Relative Bioavailability of BI 10773 and Glimepiride in Healthy Male Volunteers

Study Overview
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Brief Summary
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The objective was to investigate whether there was a drug-drug interaction between BI 10773 and glimepiride when co-administered. Therefore, the relative bioavailabilities of BI 10773 and glimepiride were determined when both drugs were given in combination compared to multiple oral doses of BI 10773 once daily alone and a single oral dose of glimepiride given alone.

Official Title
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Relative Bioavailability of Both BI 10773 and Glimepiride After Co-administration Compared to Multiple Oral Doses of BI 10773 (50 mg q.d.) Alone and a Single Dose of Glimepiride (1 mg) Alone in Healthy Male Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 10773
* Drug: Glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers 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 to 50 years (incl.) BMI (Body Mass Index) 18.5 to 29.9 kg/m2 (incl.) 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 of 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/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 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 30 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 Glucose-6-phosphate dehydrogenase deficiency

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence ABC<br>Treatment A: BI 10773 once daily from day 1 to 5 Treatment B: BI 10773 and glimepiride once on day 1 Treatment C: Glimepiride once on day 1 | Drug: BI 10773<br> <br> Drug: Glimepiride<br> <br> |
| Experimental: Sequence CAB<br>Treatment C: Glimepiride once on day 1 Treatment A: BI 10773 once daily from day 1 to 5 Treatment B: BI 10773 and glimepiride once on day 1 | Drug: BI 10773<br> <br> Drug: Glimepiride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773 |  | up to 5 days | 
| Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773 |  | up to 5 days | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) of glimepiride |  | up to 4 days | 
| Cmax (maximum measured concentration of the analyte in plasma) of glimepiride |  | up to 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) of glimepiride |  | up to 4 days | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) of glimepiride |  | up to 4 days | 
| λz (terminal rate constant in plasma) of glimepiride |  | up to 4 days | 
| t½ (terminal half-life of the analyte in plasma) of glimepiride |  | up to 4 days | 
| MRTpo (mean residence time of the analyte in the body after po administration) of glimepiride |  | up to 4 days | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) of glimepiride |  | up to 4 days | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of glimepiride |  | up to 4 days | 
| tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773 |  | up to 5 days | 
| Aet1-t2 (amount of analyte eliminated in urine over the time interval from t1 to t2) of glimepiride |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 | 
| fet1-t2 (fraction of analyte excreted unchanged in urine over the time interval from t1 to t2) of glimepiride |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 | 
| CLR (renal clearance of the analyte) of glimepiride |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 | 
| λz,ss (terminal rate constant of analyte in plasma at steady-state) of BI 10773 |  | up to 5 days | 
| t½,ss (terminal half-life of analyte in plasma at steady-state) of BI 10773 |  | up to 5 days | 
| MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) of BI 10773 |  | up to 5 days | 
| CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) of BI 10773 |  | up to 5 days | 
| Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) of BI 10773 |  | up to 5 days | 
| Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ) of BI 10773 |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5 | 
| fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ) of BI 10773 |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5 | 
| CLR,ss (renal clearance of the analyte at steady state) of BI 10773 |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5 | 
| UGE0-24 (Urinary glucose excretion of the analyte in urine over the time interval from time zero to 24 h) |  | 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on days 1 and 5 | 
| Number of patients with abnormal findings in physical examination |  | Baseline and within 3-14 days after last glimepiride administration | 
| Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate) |  | Baseline, day 1 and within 3-14 days after last glimepiride administration | 
| Number of patients with abnormal findings in 12-lead ECG (electrocardiogram) |  | Baseline, day 1 and within 3-14 days after last glimepiride administration | 
| Number of patients with abnormal findings in clinical laboratory tests |  | Baseline, day 1,4 and within 3-14 days after last glimepiride administration | 
| Number of patients with adverse events |  | Up to 34 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | Within 3-14 days after last glimepiride administration | 
| Number of patients with abnormal findings in glucose bedside tests |  | Pre-dose and 1, 2, 4, 7, 10, 14, 24 hours after glimepiride administration on day 1 |