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

Study Overview
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Brief Summary
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To assess the steady state pharmacokinetics of Desipramine with/without concomitant administration of Crobenetine.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Desipramine tablet
* Drug: Crobenetine infusion
* Drug: Placebo infusion


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. 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)

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
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Desipramine alone<br> | Drug: Desipramine tablet<br> <br> Drug: Placebo infusion<br> <br> |
| Experimental: Desipramine with Crobenetine<br> | Drug: Desipramine tablet<br> <br> Drug: Crobenetine infusion<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 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 |
| --- | --- | --- |
| 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 adverse events |  | 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 | 
| Number of subjects with clinically significant findings in 12-lead ECG |  | 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 |