Bioavailability of BI 1356 BS and Metformin After Co-administration Compared to the Bioavailability of BI 1356 BS Alone and Metformin Alone in Healthy Male Volunteers

Study Overview
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Brief Summary
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Investigate the bioavailability of BI 1356 BS and of metformin after concomitant multiple oral administration of 10 mg BI 1356 BS tablets and 3 x 850 mg metformin in comparison to BI 1356 BS and metformin given alone

Official Title
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Bioavailability of Both BI 1356 BS and Metformin After Co-administration Compared to the Bioavailability of Multiple Oral Doses of BI 1356 BS 10 mg Daily Alone and Metformin 850 mg Three Times a Day Alone in Healthy Male Volunteers (an Open-label, Randomized, Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Metformin
* Drug: BI 1356 BS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males according to the following criteria, based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests No finding deviating from normal and of clinical relevance No evidence of a clinically relevant concomitant disease Age ≥ 21 and Age ≤ 50 years BMI (Body Mass Index) ≥ 18.5 and ≤ 29.9 kg/m2 Ability to give signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and the local legislation Exclusion Criteria: 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 allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial by the investigator Intake of drugs with a long half-life (>24 hours) within one month or less than 10 half-lives of the respective drug prior to administration or during the conduct of this trial (review with clinical monitor if there is a question) Use of drugs which might reasonably influence the results of the trial (based on knowledge at the time of protocol preparation) within 10 days prior to administration or during the conduct of this trial Participation in another trial with an investigational drug within two months prior to administration or during the conduct of this trial Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) Inability to refrain from smoking during the conduct of this trial Alcohol abuse (more than 60 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the conduct of this trial) Excessive physical activities (within one week prior to administration or during the conduct of this trial) Any laboratory value outside the normal reference range that is of clinical relevance Inability to comply with the dietary regimen of the study center No adequate contraception (condom use plus another form of contraception e.g., spermicide, oral contraceptive taken by female partner, sterilization) during the whole study period from the time of the first intake of study drug until one month after the last intake of drug

Ages Eligible for Study
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Minimum Age: 21 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 |
| --- | --- |
| Active Comparator: Metformin<br> | Drug: Metformin<br> <br> |
| Experimental: BI 1356 BS and metformin<br>Daily administration of BI 1356 BS alone (day 1 to day 6) followed by the combined treatment of BI 1356 BS with metformin (day 7 to day 9) | Drug: Metformin<br> <br> Drug: BI 1356 BS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC) of the analytes in plasma at different time points |  | up to 240 hours after start of treatment | 
| Maximum concentration (Cmax) of the analytes in plasma at different time points |  | up to 240 hours after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from last dosing to maximum concentration of the analytes in plasma at steady state (tmax,ss) |  | up to 240 hours after start of treatment | 
| Minimum concentration of the analytes in plasma at steady state (Cmin,ss) over a uniform dosing interval τ |  | up to 240 hours after start of treatment | 
| Terminal rate constant of the analytes in plasma at steady state (λz,ss ) |  | up to 240 hours after start of treatment | 
| Terminal half-life of the analytes in plasma at steady state (t1/2,ss ) |  | up to 240 hours after start of treatment | 
| Mean residence time of the analytes in the body at steady state after oral administration (MRTpo,ss) |  | up to 240 hours after start of treatment | 
| Apparent clearance of the analytes in the plasma at steady state (CL/F,ss) following extravascular multiple dose administration |  | up to 240 hours after start of treatment | 
| Apparent volume of distribution during the terminal phase λz at steady state (Vz/F,ss) following extravascular administration |  | up to 240 hours after start of treatment | 
| Measurements of dipeptidylpeptidase 4 (DPP-IV) activity |  | up to 240 hours after start of treatment | 
| Number of patients with adverse events |  | up to 60 days | 
| Number of patients with clinically abnormal changes in laboratory values |  | Baseline, up to 14 days after last drug administration | 
| Number of patients with clinically relevant changes in vital signs |  | Baseline, up to 14 days after last drug administration | 
| feτ,ss (fraction of the dose excreted unchanged in urine at steady state) |  | 0-4 h, 4-8 h, 8-12 h and 12-24 hours after drug administration on days 3, 6, 9 | 
| CLR,ss (renal clearance of the analyte in plasma at steady state) |  | 0-4 h, 4-8 h, 8-12 h and 12-24 hours after drug administration on days 3, 6, 9 |