Metabolism and Pharmacokinetics of [14C]-DK-AH 269 CL in 12 Healthy Male Volunteers

Study Overview
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Brief Summary
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To investigate absorption, metabolism and excretion of [14C]-DK-AH 269 CL after oral and intravenous administration in healthy volunteers To assess the safety and tolerability of DK-AH 269 CL after oral and intravenous administration to healthy volunteers

Official Title
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Metabolism and Pharmacokinetics of [14C]-DK-AH 269 CL After Administration of Single Doses of 5 mg [14C]-DK-AH 269 CL Intravenously and 10 mg [14C]-DK-AH 269 CL as Oral Solution in a Parallel-group Design in 12 Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: [14C]-DK-AH 269 CL, solution for infusion
* Drug: [14C]-DK-AH 269 CL, drinking solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50 to 65 years of age Body Mass Index (BMI) of 19.9 to 29.9 kg/m2 Resting heart rate (HR) (after 5 min. in the supine position) of more than 55 bpm All volunteers will have given their written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation. Exclusion Criteria: Any finding at the medical examination (including BP, HR and ECG) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, hematological/oncological, immunological or hormonal disorders Diseases of the central nervous system 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 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 two weeks prior to administration or during the trial Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation (≥ 100 mL within 2 months prior to administration or during the trial) Excessive physical activities (within the last week before the study) Any laboratory value outside the reference range and of clinical relevance Inability to comply with dietary regimen of study centre Not necessarily clinically relevant abnormalities, but specific exclusion criteria for the drugs under study or for the study: Subjects at increased risk for development of cardiac arrhythmia (e.g. family history of long QT syndrome or sudden cardiac death) ECG: PR interval > 210 ms HR at rest ≤ 55 beats per minute (bpm) Relevant ophthalmological disease

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: [14C]-DK-AH 269 CL intravenous<br> | Drug: [14C]-DK-AH 269 CL, solution for infusion<br> <br> |
| Experimental: [14C]-DK-AH 269 CL oral<br> | Drug: [14C]-DK-AH 269 CL, drinking solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration of the analytes in plasma (Cmax) |  | Up to 96 hours after start of treatment | 
| Area under the concentration-time curve of the analytes in plasma (AUC) |  | Up to 96 hours after start of treatment | 
| Time from dosing to the maximum concentration of the analytes in plasma (tmax) |  | Up to 96 hours after start of treatment | 
| Terminal rate constant of the analytes in plasma (λz) |  | Up to 96 hours after start of treatment | 
| Terminal half-life of the analytes in plasma (t1/2) |  | Up to 96 hours after start of treatment | 
| Mean residence time of the analytes in the body after intravenous administration (MRT) |  | Up to 96 hours after start of treatment | 
| Mean residence time of the analytes in the body after oral administration (MRTpo) |  | Up to 96 hours after start of treatment | 
| Apparent clearance of the analytes in plasma following extravascular administration (CL/F) |  | Up to 96 hours after start of treatment | 
| Total clearance of the analytes in plasma following intravascular administration (CL) |  | Up to 96 hours after start of treatment | 
| Apparent volume of distribution of the analytes during the terminal phase λz following extravascular administration (Vz/F) |  | Up to 96 hours after start of treatment | 
| Volume of distribution at steady state (Vss) |  | Up to 96 hours after start of treatment | 
| Fraction of analytes eliminated in urine from 0 to the time of the last quantifiable data point (fe0-tz) |  | Up to 120 hours after start of treatment | 
| Fraction of analytes eliminated in faeces from 0 to the time of the last quantifiable data point (fefaeces,0-tz) |  | Up to 120 hours after start of treatment | 
| Renal clearance of the analytes from 0 to the time of the last quantifiable data point (CLR,0-tz) |  | Up to 120 hours after start of treatment | 
| Fraction of dose absorbed, based on radioactivity data (Fa) |  | Up to 96 hours after start of treatment | 
| Absolute bioavailability of the analytes after oral administration (F) |  | Up to 96 hours after start of treatment | 
| Ratio of CBlood cells/Cplasma [14C]-radioactivity |  | Up to 96 hours after start of treatment | 
| Number of patients with clinically significant findings in vital signs | blood pressure, heart rate | up to 12 days after last drug administration | 
| Number of patients with clinically significant findings in 12-lead ECG |  | up to 12 days after last drug administration | 
| Number of patients with clinically significant findings in 2-lead ECG (telemetry) |  | up to 90 minutes after start of treatment | 
| Clinically significant changes from baseline in physical examination |  | Pre-dose, and 12 days after last drug administration | 
| Occurrence of visual phenomena | questionnaire | up to 120 hours after start of treatment | 
| Number of patients with clinically significant findings in clinical laboratory tests |  | up to 12 days after last drug administration |