Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto®.

Study Overview
=================
Brief Summary
-----------------
The objective of the current study is to demonstrate bioequivalence of two 2.5 mg linagliptin/500 mg metformin fixed dose combination tablets compared to the free combination of the linagliptin 5 mg and metformin 1000 mg in healthy male and female volunteers.

Official Title
-----------------
Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto® (Two Fixed Dose Combination Tablets of Linagliptin 2.5 mg and Metformin 500 mg) Compared With the Free Combination of Linagliptin 5 mg and Metformin 1000 mg Tablets Under Fasting Conditions.

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests (haematology, clinical chemistry and urinalysis). Age 18 to 45 years (incl.) Body mass index by Quetelet between 18.50 to 24.99 kg/m2 (incl.) Female subjects of childbearing potential who agree on using double-barrier contraception during the study. If a female is postmenopausal (no menses for at least 2 years) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) she will be exempt from the requirement. In case of using oral contraceptives, these should be withdrawn at least 2 months before the first drug dosing. Male subjects who agree on using effective contraception during the study (barrier contraceptive methods) Exclusion criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Any laboratory value outside the reference range that is of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Positive results of blood tests for infections (HIV, syphilis, hepatitis B or C) A positive urine drug screening test at screening and on admission to the trial site in each treatment period. A positive alcohol breath test at screening and on admission to the trial site in each treatment period. Surgery of the gastrointestinal tract (except appendectomy)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 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: Fixed dose combination<br>Linagliptin/Metformin | Drug: Linagliptin<br>* Fixed dose combination<br>Drug: Metformin<br>* Combination<br>|
| Experimental: Free combination<br>Linagliptin and Metformin | Drug: Metformin<br>* Free combination<br>Drug: Linagliptin<br>* Free combination<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours) | Linagliptin: AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Metformin: 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) | Metformin: 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) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Linagliptin: Cmax (Maximum Measured Concentration of the Analyte in Plasma) | Linagliptin: Cmax (maximum measured concentration of the analyte in plasma) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma) | Metformin: Cmax (maximum measured concentration of the analyte in plasma) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linagliptin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | Linagliptin: AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Metformin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | Metformin: AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Linagliptin: AUC 0-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) | Linagliptin: AUC 0-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) | 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |