Clinical trial NCT02269202: Pharmacokinetics of Midazolam, With and Without Concomitant Administration of Crobenetine in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-21
Enrollment: 20
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: To assess the pharmacokinetics of midazolam with/without concomitant administration of crobenetine


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-time curve of midazolam from zero time extrapolated to infinity (AUC0-infinity)
timeFrame: up to 24 hours after start of drug administration
measure: Maximum observed concentration of midazolam in plasma (Cmax)
timeFrame: up to 24 hours after start of drug administration
Secondary outcomes:
measure: Area under the concentration-time curve (AUC)
timeFrame: up to 24 hours after start of drug administration
measure: Time to maximum observed concentration (tmax)
timeFrame: up to 24 hours after start of drug administration
measure: Individual time courses of plasma concentrations
timeFrame: up to 24 hours after start of drug administration
measure: Terminal rate constant in plasma (λz)
timeFrame: up to 24 hours after start of drug administration
measure: Terminal half-life in plasma (t1/2)
timeFrame: up to 24 hours after start of drug administration
measure: Mean residence time in the body (MRT)
timeFrame: up to 24 hours after start of drug administration
measure: Apparent clearance in plasma (CL/F)
timeFrame: up to 24 hours after start of drug administration
measure: Volume of distribution (V)
timeFrame: up to 24 hours after start of drug administration
measure: Changes from baseline in physical examination
timeFrame: pre-dose and day 8 after drug administration
measure: Number of patients with clinically relevant findings in vital signs
timeFrame: up to day 8 after drug administration
measure: Number of patients with clinically relevant findings in 12-lead ECG
timeFrame: up to day 8 after drug administration
measure: Number of patients with clinically relevant findings in laboratory tests
timeFrame: up to day 8 after drug administration
measure: Number of patients with adverse events
timeFrame: up to day 8 after drug administration
measure: Global assessment of tolerability by the investigator on a 4-point rating scale
timeFrame: up to 192 hours after start of drug administration
Other outcomes:
Locations:
Study officials:
References: