Bioequivalence Study in Healthy Volunteers for Empagliflozin/Metformin Fixed Dose Combination Compared to Separate Tablets

Study Overview
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Brief Summary
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The trial is being conducted to establish the bioequivalence of emp/met (12.5mg/500mg) fixed dose combination tablets compared to tablets administered together in healthy male and female volunteers under fed conditions.

Official Title
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Bioequivalence of Empagliflozin/Metformin (12.5mg/500mg) Fixed Dose Combination Tablets Compared to Tablets Administered Together in Healthy Male and Female Volunteers Under Fed Conditions (an Open Label, Randomised, Single Dose, Two Period, Two Sequence Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Empagliflozin 2.5 mg
* Drug: Empagliflozin 10 mg
* Drug: Metformin 500 mg
* Drug: Empagliflozin/Metformin FDC


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males or females according to the investigator's assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests. Age 18 to 50 years (inclusive) 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 local legislation. Exclusion criteria: Any finding in the medical examination (Including blood pressure [BP], pulse rate [PR], or electrocardiogram [ECG]) deviating from normal and judged clinically relevant by the investigator. Any evidence of a concomitant disease judged clinically relevant by the investigator. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders. Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug(s) Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders. History of relevant orthostatic hypotension, fainting spells, or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to the trial medication or it's excipients) Intake of drugs with a long half-life (>24 hours) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication. Within 14 days prior to the administration of trial medication, use of drugs that might reasonably influence the results of the trial, based on current knowledge Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication. Smoker (has used tobacco or nicotine-containing products within 6 months prior to administration of trial medication) Inability to refrain from smoking on specified trial days Alcohol abuse (consumption of more than 20g/day in females and 30g/day in males or > 7 alcohol-containing drinks per week) Drug abuse or positive drug screen Blood donation (more than 100 ml wihtin 30 days prior to administration of trial medication or intended during the trial) Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial Inability to comply with dietary regimen of trial site Subject is assessed by the investigator as unsuitable for inclusion, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study. For female subjects: Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion. No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent, surgically sterile, or post menopausal will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide). Post-menopausal is defined as at least 1 year of spontaneous amenorrhea and deemed post menopausal by a physician based on screening clinical laboratory tests (follicle stimulating hormone and luteinizing hormone). Lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Dose Combination (FDC)<br>12.5 mg Empagliflozin / 500mg metformin fixed dose combination | Drug: Empagliflozin/Metformin FDC<br>* 12.5 mg Empagliflozin / 500 mg Metformin<br>|
| Active Comparator: Separate tablets<br>Empagliflozin and Metformin tablets | Drug: Empagliflozin 2.5 mg<br>* Empagliflozin 2.5 mg tablet<br>Drug: Empagliflozin 10 mg<br>* Empagliflozin 10 mg tablet<br>Drug: Metformin 500 mg<br>* Metformin 500 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-tz) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) | AUC (0-tz) (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Cmax (Maximum Measured Concentration of Metformin in Plasma) | Cmax (maximum measured concentration of metformin in plasma) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-infinity) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | AUC (0-infinity) (Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |