Healthy
Conditions
Brief summary
The objective of the study was to investigate the effect of BIRT 2584 XX and its metabolite BI 610100 when BIRT 2584 XX is administered as a tablet to near steady state in estimated high therapeutic dose on the pharmacokinetics (PK) of midazolam, a probe substrate for CYP3A4. The PK of midazolam was measured before dosing of BIRT 2584 XX, after a single dose of BIRT 2584 XX and after repeated doses of BIRT 2584 XX for 3 and 12 days
Interventions
DRUGBIRT 2584 XX
DRUGMidazolam
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 as determined by results of the screening * Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation * Age ≥ 18 and ≤ 55 years * BMI ≥ 18.5 and ≤ 29.9 kg/m2
Exclusion criteria
* Any finding during the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, oncological, or hormonal disorders * Surgery of gastrointestinal tract (except appendectomy) * Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders * Relevant history of orthostatic hypotension, fainting spells, or blackouts * Chronic or relevant acute infections * History of allergy/hypersensitivity (including drug allergy) considered relevant to the trial as judged by the investigator * Intake of drugs with a long half-life (greater than 24 hours) (less than 1 month prior to administration or during the trial) * Use of any drugs, which might influence the results of the trial (less than 10 days prior to study drug administration or expected during the trial) * Participation in another trial with an investigational drug (less than 2 months prior to administration or expected during trial) * Smoker (more than 10 cigarettes/day or more than 3 cigars/day or more than 3 pipes/day) * Alcohol abuse (more than 60 g of ethanol per day) * Drug abuse * Blood donation or loss greater than 400 mL (less than 1 month prior to administration or expected during the trial) * Clinically relevant laboratory abnormalities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC0-∞ of midazolam (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity) | up to 13 days |
| Cmax of midazolam (maximum concentration of midazolam in plasma) | up to 13 days |
| AUC0-∞ of 1'-hydroxymidazolam (area under the concentration-time curve of 1'-hydroxymidazolam in plasma over the time interval from 0 extrapolated to infinity) | up to 13 days |
| Cmax of 1'-hydroxymidazolam (maximum concentration of 1'-hydroxymidazolam in plasma) | up to 13 days |
| AUC0-∞ ratio of 1'-hydroxymidazolam to midazolam | up to 13 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRTpo (mean residence time of the analytes in the body after po administration) | up to 13 days | — |
| CL/F (apparent clearance of the analytes in the plasma after extravascular administration) | up to 13 days | — |
| Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose) | up to 13 days | — |
| Pre-dose levels of BIRT 2584 XX and BI 610100 | days 1, 3 and 12 | — |
| Number of subjects with abnormal findings in physical examination | up to 29 days | — |
| Number of subjects with clinically significant changes in 12-lead ECG | up to 29 days | — |
| Number of subjects with clinically significant changes in vital signs | up to 29 days | Pulse rate, systolic, and diastolic blood pressure |
| Number of subjects with adverse events | up to 44 days | — |
| Assessment of tolerability by investigator on a 4-point scale | Day 29 | — |
| Number of subjects with abnormal changes in laboratory parameters | up to 29 days | — |
| AUC0-tz (area under the concentration-time curve of the analytes in plasma over the time interval from 0 to the time of the last quantifiable data point) | up to 13 days | — |
| tmax (time from dosing to the maximum concentration of the analytes in plasma) | up to 13 days | — |
| λz (terminal rate constant of the analytes in plasma) | up to 13 days | — |
| t1/2 (terminal half-life of the analytes in plasma) | up to 13 days | — |
Outcome results
None listed