This Study in Healthy People Tests Whether Taking a Low Strength of Empagliflozin, Linagliptin, and Metformin Together in 1 Pill is the Same as Taking Them in Separate Pills

Study Overview
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Brief Summary
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The primary objective of this trial is to establish the bioequivalence of two empagliflozin/linagliptin/metformin extended release (XR) fixed dose combination (FDC) tablets (Test, T) compared with the same doses of the individual components given in separate tablets (Reference, R) when administered together after a high-fat, high-calorie meal. The assessment of safety and tolerability will be the secondary objective of this trial.

Official Title
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Bioequivalence of a Low Strength Fixed Dose Combination Tablet of Empagliflozin/Linagliptin/Metformin Extended Release Compared to the Free Combination of Empagliflozin, Linagliptin, and Metformin Extended Release Tablets Following Oral Administration in Healthy Male and Female Subjects (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, Metformin HCl, Linagliptin (fixed dose combination)
* Drug: Empagliflozin
* Drug: Linagliptin
* Drug: Metformin HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests Age of 18 to 55 years (incl.) Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation Female subjects of childbearing potential willing to use adequate contraception. Further inclusion criteria apply Exclusion criteria: Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm) Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair) Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders Further exclusion criteria apply

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: Test treatment (T)<br>Low strength empagliflozin/linagliptin/metformin XR fixed dose combination tablet | Drug: Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination)<br>* single dose<br>* Other names: TRIJARDY® XR;|
| Experimental: Reference treatment (R)<br>Single tablets of empagliflozin + linagliptin + metformin XR | Drug: Empagliflozin<br>* single dose<br>Drug: Linagliptin<br>* single dose<br>Drug: Metformin HCl<br>* single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC0-tz, Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 to the last quantifiable data point is presented. Standard error (SE) is a geometric SE. | Pharmacokinetic (PK) samples were collected 1:30 hours:minutes (h:m) pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC0-tz, Area under the concentration-time curve of the metformin in plasma over the time interval from 0 to the last quantifiable data point is presented. Standard error (SE) is a geometric SE. | Pharmacokinetic (PK) samples were collected 1:30 hours:minutes (h:m) pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (h) (AUC0-72) | AUC0-72, area under the concentration-time curve of the linagliptin in plasma over the time interval from 0 to 72 h is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax) | Cmax, maximum measured concentration of the empagliflozin in plasma is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Maximum Measured Concentration of the Linagliptin in Plasma (Cmax) | Cmax, maximum measured concentration of the linagliptin in plasma is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Maximum Measured Concentration of the Metformin in Plasma (Cmax) | Cmax, maximum measured concentration of the metformin in plasma is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve of the Empagliflozin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Area Under the Concentration-time Curve of the Linagliptinin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of the linagliptin in plasma over the time interval from 0 extrapolated to infinity is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Area Under the Concentration-time Curve of the Metformin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity is presented. SE is a geometric SE. | PK samples were collected 1:30 h:m pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 h:m after drug administration. | 
| Percentage of Patients With Drug-related Adverse Events (AEs) | Percentage of patients with investigator defined drug-related AEs are presented. | All adverse events (AEs) which occurred through the treatment phase and throughout the residual effect period (REP), up to 7 days. |