatment period all subjects are planned to undergo the test treatment (T).
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 (body temperature, 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 GCP and local legislation
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 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 * During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) (1h for period 2) before and at 0.5h to 190h after BI 706321 administration in each period. Further at 214h to 550h after BI 706321 administration in period 2. | Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
| Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | Within 3 hours (h) (1h for period 2) before and at 0.5h to 190h after BI 706321 administration in each period. Further at 214h to 550h after BI 706321 administration in period 2. | Maximum measured concentration of BI 706321 in plasma (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours (h) (1h for period 2) before and at 0.5h to 190h after BI 706321 administration in each period. Further at 214h to 550h after BI 706321 administration in period 2. | Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
Countries
Germany
Participant flow
Recruitment details
Effect of itraconazole on the pharmacokinetics of a single oral dose of BI 706321 in healthy male subjects (an open-label, two-period fixed sequence design study)
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 706321 (R)/ BI 706321 + Itraconazole (T) On trial day 1 of treatment period 1, a single oral dose of 1 film-coated tablet of 2 milligram (mg) BI 706321 was administered with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) as reference treatment (R).
In treatment period 2: 200 mg itraconazole was administered as an oral solution formulation (concentration: 20 mL of 10 mg/mL) once daily for 14 days orally with 240 mL of water after an overnight fast of at least 9 h, starting from day -3 up to day 11 of period 2. On day 1 of period 2(1 h after the itraconazole administration) a single oral dose of 1 film-coated tablet of 2 mg BI 706321 was administered with 240 mL of water after an overnight fast of at least 10 h (Test Treatment (T)).
There was a washout interval of at least 14 days between the administrations of BI 706321 in the 2 trial periods. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | BI 706321 (R)/ BI 706321 + Itraconazole (T) |
|---|---|
| Age, Continuous | 32.6 Years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 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 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 5 / 14 | 3 / 14 | 5 / 14 | 8 / 14 | 10 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Within 3 hours (h) (1h for period 2) before and at 0.5h to 190h after BI 706321 administration in each period. Further at 214h to 550h after BI 706321 administration in period 2.
Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set who provided at least 1 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 706321 Alone (Reference Treatment (R)) | Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 60.99 Hours * nanomoles / liter |
| BI 706321 + Itraconazole (Test Treatment(T)) | Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 133.45 Hours * nanomoles / liter |
Comparison: The statistical model used for the analysis of the primary PK endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subject' was considered as random, whereas 'treatment' was considered as fixed.90% CI: [194.06, 246.72]
Primary
Maximum Measured Concentration of BI 706321 in Plasma (Cmax)
Maximum measured concentration of BI 706321 in plasma (Cmax).
Time frame: Within 3 hours (h) (1h for period 2) before and at 0.5h to 190h after BI 706321 administration in each period. Further at 214h to 550h after BI 706321 administration in period 2.
Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set who provided at least 1 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 706321 Alone (Reference Treatment (R)) | Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 2.22 nanomoles / liter |
| BI 706321 + Itraconazole (Test Treatment(T)) | Maximum Measured Concentration of BI 706321 in Plasma (Cmax) | 3.47 nanomoles / liter |
Comparison: The statistical model used for the analysis of the primary PK endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subject' was considered as random, whereas 'treatment' was considered as fixed.90% CI: [135.04, 180.89]
Secondary
Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time frame: Within 3 hours (h) (1h for period 2) before and at 0.5h to 190h after BI 706321 administration in each period. Further at 214h to 550h after BI 706321 administration in period 2.
Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set who provided at least 1 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 706321 Alone (Reference Treatment (R)) | Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 50.89 Hours * nanomoles / liter |
| BI 706321 + Itraconazole (Test Treatment(T)) | Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 113.54 Hours * nanomoles / liter |
Comparison: The statistical model used for the analysis of the primary PK endpoints was an analysis of variance (ANOVA) model on the logarithmic scale. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subject' was considered as random, whereas 'treatment' was considered as fixed.90% CI: [198.61, 250.66]