Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers

Study Overview
=================
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

Official Title
-----------------
A Study to Evaluate the Effect of Multiple Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BIRT 2584 XX
* Drug: Midazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIRT 2584 XX + Midazolam<br>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 | Drug: BIRT 2584 XX<br> <br> Drug: Midazolam<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Pulse rate, systolic, and diastolic blood pressure | up to 29 days | 
| Number of subjects with adverse events |  | up to 44 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | Day 29 |