Clinical trial NCT02172261: Relative Bioavailability of BI 10773 and Glimepiride in Healthy Male Volunteers
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: up to 5 days
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) of BI 10773
timeFrame: up to 5 days
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) of glimepiride
timeFrame: up to 4 days
measure: Cmax (maximum measured concentration of the analyte in plasma) of glimepiride
timeFrame: up to 4 days
Secondary outcomes:
measure: 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
timeFrame: up to 4 days
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma) of glimepiride
timeFrame: up to 4 days
measure: λz (terminal rate constant in plasma) of glimepiride
timeFrame: up to 4 days
measure: t½ (terminal half-life of the analyte in plasma) of glimepiride
timeFrame: up to 4 days
measure: MRTpo (mean residence time of the analyte in the body after po administration) of glimepiride
timeFrame: up to 4 days
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration) of glimepiride
timeFrame: up to 4 days
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of glimepiride
timeFrame: up to 4 days
measure: 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
timeFrame: up to 5 days
measure: Aet1-t2 (amount of analyte eliminated in urine over the time interval from t1 to t2) of glimepiride
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1
measure: fet1-t2 (fraction of analyte excreted unchanged in urine over the time interval from t1 to t2) of glimepiride
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1
measure: CLR (renal clearance of the analyte) of glimepiride
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1
measure: λz,ss (terminal rate constant of analyte in plasma at steady-state) of BI 10773
timeFrame: up to 5 days
measure: t½,ss (terminal half-life of analyte in plasma at steady-state) of BI 10773
timeFrame: up to 5 days
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) of BI 10773
timeFrame: up to 5 days
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) of BI 10773
timeFrame: up to 5 days
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) of BI 10773
timeFrame: up to 5 days
measure: Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ) of BI 10773
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5
measure: fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ) of BI 10773
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5
measure: CLR,ss (renal clearance of the analyte at steady state) of BI 10773
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on day 1 and 5
measure: UGE0-24 (Urinary glucose excretion of the analyte in urine over the time interval from time zero to 24 h)
timeFrame: 1 hour pre-dose and 0-2, 2-4, 4-8, 8-12, 12-24 after administration on days 1 and 5
measure: Number of patients with abnormal findings in physical examination
timeFrame: Baseline and within 3-14 days after last glimepiride administration
measure: Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate)
timeFrame: Baseline, day 1 and within 3-14 days after last glimepiride administration
measure: Number of patients with abnormal findings in 12-lead ECG (electrocardiogram)
timeFrame: Baseline, day 1 and within 3-14 days after last glimepiride administration
measure: Number of patients with abnormal findings in clinical laboratory tests
timeFrame: Baseline, day 1,4 and within 3-14 days after last glimepiride administration
measure: Number of patients with adverse events
timeFrame: Up to 34 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: Within 3-14 days after last glimepiride administration
measure: Number of patients with abnormal findings in glucose bedside tests
timeFrame: Pre-dose and 1, 2, 4, 7, 10, 14, 24 hours after glimepiride administration on day 1
Other outcomes:
Locations:
Study officials:
References: