Bioavailability and Pharmacokinetics of BI 10773 Tablet in Healthy Male Volunteers

Study Overview
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Brief Summary
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Trial to assess the effect of food on the pharmacokinetics and the extent of absorption of a single dose BI 10773 tablet in healthy subjects

Official Title
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The Effect of Food on the Bioavailability and Pharmacokinetics of BI 10773 Tablet, Administered as a Single Dose of 50 mg With and Without Food to Healthy Male Volunteers in an Open-label, Randomised Intraindividual Crossover Comparison Design

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 10773


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, HR), 12-lead ECG, clinical laboratory tests Age ≥ 18 and Age ≤ 55 years BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation Exclusion Criteria: Any finding in the medical examination (including BP (blood pressure), PR (pulse rate) and ECG (electrocardiogram)) 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 or 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 the 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 de pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome) Elevated urinary glucose levels at screening (> 15 mg/dl; > 0.83 mmol/L)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 10773 tablet administered with food<br>50 mg BI 10773 after a standardised high fat breakfast | Drug: BI 10773<br> <br> |
| Active Comparator: BI 10773 tablet administered to fasted subjects<br>50 mg BI 10773 p.o. after an overnight fast of at least 10 hours | Drug: BI 10773<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| t1/2 (terminal half-life of the analyte in plasma) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours after last dose | 
| %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| 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) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| λz (terminal rate constant in plasma) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| MRTpo (mean residence time of the analyte in the body after p.o. administration) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose | 
| Glucose excretion in urine |  | pre-dose and 0-4, 4-8, 8-12, 12-24 hours post-dose | 
| Creatinine excretion in urine |  | pre-dose and 0-4, 4-8, 8-12, 12-24 hours post-dose | 
| Abnormal findings in physical examination |  | Baseline and within 14 days after last trial procedure | 
| Changes from baseline in vital signs (blood pressure, pulse rate) |  | Baseline and within 14 days after last trial procedure | 
| Changes from baseline in 12-lead ECG (electrocardiogram) |  | Baseline and within 14 days after last trial procedure | 
| Changes from baseline in routine laboratory tests |  | Baseline and within 14 days after last trial procedure | 
| Incidence of adverse events |  | Up to 15 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | Within 14 days after last trial procedure |