Relative Bioavailability of a Linagliptin+Metformin Fixed Dose Combination Tablet Administered With and Without Food to Healthy Male and Female Subjects

Study Overview
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Brief Summary
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Study to investigate the effect of food on the relative bioavailability of a 2.5 mg linagliptin+1000 mg metformin fixed dose combination (FDC) tablet

Official Title
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Relative Bioavailability of a 2.5 mg Linagliptin / 1000 mg Metformin Fixed Dose Combination Tablet Administered With and Without Food to Healthy Male and Female Subjects in an Open, Randomised, Single-dose, Two-way Crossover, Phase I Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: Linagliptin/metformin FDC
* Other: high-fat, high caloric meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females 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 Age 18 to 55 years (inclusive) Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) 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: Any finding of the medical examination (including BP, PR, and ECG) which deviated 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), psychiatric disorders, or neurological disorders History of relevant orthostatic hypotension, fainting spells, or blackouts Chronic or relevant acute infections History of relevant allergy or hypersensitivity (including allergy to drug or its excipients) Intake of drugs within 1 month or less than 10 half-lives of the respective drug prior to first study drug administration Participated in another trial with an investigational drug within 2 months prior to administration or during the trial Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily) Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males) Drug abuse Blood donation (more than 100 mL within 4 weeks prior to administration) Any laboratory value outside the reference range that was of clinical relevance Inability to comply with dietary regimen of trial site For female subjects of childbearing potential only: Positive pregnancy test, pregnancy, or had planned to become pregnant during the study or within 2 months after study completion 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 were not surgically sterile were asked to use an additional barrier method (e.g. condom) Lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Linagliptin/metformin fed<br> | Drug: Linagliptin/metformin FDC<br> <br> Other: high-fat, high caloric meal<br> <br> |
| Active Comparator: Linagliptin/metformin fasted<br> | Drug: Linagliptin/metformin FDC<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 after drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 72 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of metformin in plasma over the time interval from 0 h extrapolated to infinity) |  | up to 72 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 h extrapolated to infinity) |  | up to 72 hours after drug administration | 
| 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 after drug administration | 
| AUCt1-t2 (area under the concentration time curve of the analyte in plasma over the time interval t1 to t2) |  | up to 72 hours after drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | up to 72 hours after drug administration | 
| λz (terminal elimination rate constant in plasma) |  | up to 72 hours after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 72 hours after drug administration | 
| MRTpo (mean residence time of the analyte in the body after oral administration) |  | up to 72 hours after drug administration | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | up to 72 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 72 hours after drug administration | 
| Number of subjects with clinically significant findings in vital signs | blood pressure, pulse rate | up to 7 days after drug administration | 
| Number of subjects with clinically significant findings in ECG |  | up to 7 days after drug administration | 
| Number of subjects with clinically significant findings in laboratory tests |  | up to 7 days after drug administration | 
| Number of subjects with adverse events |  | up to 7 days after drug administration | 
| Assessment of tolerability by the investigator on a 4-point scale |  | up to 7 days after drug administration |