Metabolism and Pharmacokinetics of [14C]-BI 44370 BS Administered as an Oral Solution in Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to investigate the basic pharmacokinetics of BI 44370 BS, its metabolite CD 10419 BS, and 14C-radioactivity including mass balance, excretion pathways, and metabolism following a single oral administration of 200 mg [14C]BI 44370 BS to healthy male volunteers and to evaluate safety and tolerability following a single oral administration of 200 mg [14C]BI 44370 BS to healthy male volunteers

Official Title
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A Phase I Trial to Investigate the Metabolism and Pharmacokinetics of an Open Label Single Dose of 200 mg [14C]-BI 44370 BS Administered as an Oral Solution in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 44370 BS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males according to the following criteria based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG, clinical laboratory tests Age ≥18 and ≤65 years Body mass index (BMI) ≥18.0 and BMI ≤30.0 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation Exclusion Criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease 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 relevant allergy/hypersensitivity (including allergy to study drug or its excipients) Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration until after the last sample from Visit 2 is collected 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 during the stay in the trial centre Alcohol abuse (more than on average 2 units of alcoholic beverages per day or more than 14 units per week (1 unit equals 1 pint [285 mL] of beer or lager, 1 glass [125 mL] of wine, 25 mL shot of 40% spirit)) Drug abuse Blood donation (more than 100 mL within 60 days prior to study drug administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial until follow-up examination) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of study centre A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms) Veins unsuitable for blood sampling PR interval >220 ms or QRS interval >120 ms Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)), during work or during participation in a medical trial in the previous year Irregular defecation pattern (less than once per 2 days) Not willing to use adequate contraception (condoms use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device) during the whole study period from the time of the first intake of study drug until three months after the last intake

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 44370 BS<br>200 mg containing 2.43 megabecquerel (MBq) 14C-radioactivity | Drug: BI 44370 BS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual time course profiles of [14C]-radioactivity in whole blood, plasma, urine | in nmoleq/L | up to day 15 | 
| Individual time course profiles of [14C]-radioactivity in faeces | in nmoleq/kg | up to day 15 | 
| Individual time course profiles of BI 44370 BS (and its glucuronide CD 10419 BS) in plasma and urine |  | up to 15 days | 
| Rate and extent of excretion mass balance based on the total radioactivity in urine and faeces |  | up to 15 days | 
| Cblood cells/Cplasma ratio of [14C]-radioactivity |  | up to 12 hours after drug administration | 
| Cblood /Cplasma ratio of [14C]-radioactivity |  | up to 144 hours after drug administration | 
| Identification of major metabolites in plasma, urine, and faeces |  | up to day 15 | 
| Cmax (maximum concentration of the analyte(s) in plasma) |  | up to 144 hours after drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte(s) in plasma) |  | up to 144 hours after drug administration | 
| AUC0-tz (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 144 hours after drug administration | 
| AUC0-inf. (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to infinity) |  | up to 144 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | up to 144 hours after drug administration | 
| t1/2 (terminal half-life of the analyte(s) in plasma) |  | up to 144 hours after drug administration | 
| MRTpo (mean residence time of the analyte(s) in the body after oral administration) |  | up to 144 hours after drug administration | 
| CL/F (total clearance of the analyte in plasma after oral administration) |  | up to 144 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose) |  | up to 144 hours after drug administration | 
| Ae0-tz (amount of analyte that is eliminated in urine within the time interval zero to tz, additionally excretion within each sampling interval will be calculated) |  | up to 15 days | 
| fe0-tz (fraction of analyte excreted in urine within the time interval zero to tz in % of dose, additionally excretion within each sampling interval will be calculated) |  | up to 15 days | 
| Aefaeces,0-tz (amount of analyte excreted in faeces within the time interval zero to tz, additionally excretion within each sampling interval will be calculated) |  | up to 15 days | 
| fefaeces,0-tz (fraction of analyte excreted in faeces within the time interval zero to tz in % of dose, additionally excretion within each sampling interval will be calculated) |  | up to 15 days | 
| CLR,t1-t2 (renal clearance of analyte from the within the time interval t1 to t2) |  | up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinically relevant findings in vital signs |  | up to 23 days | 
| Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG) |  | up to 23 days | 
| Number of patients with clinically relevant laboratory findings |  | up to 23 days | 
| Number of patients with adverse events |  | up to up to 44 days | 
| Assessment of global tolerability on a 4-point scale |  | day 15 |