Healthy
Conditions
Brief summary
Study to demonstrate bioequivalence of a 2.5 mg linagliptin/1000 mg metformin fixed-dose combination (FDC) tablet compared with single tablets of linagliptin 2.5 mg and metformin 1000 mg administered together.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy men and women according to the following criteria: based upon a complete medical history, including physical examination, vital signs (Blood pressure (BP), Pulse Rate (PR)), 12-lead ECG, clinical laboratory tests 2. Age 18 to 55 years (inclusive) 3. Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) 4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Surgery of the gastrointestinal tract (except appendectomy) 5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 6. History of relevant orthostatic hypotension, fainting spells or blackouts 7. Chronic or relevant acute infections 8. History of relevant allergy or hypersensitivity (including allergy to drug or its excipients) 9. Intake of drugs within 1 month or less than 10 half-lives of the respective drug prior to first study drug administration 10. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial 11. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily) 12. Alcohol abuse (average consumption of more than 20 g/day in women and 30 g/day in men) 13. Drug abuse 14. Blood donation (more than 100 mL within 4 weeks before Day 1 of Visit 2) 15. Any laboratory value outside the reference range of clinical relevance 16. Inability to comply with dietary regimen of trial site For female subjects of childbearing potential only: 17. Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion 18. No adequate contraception during the study and until 1 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, hormonal intrauterine device, sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilization (including hysterectomy). Women who did not have a vasectomised partner, were not sexually abstinent or surgically sterile were asked to use an additional barrier method (e.g. condom). 19. Lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax (maximum measured concentration of the analyte in plasma) | up to 72 hours |
| AUC0-∞ (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity) | up to 72 hours |
| AUC0-72 (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 h) | up to 72 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| %AUCtz-∞ (percentage of AUCtz-∞ obtained by extrapolation) | up to 72 hours | — |
| AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2) | up to 72 hours | — |
| tmax (time from dosing until maximum concentration of the analyte in plasma) | up to 72 hours | — |
| λz (terminal elimination rate constant in plasma) | up to 72 hours | — |
| t1/2 (terminal half-life of the analyte in plasma) | up to 72 hours | — |
| MRTpo (mean residence time of the analyte in the body after peroral administration) | up to 72 hours | — |
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) | up to 72 hours | — |
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) | up to 72 hours | — |
| Number of subjects with clinically significant findings in vital signs | up to 7 days after last drug administration | blood pressure, pulse rate |
| Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG) | up to 7 days after last drug administration | — |
| Number of subjects with clinically significant findings in laboratory tests | up to 7 days after last drug administration | — |
| Number of subjects with adverse events | up to 7 days after last drug administration | — |
| Assessment of tolerability by investigator on a 4-point scale | up to 7 days after last drug administration | — |
| AUC0-∞ (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity) | up to 72 hours | — |
| 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) | up to 72 hours | — |
Outcome results
None listed