Pharmacokinetics of Midazolam, With and Without Concomitant Administration of Crobenetine in Healthy Male Subjects

Recruitment & Eligibility

Inclusion Criteria

All participants in the study should be healthy males, range from 21 to 50 years of age and their bodymass index (BMI) be within 18.5 to 29.9 kg/m2

Exclusion Criteria

Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
History of relevant orthostatic hypotension, fainting spells or blackouts
Chronic or relevant acute infections
History of allergy/hypersensitivity (including drug allergy), which is deemed relevant to the trial as judged by the investigator
Intake of drugs with a long half-life (> 24 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study (except substitution therapy regarding thyroid gland)
Use of any drugs that might influence the results of the trial (within one week prior to administration or during the trial)
Participation in another trial with an investigational drug (within two months prior to administration or during the trial)
Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
Inability to refrain from smoking on trial days
Alcohol abuse (> 60 g/day)
Drug abuse
Blood donation (≥ 100 mL, within four weeks prior to administration or during the trial)
Excessive physical activities (within the last week before the study)
Any laboratory value outside the reference range of clinical relevance

Study & Design

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Maximum observed concentration of midazolam in plasma (Cmax)	up to 24 hours after start of drug administration
Area under the concentration-time curve of midazolam from zero time extrapolated to infinity (AUC0-infinity)	up to 24 hours after start of drug administration

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve (AUC)	up to 24 hours after start of drug administration
Time to maximum observed concentration (tmax)	up to 24 hours after start of drug administration
Volume of distribution (V)	up to 24 hours after start of drug administration
Number of patients with clinically relevant findings in 12-lead ECG	up to day 8 after drug administration
Global assessment of tolerability by the investigator on a 4-point rating scale	up to 192 hours after start of drug administration
Terminal rate constant in plasma (λz)	up to 24 hours after start of drug administration
Individual time courses of plasma concentrations	up to 24 hours after start of drug administration
Changes from baseline in physical examination	pre-dose and day 8 after drug administration
Terminal half-life in plasma (t1/2)	up to 24 hours after start of drug administration
Mean residence time in the body (MRT)	up to 24 hours after start of drug administration
Apparent clearance in plasma (CL/F)	up to 24 hours after start of drug administration
Number of patients with clinically relevant findings in vital signs	up to day 8 after drug administration	blood pressure, pulse rate
Number of patients with clinically relevant findings in laboratory tests	up to day 8 after drug administration
Number of patients with adverse events	up to day 8 after drug administration

Recruitment & Eligibility