Healthy
Conditions
Brief summary
Investigation of the relative bioavailability of a single dose of BI 691751 when given alone and together with itraconazole; safety and tolerability
Interventions
DRUGitraconazole
multiple doses of itraconazole given as capsules
DRUGBI 691751
single dose BI 691751 given as 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
1. Healthy male subjects 2. body mass index (BMI) of 18.5 to 29.9 kg/m2 3. Subjects must be able to understand and comply with study requirements
Exclusion criteria
1. Any finding in the medical examination (including blood pressure (BP), pulse rate (PR), or electrocardiogram (ECG)) deviating from normal and judged clinically relevant by the investigator. 2. Pulse rate outside 45 to 100 bpm or repeated measurements of systolic BP outside 90 to 140 mmHg or diastolic BP outside 50 to 90 mmHg. 3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 4. Any alanine transaminase (ALT/GPT), aspartate transaminase (AST/GOT), or gammaglutamyltransferase (GGT) value outside the reference range at the screening examination 5. Any evidence of a concomitant disease judged clinically relevant by the investigator 6. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders 7. Any history of relevant liver diseases such as disturbance of liver function, jaundice, drug induced liver injury, Dubin-Johnson syndrome, Rotor syndrome, or liver tumors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) | from day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h. | AUC0-tz: area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 up to the last quantifiable concentration. |
| Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) | From day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h. | Cmax (maximum measured concentration of BI 691751 in plasma and whole blood). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-infinity (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 Extrapolated to Infinity) | from day 1 to 31 days postdose relative to BI 691751 administration time: -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h. | AUC0-infinity (area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 extrapolated to infinity). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Itraconazole (IT) +BI 691751 / BI 691751 Subjects in treatment sequence of tested drug treatment in period 1, then reference drug treatment in period 2 (T/R): two capsules of 100 mg itraconazole were given twice daily on Day -3 (loading dose) and once daily on Day -2 to Day 7 (10 days of itraconazol treatment in total). In addition, 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 (corresponding to the fourth day of the 10-day itraconazole treatment) in period 1. One tablet of 10 mg BI 691751 was given as a single dose on Day 1 in period 2.
The BI 691751 single dose administrations in the 2 treatment periods were separated by a washout period of at least 7 weeks.
Oral administration with 240 mL water after intake of a standardised meal. | 10 |
| BI 691751 / IT+BI 691751 Subjects in treatment sequence of reference drug treatment in period 1, then tested drug treatment in period 2 (R/T): One tablet of 10 mg BI 691751 was given as a single dose on Day 1 in period 1. Two capsules of 100 mg itraconazole were given twice daily on Day -3 (loading dose) and once daily on Day -2 to Day 7 (10 days of itraconazol treatment in total), and, 1 tablet of 10 mg BI 691751 was given as a single dose on Day 1 (corresponding to the fourth day of the 10-day itraconazole treatment) in period 2.
Oral administration with 240 mL water after intake of a standaridsed meal. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Itraconazole (IT) +BI 691751 / BI 691751 | BI 691751 / IT+BI 691751 | Total |
|---|---|---|---|
| Age, Continuous | 35.1 years STANDARD_DEVIATION 9.9 | 37.4 years STANDARD_DEVIATION 6.6 | 36.3 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration)
AUC0-tz: area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 up to the last quantifiable concentration.
Time frame: from day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.
Population: Pharmacokinetic Set (PKS): included all subjects from the TS who provided at least one primary or secondary pharmacokinetic endpoint in any period that is judged as evaluable for pharmacokinetics and is not affected by protocol violations relevant to the statistical evaluation of bioavailability
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 691751 | AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) | in whole blood | 25000 nmol*h/L | Geometric Coefficient of Variation 25.8 |
| BI 691751 | AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) | in plasma | 2830 nmol*h/L | Geometric Coefficient of Variation 34.6 |
| IT + BI 691751 | AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) | in plasma | 2090 nmol*h/L | Geometric Coefficient of Variation 43.2 |
| IT + BI 691751 | AUC0-tz (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 up to the Last Quantifiable Concentration) | in whole blood | 21600 nmol*h/L | Geometric Coefficient of Variation 25.8 |
Comparison: gMean ratio of IT+BI 691751 to BI 69175 treatment (in plasma)90% CI: [62.371, 87.959]
Comparison: gMean ratio of IT+BI 691751 to BI 691751 treatment (in whole blood)90% CI: [78.04, 95.56]
Primary
Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood)
Cmax (maximum measured concentration of BI 691751 in plasma and whole blood).
Time frame: From day 1 to 31 days postdose relative to BI 691751 administration (h:min): -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.
Population: PKS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 691751 | Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) | in plasma | 157 nmol/L | Geometric Coefficient of Variation 24.4 |
| BI 691751 | Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) | in whole blood | 217 nmol/L | Geometric Coefficient of Variation 16 |
| IT + BI 691751 | Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) | in whole blood | 203 nmol/L | Geometric Coefficient of Variation 21.4 |
| IT + BI 691751 | Cmax (Maximum Measured Concentration of BI 691751 in Plasma and Whole Blood) | in plasma | 150 nmol/L | Geometric Coefficient of Variation 34.1 |
Comparison: gMean ratio of test to reference treatment (in plasma)90% CI: [84.195, 108.537]
Comparison: gMean ratio of test to reference treatment (in whole blood)90% CI: [86.142, 101.57]
Secondary
AUC0-infinity (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 Extrapolated to Infinity)
AUC0-infinity (area under the concentration-time curve of BI 691751 in plasma and whole blood over the time interval from 0 extrapolated to infinity).
Time frame: from day 1 to 31 days postdose relative to BI 691751 administration time: -2:00, 0:10, 0:20, 0:40, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00, 119:00, 143:00, 215:00, 287:00, 383:00, 551:00, 719:00h.
Population: PKS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 691751 | AUC0-infinity (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 Extrapolated to Infinity) | in plasma | 3160 nmol*h/L | Geometric Coefficient of Variation 34.8 |
| BI 691751 | AUC0-infinity (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 Extrapolated to Infinity) | in whole blood | 27700 nmol*h/L | Geometric Coefficient of Variation 29.6 |
| IT + BI 691751 | AUC0-infinity (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 Extrapolated to Infinity) | in plasma | 2360 nmol*h/L | Geometric Coefficient of Variation 43.3 |
| IT + BI 691751 | AUC0-infinity (Area Under the Concentration-time Curve of BI 691751 in Plasma and Whole Blood Over the Time Interval From 0 Extrapolated to Infinity) | in whole blood | 24600 nmol*h/L | Geometric Coefficient of Variation 29.6 |
Comparison: gMean ratio of IT+BI 691751 to BI 691751 treatment (in plasma)90% CI: [62.946, 89.035]
Comparison: gMean ratio of IT+BI 691751 to BI 691751 treatment (in whole blood)90% CI: [78.6, 98.95]