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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Midazolam, tablet; Drug: Crobenetine, i.v. infusion

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam and crobenetine	Drug: Midazolam, tablet; Drug: Crobenetine, i.v. infusion
Placebo Comparator: Midazolam and placebo	Drug: Placebo; Drug: Midazolam, tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): April 1, 2002

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimate): October 21, 2014

Study Record Updates

• Last Update Posted (Estimate): October 21, 2014
• Last Update Submitted That Met QC Criteria: October 20, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 599.12