Clinical trial NCT02172248: Relative Bioavailability BI 10773 and Metformin in Healthy Male Volunteers
Official title: Relative Bioavailability of Both BI 10773 and Metformin After Coadministration Compared to Multiple Oral Doses of BI 10773 (50 mg q.d.) Alone and Metformin (1000 mg b.i.d.) Alone to 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: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective was to investigate a possible drug-drug interaction between BI 10773 and metformin when co-administered as multiple oral doses. Therefore, the relative bioavailabilities of BI 10773 and metformin were determined when both drugs were given in combination compared with BI 10773 or metformin 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 (Blood Pressure), PR (Pulse Rate)), 12-lead ECG (Electrocardiogram), 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, 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
* 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

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)
timeFrame: up to 7 days
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: up to 7 days
Secondary outcomes:
measure: C24,N (concentration of analyte in plasma at 24 hours post-drug administration after administration of the Nth dose) of BI 10773
timeFrame: up to 7 days
measure: C12,N (concentration of analyte in plasma at 12 hours post-drug administration after administration of the Nth dose) of metformin
timeFrame: up to 7 days
measure: λz,ss (terminal half-life of the analyte in plasma)
timeFrame: up to 7 days
measure: t½,ss (terminal half-life of the analyte in plasma at steady state)
timeFrame: up to 7 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)
timeFrame: up to 7 days
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)
timeFrame: up to 7 days
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
timeFrame: up to 7 days
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration)
timeFrame: up to 7 days
measure: Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: CLR,ss (renal clearance of the analyte at steady state) of BI 10773 and metformin
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: Urinary glucose excretion (UGE)
timeFrame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing
measure: Number of patients with abnormal findings in physical examination
timeFrame: Baseline and within 3-14 days after last study drug 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 study drug administration
measure: Number of patients with abnormal findings in 12-lead ECG (electrocardiogram)
timeFrame: Baseline and within 3-14 days after last study drug administration
measure: Number of patients with abnormal changes in clinical laboratory tests
timeFrame: Baseline, day 1, 4, 5 and within 3-14 days after last study drug administration
measure: Number of patients with adverse events
timeFrame: up to 40 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: Within 3-14 days after last study drug administration
Other outcomes:
Locations:
Study officials:
References: