Healthy
Conditions
Brief summary
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.
Interventions
DRUGBI 10773
DRUGGlimepiride
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax (maximum measured concentration of the analyte in plasma) of glimepiride | up to 4 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 |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Outcome results
None listed