Pharmacokinetics of Oral Desipramine With and Without Concomitant Administration of Crobenetine Infusion in Healthy Male Subjects

Pharmacokinetics of 50 mg Desipramine Daily, Given Orally Over 7 Days 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 Randomized, Placebo Controlled, Single Blind (for Crobenetine), Two-way Cross Over Trial in Healthy Male Subjects

To assess the steady state pharmacokinetics of Desipramine with/without concomitant administration of Crobenetine.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Desipramine tablet; Drug: Placebo infusion; Drug: Crobenetine infusion

• Study Type: Interventional
• Enrollment (Actual): 24
• 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.

In accordance with Good Clinical Practice and local legislation all volunteers will have given their written informed consent prior to admission to the study.

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
• Use of any drugs which 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
• Cytochrome P450 2D6 poor metaboliser (to be determined by phenotyping or genotyping)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Desipramine alone	Drug: Desipramine tablet; Drug: Placebo infusion
Experimental: Desipramine with Crobenetine	Drug: Desipramine tablet; Drug: Crobenetine infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration time curve for desipramine at steady state (AUC,ss)	up to 168 hours after start of drug administration
Maximum plasma concentration of desipramine at steady state (Cmax,ss)	up to 168 hours after start of drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events		up to 8 days after last drug administration
Number of subjects with clinically significant findings in laboratory tests		up to 8 days after last drug administration
Number of subjects with clinically significant findings in vital signs	blood pressure, pulse rate	up to 8 days after last drug administration
Individual time courses of plasma concentrations		up to 168 hours after start of drug administration
Area under the concentration time curve from zero time to time of last quantifiable drug concentration (AUC0-tz)		up to 168 hours after start of drug administration
Area under the concentration time curve from zero time extrapolated to infinity(AUC0-infinity)		up to 168 hours after start of drug administration
Time to reach maximum concentration of desipramine at steady state (tmax,ss)		up to 168 hours after start of drug administration
Apparent terminal rate constant (λz)		up to 168 hours after start of drug administration
Apparent terminal half-live in plasma (t1/2)		up to 168 hours after start of drug administration
Mean residence time (MRT)		up to 168 hours after start of drug administration
Total clearance (CL)		up to 168 hours after start of drug administration
Apparent volume of distribution (V)		up to 168 hours after start of drug administration
Observed concentration of crobenetine (C,h)		1 and 6 hours after start of infusion
Number of subjects with clinically significant findings in 12-lead ECG		up to 8 days after last 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 23, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Estimate): October 24, 2014
• Last Update Submitted That Met QC Criteria: October 23, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Desipramine
• Other Study ID Numbers: 599.11