Safety, Tolerability and Pharmacokinetics of BI 44370 TA Oral Drinking Solution in Healthy Male Volunteers

Study Overview
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Brief Summary
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To evaluate the safety, tolerability and pharmacokinetics of single rising oral doses of BI 44370 TA in healthy male volunteers, to compare a drinking solution vs. a tablet formulation and to assess intra-individual pharmacokinetic (PK) variability by re-dosing two further doses.

Official Title
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Safety, Tolerability and Pharmacokinetics of BI 44370 TA Oral Drinking Solution in Healthy Male Volunteers (Dose Range: 5 - 800 mg). A Double-blind (Within Dose Groups), Randomised, Placebo-controlled Within Dose Groups, Single Rising Dose Study, Including Re-dosing at 100 mg and 500 mg (Solution) and at 200 mg (Four 50 mg Tablets)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 44370 TA solution
* Drug: BI 44370 TA tablet
* Drug: Placebo solution
* Drug: Placebo tablet


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 (BP, PR, RR and body temperature), 12-lead ECG, clinical laboratory tests Age ≥21 and Age ≤50 years Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 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 Blood Pressure (BP), Pulse Rate (PR), Respiratory rate (RR) , body temperature and Electrocardiogram(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 Surgery of the gastrointestinal tract (except appendectomy) 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 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 or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days 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 (more than 60 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of trial site A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms); A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Not willing to use adequate contraception (condom 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: 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 44370 TA solution<br> | Drug: BI 44370 TA solution<br> <br> |
| Experimental: BI 44370 TA tablet<br> | Drug: BI 44370 TA tablet<br> <br> |
| Placebo Comparator: Placebo solution<br> | Drug: Placebo solution<br> <br> |
| Placebo Comparator: Placebo tablet<br> | Drug: Placebo tablet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | up to 10 days after last drug administration | 
| Number of patients with clinically significant findings in vital signs |  | up to 10 days after last drug administration | 
| Number of patients with clinically significant findings in laboratory tests |  | up to 10 days after last drug administration | 
| Number of patients with clinically significant findings in ECG |  | up to 10 days after last drug administration | 
| Assessment of tolerability by investigator on a 4-point scale |  | up to 10 days after last drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 72 hours after drug administration | 
| tmax (time from dosing to maximum measured concentration) |  | up to 72 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 72 hours after drug administration | 
| %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | up to 72 hours after drug administration | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 72 hours after drug administration | 
| AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2) |  | up to 72 hours after drug administration | 
| tz (time of last measurable concentration of the analyte in plasma) |  | up to 72 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 72 hours after drug administration | 
| MRTp.o. (mean residence time of the analyte in the body after oral administration) |  | up to 72 hours after drug administration | 
| CL/F (total/apparent clearance of the analyte in plasma after extravascular administration) |  | up to 72 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase tz following an extravascular dose) |  | up to 72 hours after drug administration | 
| λz (the terminal rate constant) |  | up to 72 hours after drug administration | 
| Aet1/t2 (total quantity of analyte excreted in the urine in the time interval from t1 to t2) |  | up to 24 hours after drug administration | 
| fet1/t2 (the fractional excretion of the analyte in the time interval from t1 to t2) |  | up to 24 hours after drug administration | 
| CLR,t1/t2 (the renal clearance of the analyte in the time interval from t1 to t2) |  | up to 24 hours after drug administration |