Relative Bioavailability of BI 10773 and Glimepiride in Healthy Male Volunteers
- Registration Number
- NCT02172261
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 16
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sequence ABC BI 10773 1. Treatment A: BI 10773 once daily from day 1 to 5 2. Treatment B: BI 10773 and glimepiride once on day 1 3. Treatment C: Glimepiride once on day 1 Sequence ABC Glimepiride 1. Treatment A: BI 10773 once daily from day 1 to 5 2. Treatment B: BI 10773 and glimepiride once on day 1 3. Treatment C: Glimepiride once on day 1 Sequence CAB BI 10773 1. Treatment C: Glimepiride once on day 1 2. Treatment A: BI 10773 once daily from day 1 to 5 3. Treatment B: BI 10773 and glimepiride once on day 1 Sequence CAB Glimepiride 1. Treatment C: Glimepiride once on day 1 2. Treatment A: BI 10773 once daily from day 1 to 5 3. Treatment B: BI 10773 and glimepiride once on day 1
- Primary Outcome Measures
Name Time Method 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
Name Time Method λz (terminal rate constant in plasma) of glimepiride up to 4 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 tmax (time from dosing to the maximum concentration of the analyte 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 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 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