Healthy
Conditions
Brief summary
In order to assess the potential impact of steady state BI 425809 on CYP3A clinically, the effect of BI 425809 on the midazolam pharmacokinetics will be evaluated. Midazolam is a recommended substrate of CYP3A4.
Interventions
DRUGmidazolam
midazolam
DRUGiclepertin (BI 425809)
BI 425809
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SEQUENTIAL
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, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 55 years (inclusive) * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
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 millimetre of mercury (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 Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Plasma concentrations of midazolam were measured within 1 hour (h) before and at 30 minutes (min), 1h, 1h 30 min, 2h, 3h, 4h, 6h, 8h, 10h, and 12h after administration of midazolam alone or in combination with iclepertin (BI 425809). | Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. |
| Maximum Measured Concentration of Midazolam in Plasma (Cmax) | Plasma concentrations of midazolam were measured within 1 hour (h) before and at 30 minutes (min), 1h, 1h 30 min, 2h, 3h, 4h, 6h, 8h, 10h, and 12h after administration of midazolam alone or in combination with iclepertin (BI 425809). | Maximum measured concentration of midazolam in plasma (Cmax) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Plasma concentrations of midazolam were measured within 1 hour (h) before and at 30 minutes (min), 1h, 1h 30 min, 2h, 3h, 4h, 6h, 8h, 10h, and 12h after administration of midazolam alone or in combination with iclepertin (BI 425809). | Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented. |
Countries
Germany
Participant flow
Recruitment details
This Phase I drug-drug interaction trial was performed as a non-randomised, open-label, two-period, crossover, one-sequence trial in order to investigate the effect of the offender drug iclepertin on the victim drug midazolam, based on an intra-subject comparison in healthy male subjects.
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 | 38.6 Years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 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 | 15 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 | 0 / 12 |
| other Total, other adverse events | 0 / 15 | 5 / 14 | 1 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 12 |
Outcome results
None listed