Bioequivalence of a 2.5 mg Linagliptin / 500 mg Metformin Fixed Dose Combination Tablet Compared With Single Linagliptin 2.5 mg and Metformin 500 mg Tablets Administered Together in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Study to demonstrate bioequivalence of a 2.5 mg linagliptin / 500 mg metformin fixed dose combination (FDC) tablet compared to single tablets of linagliptin 2.5 mg and metformin 500 mg administered together

Official Title
-----------------
Bioequivalence of a 2.5 mg Linagliptin / 500 mg Metformin Fixed Dose Combination Tablet Compared With Single Linagliptin 2.5 mg and Metformin 500 mg Tablets Administered Together in Healthy Male and Female Volunteers (an Open-label, Randomised, Single-dose, Two-way Crossover, Phase I Trial)

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Linagliptin/Metformin FDC
* Drug: Linagliptin
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Electrocardiogram (ECG), clinical laboratory tests Age 21 to 50 years (inclusive) Body mass index (BMI) 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) 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 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 Participation 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 women and 30 g/day in men) Drug abuse Blood donation (more than 100 mL within 4 weeks before Day 1 of Visit 2) Any laboratory value outside the reference range of clinical relevance Inability to comply with dietary regimen of trial site For female subjects of childbearing potential only: Positive pregnancy test, pregnancy or planning 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, or surgical sterilization (including hysterectomy). Lactation

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A (FDC)<br> | Drug: Linagliptin/Metformin FDC<br> <br> |
| Active Comparator: Treatment B (single agents)<br> | Drug: Linagliptin<br> <br> Drug: Metformin<br> <br> |

What is the study measuring?
-----------------
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 | 
| 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 | 

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 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 | 
| %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 to the 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 | blood pressure, pulse rate | up to 7 days after drug administration | 
| Number of subjects with clinically significant findings in 12-lead electrocardiogram (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 investigator on a 4-point scale |  | up to 7 days after drug administration |