Healthy
Conditions
Brief summary
The primary objective of this trial is to establish bioequivalence of two FDC tablets and the single tablets when administered together after a high fat high caloric meal.
Interventions
DRUGEmpagliflozin
empagliflozin tablets and metformin tablet
fixed dose combination tablet (low)
DRUGMetformin
empagliflozin tablets and metformin tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Healthy male and female subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empa: Maximum Measured Concentration (Cmax) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Metformin: Maximum Measured Concentration (Cmax) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Countries
Germany
Participant flow
Pre-assignment details
This was an open-label, randomized, 4-way crossover trial. 36 patients were randomised to one of 4 treatment sequences and treated. Each treatment period consisted of a single dose of medication followed by 72 hours of pharmacokinetic sampling, with a washout of at least 7 days between treatment periods.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Total number of patients randomised and treated in the study. This was an open-label, randomized, 4-way crossover trial. 36 patients were randomised to one of 4 treatment sequences and treated. Each treatment period consisted of a single dose of medication followed by 72hours of pharmacokinetic sampling, with a washout of at least 7 days between treatment periods. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Washout Period 2 (7 Days) | Adverse Event | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 33.6 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 35 | 13 / 36 | 14 / 34 | 9 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 | 0 / 34 | 0 / 35 |
Outcome results
Primary
Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 12.5mg Fixed-dose | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 2560 nmol*h/L | Geometric Coefficient of Variation 25.5 |
| Empa 12.5mg Free Dose | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 2530 nmol*h/L | Geometric Coefficient of Variation 29.5 |
| Empa 5mg Fixed-dose | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 986 nmol*h/L | Geometric Coefficient of Variation 26.9 |
| Empa 5mg Free Dose | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 968 nmol*h/L | Geometric Coefficient of Variation 23.9 |
90% CI: [96.89, 105.93]ANOVA
90% CI: [97.4, 103.29]ANOVA
Primary
Empa: Maximum Measured Concentration (Cmax)
Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 12.5mg Fixed-dose | Empa: Maximum Measured Concentration (Cmax) | 266 nmol/L | Geometric Coefficient of Variation 20.3 |
| Empa 12.5mg Free Dose | Empa: Maximum Measured Concentration (Cmax) | 258 nmol/L | Geometric Coefficient of Variation 21.3 |
| Empa 5mg Fixed-dose | Empa: Maximum Measured Concentration (Cmax) | 103 nmol/L | Geometric Coefficient of Variation 22.1 |
| Empa 5mg Free Dose | Empa: Maximum Measured Concentration (Cmax) | 101 nmol/L | Geometric Coefficient of Variation 24.4 |
90% CI: [98.75, 106.81]ANOVA
90% CI: [95.94, 106.27]ANOVA
Primary
Metformin: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 12.5mg Fixed-dose | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 8640 ng*h/mL | Geometric Coefficient of Variation 18 |
| Empa 12.5mg Free Dose | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 8450 ng*h/mL | Geometric Coefficient of Variation 24.4 |
| Empa 5mg Fixed-dose | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 8520 ng*h/mL | Geometric Coefficient of Variation 23.8 |
| Empa 5mg Free Dose | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 8560 ng*h/mL | Geometric Coefficient of Variation 25.8 |
90% CI: [97.94, 105.41]ANOVA
90% CI: [94.24, 103.08]ANOVA
Primary
Metformin: Maximum Measured Concentration (Cmax)
Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 12.5mg Fixed-dose | Metformin: Maximum Measured Concentration (Cmax) | 1080 ng/mL | Geometric Coefficient of Variation 16.4 |
| Empa 12.5mg Free Dose | Metformin: Maximum Measured Concentration (Cmax) | 1080 ng/mL | Geometric Coefficient of Variation 19.6 |
| Empa 5mg Fixed-dose | Metformin: Maximum Measured Concentration (Cmax) | 1090 ng/mL | Geometric Coefficient of Variation 16.5 |
| Empa 5mg Free Dose | Metformin: Maximum Measured Concentration (Cmax) | 1100 ng/mL | Geometric Coefficient of Variation 17.5 |
90% CI: [95.39, 104.09]ANOVA
90% CI: [93.82, 102.15]ANOVA
Secondary
Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 12.5mg Fixed-dose | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 2520 nmol*h/L | Geometric Coefficient of Variation 25.1 |
| Empa 12.5mg Free Dose | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 2490 nmol*h/L | Geometric Coefficient of Variation 29.3 |
| Empa 5mg Fixed-dose | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 963 nmol*h/L | Geometric Coefficient of Variation 27.1 |
| Empa 5mg Free Dose | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 946 nmol*h/L | Geometric Coefficient of Variation 24.2 |
90% CI: [96.89, 105.71]ANOVA
90% CI: [97.41, 103.3]ANOVA
Secondary
Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the Measured values shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 12.5mg Fixed-dose | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 8370 ng*h/mL | Geometric Coefficient of Variation 18.1 |
| Empa 12.5mg Free Dose | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 8190 ng*h/mL | Geometric Coefficient of Variation 24.1 |
| Empa 5mg Fixed-dose | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 8280 ng*h/mL | Geometric Coefficient of Variation 23.2 |
| Empa 5mg Free Dose | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 8320 ng*h/mL | Geometric Coefficient of Variation 25.2 |
90% CI: [97.95, 105.21]ANOVA
90% CI: [94.5, 102.81]ANOVA