Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the effect on the exposure of BI 1815368 in plasma when given as oral single dose together with multiple oral doses of itraconazole (Test, T) as compared to when given alone as oral single dose (Reference, R).
Interventions
DRUGBI 1815368
BI 1815368
DRUGItraconazole
Itraconazole
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants cross over from test treatment (T) to reference treatment (R) (two periods, fixed sequence).
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, as based on a complete medical history including a physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, and clinical laboratory tests * Age of 18 to 55 years (inclusive) * Body mass index (BMI) of 18.5 to 29.9 kilograms per square meter (kg/m\^2) (inclusive) * Signed and dated written informed consent in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Exclusion criteria
* Any finding in the medical examination (including blood pressure, pulse rate or electrocardiogram) deviating from normal and assessed as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimeter 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 * Relevant chronic or acute infections Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1815368 Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours prior to and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, and 71 hours for both periods, and additionally at 95, 119 and 143 hours for Period 2 after BI 1815368 administration. | Area under the concentration-time curve of BI 1815368 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. Geometric least squares mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance model (ANOVA) on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included 'subjects' as a random effect and treatment as a fixed effect. These quantities were then back transformed to the original scale to provide the point estimate and 90% confidence intervals (CIs) for each endpoint. |
| Maximum Measured Concentration of BI 1815368 in Plasma (Cmax) | Within 3 hours prior to and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, and 71 hours for both periods, and additionally at 95, 119 and 143 hours for Period 2 after BI 1815368 administration. | Maximum measured concentration (Cmax) of BI 1815368 in plasma is reported. Geometric least squares mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance model (ANOVA) on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included 'subjects' as a random effect and treatment as a fixed effect. These quantities were then back transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1815368 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours prior to and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, and 71 hours for both periods, and additionally at 95, 119 and 143 hours for Period 2 after BI 1815368 administration. | Area under the concentration-time curve of BI 1815368 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. Geometric least squares mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance model (ANOVA) on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included 'subjects' as a random effect and treatment as a fixed effect. These quantities were then back transformed to the original scale to provide the point estimate and 90% CIs for each endpoint. |
Countries
Germany
Participant flow
Recruitment details
This study was an open-label, single-center, two-period, fixed-sequence trial in healthy male subjects. Each subject participated in two treatment periods (Days -3 to 4 in Period 1 and Days -3 to 7 in Period 2) and received the Reference treatment (R) in Period 1 and the Test treatment (T) in Period 2.
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.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39.6 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 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 |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 4 / 14 | 2 / 14 | 4 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 13 |
Outcome results
None listed