Clinical trial NCT02256748: Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-06
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: AUC0-∞ of midazolam (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 13 days
measure: Cmax of midazolam (maximum concentration of midazolam in plasma)
timeFrame: up to 13 days
measure: AUC0-∞ of 1'-hydroxymidazolam (area under the concentration-time curve of 1'-hydroxymidazolam in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 13 days
measure: Cmax of 1'-hydroxymidazolam (maximum concentration of 1'-hydroxymidazolam in plasma)
timeFrame: up to 13 days
measure: AUC0-∞ ratio of 1'-hydroxymidazolam to midazolam
timeFrame: up to 13 days
Secondary outcomes:
measure: 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)
timeFrame: up to 13 days
measure: tmax (time from dosing to the maximum concentration of the analytes in plasma)
timeFrame: up to 13 days
measure: λz (terminal rate constant of the analytes in plasma)
timeFrame: up to 13 days
measure: t1/2 (terminal half-life of the analytes in plasma)
timeFrame: up to 13 days
measure: MRTpo (mean residence time of the analytes in the body after po administration)
timeFrame: up to 13 days
measure: CL/F (apparent clearance of the analytes in the plasma after extravascular administration)
timeFrame: up to 13 days
measure: Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose)
timeFrame: up to 13 days
measure: Pre-dose levels of BIRT 2584 XX and BI 610100
timeFrame: days 1, 3 and 12
measure: Number of subjects with abnormal findings in physical examination
timeFrame: up to 29 days
measure: Number of subjects with abnormal changes in laboratory parameters
timeFrame: up to 29 days
measure: Number of subjects with clinically significant changes in 12-lead ECG
timeFrame: up to 29 days
measure: Number of subjects with clinically significant changes in vital signs
timeFrame: up to 29 days
measure: Number of subjects with adverse events
timeFrame: up to 44 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: Day 29
Other outcomes:
Locations:
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