Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers
- Registration Number
- NCT02256748
- Lead Sponsor
- Boehringer Ingelheim
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BIRT 2584 XX + Midazolam BIRT 2584 XX BIRT 2584 XX: Multiple doses for 12 days (bid on days 1 and 2, qd from days 3 to 12) Midazolam: Administration on days -2, 1, 3, and 12 BIRT 2584 XX + Midazolam Midazolam BIRT 2584 XX: Multiple doses for 12 days (bid on days 1 and 2, qd from days 3 to 12) Midazolam: Administration on days -2, 1, 3, and 12
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 abnormal changes in laboratory parameters 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
Assessment of tolerability by investigator on a 4-point scale Day 29 Number of subjects with adverse events up to 44 days