Relative Bioavailability of BI 10773 Administered Twice Daily Compared BI 10773 Given Once Daily After Multiple Oral Doses in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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To investigate the influence of different dosage regimen (5 mg twice daily versus 10 mg once daily) on the steady state pharmacokinetics and pharmacodynamics of BI 10773 administered orally

Official Title
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Relative Bioavailability of 5 mg BI 10773 Administered Twice Daily Compared to 10 mg BI 10773 Given Once Daily After Multiple Oral Doses in Healthy Male and Female Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Empagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests Age = 18 and Age = 50 years BMI = 18.5 and = 29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with 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 Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 6. 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 within one month or less than 10 half-lives of the respective drug prior to first study drug administration except if a relevant interaction can be ruled out 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 (average consumption of more than 20 g/day in females and 30 g/day in males) Drug abuse Blood donation (more than 100 mL within four weeks prior to the start of study) 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 TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) For female subjects: Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 1 month after study completion No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD A record of all subjects screened, in- or excluded, will be maintained. (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide) Lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Empagliflozin<br>5 mg bid | Drug: Empagliflozin<br>* 5 days of treatment with 5 mg BI 10773 bid until steady state<br>|
| Experimental: Treatment B: Empagliflozin<br>10 mg qd | Drug: Empagliflozin<br>* 5 days of treatment with 10 mg BI 10773 qd until steady state<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the concentration-time curve of the analyte in plasma) - AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) for 10 mg BI 10773 QD. |  | up to 168 hours | 
| AUC (area under the concentration-time curve of the analyte in plasma) - AUC0-24,ss (area under the concentration-time curves of the analyte in plasma at steady-state over two dosing intervals) for 5 mg BI 10773 BID after the morning dose on Day 5. |  | up to 168 hours | 
| AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773. |  | up to 168 hours | 
| Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773. |  | up to 168 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C12,N (concentration of analyte in plasma at 12 hours post-drug administration after administration of the Nth dose for the BID regimen) of BI 10773. |  | up to 168 hours | 
| C24,N (concentration of analyte in plasma at 24 hours post-drug administration after administration of the Nth dose for the QD regimen) of BI 10773. |  | up to 168 hours | 
| Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773 |  | up to 168 hours | 
| Cavg (average concentration of the analyte in plasma at steady state) of BI 10773 |  | up to 168 hours | 
| ¿z,ss (terminal half-life of the analyte in plasma at steady state) of BI 10773 |  | up to 168 hours | 
| t½,ss (terminal half-life of the analyte in plasma at steady state) of BI 10773 |  | up to 168 hours | 
| tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval t) of BI 10773. |  | up to 168 hours | 
| MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) of BI 10773. |  | up to 168 hours | 
| CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) of BI 10773. |  | up to 168 hours | 
| Vz/F,ss (apparent volume of distribution during the terminal phase tau z at steady state following extravascular administration) of BI 10773. |  | up to 168 hours | 
| PTF (percentage peak-trough fluctuation) |  | up to 168 hours |