Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate whether and to what extent co-administration of multiple doses of itraconazole affect single dose pharmacokinetics of BI1015550, i.e. to compare the relative bioavailability of 6 mg BI 1015550 when given alone (reference, treatment R) to the relative bioavailability of 6 mg of BI 1015550 given on the 4th day of a 12-day-treatment with itraconazole (test, treatment T) following oral administration in healthy male subjects.
Interventions
DRUGBI 1015550
single dose of BI 1015550 6 milligram (mg) tablet orally with 240 milliLitre (mL) of water after an overnight fast of at least 10 hours
DRUGitraconazole
200 mg itraconazole solution given orally once daily with 240 mL of water after an overnight fast of at least 9 h
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 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 (BP (Blood Pressure), PR (Pulse Rate)), 12-lead ECG (Electrocardiogram), and clinical laboratory tests * Age of 18 to 55 years (incl.) * 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 GCP and local legislation
Exclusion criteria
* Any finding in the medical examination (including BP (Blood Pressure), PR (Pulse Rate) or ECG (Electrocardiogram)) 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 45 to 90 bpm (beats per minute) * 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, including but not limited to mood disorders and any history of suicidality. * 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 or other Azoles ) * 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 * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to 119 Hours | Up to 215 hours (Please check measure description for detailed timeframe) | Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 to 119 hours (h) (AUC0-119). Standard error is actually geometric standard error. Geometric mean (gMean) is actually adjusted geometric mean. Pharmacokinetic samples were collected at 3:00 hours:minutes (h:m) prior to drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00 and 119:00 h:m after drug administration during Visit 2 and Visit 3. Additionally at 143:00, 167:00, 191:00 and 215:00 h:m after drug administration during Visit 3. |
| Maximum Measured Concentration of the BI 1015550 in Plasma | Up to 215 hours (Please check measure description for detailed timeframe) | Maximum measured concentration of the BI 1015550 in plasma (Cmax). Standard error is actually geometric standard error. Geometric mean is actually adjusted geometric mean. Pharmacokinetic samples were collected at 3:00 h:m prior to drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00 and 119:00 h:m after drug administration during Visit 2 and Visit 3. Additionally at 143:00, 167:00, 191:00 and 215:00 h:m after drug administration during Visit 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Up to 215 hours (Please check measure description for detailed timeframe) | Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). Standard error is actually geometric standard error. Geometric mean is actually adjusted geometric mean. Pharmacokinetic samples were collected at 3:00 h:m prior to drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00 and 119:00 h:m after drug administration during Visit 2 and Visit 3. Additionally at 143:00, 167:00, 191:00 and 215:00 h:m after drug administration during Visit 3. |
Countries
Germany
Participant flow
Recruitment details
This was as an open-label, fixed-sequence trial with 2 treatments, administered to healthy male participants to compare itraconazole + BI 1015550 (T) with BI 1015550 alone (R). The BI 1015550 single doses of treatments R and T were separated by a wash-out period of at least 10 days.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensure that they (all participants) met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| BI 1015550 Alone (R) / Itraconazole + BI 1015550 (T) Participants were administered single dose of BI 1015550 6 milligram (mg) tablet orally with 240 milliLitre (mL) of water after an overnight fast of at least 10 hours on Day 1 of Visit 2. Again participants were administered itraconazole plus BI 1015550; participants received 12 days of itraconazole treatment (200 mg itraconazole solution given orally once daily with 240 mL of water after an overnight fast of at least 9 h) from Day -3 to Day 9 of Visit 3 combined with a single dose of 6 mg BI 1015550 on the fourth day (Day 1) of the itraconazole treatment (1 hour after the itraconazole administration). The BI 1015550 single doses of treatments R and T were separated by a wash-out period of at least 10 days. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | BI 1015550 Alone (R) / Itraconazole + BI 1015550 (T) |
|---|---|
| Age, Continuous | 42.3 Years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 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 | 16 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 5 / 16 | 5 / 16 | 9 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to 119 Hours
Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 to 119 hours (h) (AUC0-119). Standard error is actually geometric standard error. Geometric mean (gMean) is actually adjusted geometric mean. Pharmacokinetic samples were collected at 3:00 hours:minutes (h:m) prior to drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00 and 119:00 h:m after drug administration during Visit 2 and Visit 3. Additionally at 143:00, 167:00, 191:00 and 215:00 h:m after drug administration during Visit 3.
Time frame: Up to 215 hours (Please check measure description for detailed timeframe)
Population: Pharmacokinetic (PK) set (PKS):~The PKS included all subjects from the TS who provided at least 1 primary or secondary PK parameter that was not excluded. Thus, a subject was included in the PKS, even if he contributed only 1 PK parameter value for 1 period to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| itraconazole + BI 1015550 (T) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to 119 Hours | 2073.40 nanomole (nmol)*h/Litre (L) |
| BI 1015550 alone (R) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to 119 Hours | 933.44 nanomole (nmol)*h/Litre (L) |
Comparison: The analysis of variance (ANOVA) model included effects accounting for the following sources of variation: 'subject' and 'treatment'. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. No hypothesis was tested and no acceptance range was specified.90% CI: [203.47, 242.49]
Primary
Maximum Measured Concentration of the BI 1015550 in Plasma
Maximum measured concentration of the BI 1015550 in plasma (Cmax). Standard error is actually geometric standard error. Geometric mean is actually adjusted geometric mean. Pharmacokinetic samples were collected at 3:00 h:m prior to drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00 and 119:00 h:m after drug administration during Visit 2 and Visit 3. Additionally at 143:00, 167:00, 191:00 and 215:00 h:m after drug administration during Visit 3.
Time frame: Up to 215 hours (Please check measure description for detailed timeframe)
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| itraconazole + BI 1015550 (T) | Maximum Measured Concentration of the BI 1015550 in Plasma | 162.39 nmol/L |
| BI 1015550 alone (R) | Maximum Measured Concentration of the BI 1015550 in Plasma | 126.91 nmol/L |
Comparison: The analysis of variance (ANOVA) model included effects accounting for the following sources of variation: 'subject' and 'treatment'. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. No hypothesis was tested and no acceptance range was specified.90% CI: [117.65, 139.17]
Secondary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). Standard error is actually geometric standard error. Geometric mean is actually adjusted geometric mean. Pharmacokinetic samples were collected at 3:00 h:m prior to drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:00, 71:00, 95:00 and 119:00 h:m after drug administration during Visit 2 and Visit 3. Additionally at 143:00, 167:00, 191:00 and 215:00 h:m after drug administration during Visit 3.
Time frame: Up to 215 hours (Please check measure description for detailed timeframe)
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| itraconazole + BI 1015550 (T) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 2183.22 nmol*h/L |
| BI 1015550 alone (R) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 952.27 nmol*h/L |
Comparison: The analysis of variance (ANOVA) model included effects accounting for the following sources of variation: 'subject' and 'treatment'. The effect 'subject' was considered as random, whereas the effect 'treatment' was considered as fixed. No hypothesis was tested and no acceptance range was specified.90% CI: [207.82, 252.93]