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

Study Overview
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Brief Summary
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To assess the pharmacokinetics of midazolam with/without concomitant administration of crobenetine

Official Title
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Pharmacokinetics of 7.5 mg Midazolam, Given Orally With and Without Concomitant Administration of 175 mg Crobenetine, Given as a 6 Hrs i.v. Infusion (One Hour Loading Dose Directly Followed by a Five Hours Maintenance Dose). A Randomised, Single Blind, Two-way Crossover Trial in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Midazolam, tablet
* Drug: Crobenetine, i.v. infusion
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam and crobenetine<br> | Drug: Midazolam, tablet<br> <br> Drug: Crobenetine, i.v. infusion<br> <br> |
| Placebo Comparator: Midazolam and placebo<br> | Drug: Midazolam, tablet<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Maximum observed concentration of midazolam in plasma (Cmax) |  | up to 24 hours after start of drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Individual time courses of plasma concentrations |  | up to 24 hours after start of drug administration | 
| Terminal rate constant in plasma (λz) |  | up to 24 hours after start of 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 | 
| Volume of distribution (V) |  | up to 24 hours after start of drug administration | 
| Changes from baseline in physical examination |  | pre-dose and day 8 after drug administration | 
| Number of patients with clinically relevant findings in vital signs | blood pressure, pulse rate | up to day 8 after drug administration | 
| Number of patients with clinically relevant findings in 12-lead ECG |  | up to day 8 after drug administration | 
| 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 | 
| Global assessment of tolerability by the investigator on a 4-point rating scale |  | up to 192 hours after start of drug administration |