Healthy
Conditions
Brief summary
The primary objective of the current study is to investigate the relative bioavailability of BI 10773 / linagliptin fixed dose combination tablet (formulation A1, Treatment A, Test) compared to BI 10773 given in free combination with linagliptin (Treatment B, Reference), both in the fasting state. All 42 subjects entered are planned to be included in this comparison. The secondary objective is to investigate the relative bioavailability of BI 10773 / linagliptin fixed dose combination tablet after administration of a standardised high fat, high caloric meal (formulation A1, Treatment C, Test) compared to BI 10773 / linagliptin fixed dose combination in the fasting state (formulation A1,Treatment A, Reference). Of the 42 subjects entered 18 subjects are planned to be included in this comparison. An additional objective is to investigate the relative bioavailability of a second formulation of the fixed dose combination tablet of BI 10773 / linagliptin (formulation A3,Treatment D, Test) compared to BI 10773 / linagliptin fixed dose combination tablet (formulation A1,Treatment A, Reference). Of the 42 subjects entered 24 subjects are planned to be included in this comparison.
Interventions
DRUGBI 10773/linagliptin
medium single dose of BI 10773/linagliptin FDC (Formulation A1)
DRUGBI 10773/linagliptin SID
medium single dose of mono components BI 10773/linagliptin
DRUGBI 10773/linagliptin FDC
medium single dose of BI 10773/linagliptin FDC (Formulation A1) after high fat, high caloric meal
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
healthy male and female subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Linagliptin Formulation Comparison: Area Under the Curve 0 to 72 Hours (AUC0-72) | 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, 72h after drug administration | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin: 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, 72h after drug administration | Maximum measured concentration of empagliflozin (empa) in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin: 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, 72h after drug administration | Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin Fed vs Fasted: 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, 72h after drug administration | Maximum measured concentration of empagliflozin (empa) in plasma, comparing fed with fasted. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin Fed vs Fasted: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (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, 72h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin Fed vs Fasted: 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, 72h after drug administration | Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin Fed vs Fasted: Area Under the Curve 0 to 72 Hours (AUC0-72) | 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, 72h after drug administration | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin Formulation Comparison: 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, 72h after drug administration | Maximum measured concentration of empagliflozin (empa) in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin Formulation Comparison: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (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, 72h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin Formulation Comparison: 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, 72h after drug administration | Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (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, 72h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin: Area Under the Curve 0 to 72 Hours (AUC0-72) | 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, 72h after drug administration | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 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, 72h after drug administration | Time from last dosing to the maximum measured concentration of linagliptin in plasma |
| Empagliflozin: 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, 72h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin: 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, 72h after drug administration | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin Fed vs Fasted: 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, 72h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin Fed vs Fasted: 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, 72h after drug administration | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Empagliflozin Formulation Comparison: 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, 72h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Linagliptin Formulation Comparison: 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, 72h after drug administration | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator | Drug administration until next treatment period/end-of-study examination, up to 36 days | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event was until the end-of-study examination. |
| Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 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, 72h after drug administration | Time from last dosing to the maximum measured concentration of empagliflozin (empa) in plasma. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Overall A randomised, open label, three period, crossover trial. Each subject was to receive 3 of 4 possible treatments. The treatments were
* Empagliflozin plus linagliptin fixed dose combination (FDC) A1 (fasted)
* Empagliflozin plus linagliptin, individual tablets (fasted)
* Empagliflozin plus linagliptin FDC A1 (fed)
* Empagliflozin plus linagliptin FDC A3 (fasted)
Drug administrations were separated by a washout period of at least 35 days.
A total of 42 subjects were entered into the study, all subjects were allocated to the FDC A1 (fasted) and individual tablet treatments as this was the primary objective of the study. Along with this 18 of the subjects were allocated to receive the FDC A1 (fed) treatment and other 24 subjects to the FDC A3 treatment. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Study Overall |
|---|---|
| Age, Continuous | 40.3 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 17 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 | 8 / 42 | 5 / 41 | 6 / 18 | 4 / 24 |
| serious Total, serious adverse events | 0 / 42 | 0 / 41 | 0 / 18 | 0 / 24 |
Outcome results
Primary
Empagliflozin: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz)
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | 5990 nmol*h/L | Geometric Coefficient of Variation 21 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | 5720 nmol*h/L | Geometric Coefficient of Variation 20.8 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [102.07, 107.8]ANOVA
Primary
Empagliflozin Fed vs Fasted: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz)
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin Fed vs Fasted: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | 6330 nmol*h/L | Geometric Coefficient of Variation 16.4 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin Fed vs Fasted: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | 5400 nmol*h/L | Geometric Coefficient of Variation 16.3 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [80.77, 90.14]ANOVA
Primary
Empagliflozin Fed vs Fasted: Maximum Measured Concentration (Cmax)
Maximum measured concentration of empagliflozin (empa) in plasma, comparing fed with fasted. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin Fed vs Fasted: Maximum Measured Concentration (Cmax) | 949 nmol/L | Geometric Coefficient of Variation 23.7 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin Fed vs Fasted: Maximum Measured Concentration (Cmax) | 583 nmol/L | Geometric Coefficient of Variation 21.7 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [54.1, 69.71]ANOVA
Primary
Empagliflozin Formulation Comparison: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz)
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin Formulation Comparison: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | 5740 nmol*h/L | Geometric Coefficient of Variation 23.3 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin Formulation Comparison: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | 5490 nmol*h/L | Geometric Coefficient of Variation 21.1 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [91.17, 100.43]ANOVA
Primary
Empagliflozin Formulation Comparison: Maximum Measured Concentration (Cmax)
Maximum measured concentration of empagliflozin (empa) in plasma. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin Formulation Comparison: Maximum Measured Concentration (Cmax) | 802 nmol/L | Geometric Coefficient of Variation 27 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin Formulation Comparison: Maximum Measured Concentration (Cmax) | 787 nmol/L | Geometric Coefficient of Variation 25.2 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [91.95, 104.53]ANOVA
Primary
Empagliflozin: Maximum Measured Concentration (Cmax)
Maximum measured concentration of empagliflozin (empa) in plasma. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin: Maximum Measured Concentration (Cmax) | 862 nmol/L | Geometric Coefficient of Variation 26.8 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin: Maximum Measured Concentration (Cmax) | 803 nmol/L | Geometric Coefficient of Variation 24.9 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [101.7, 114.02]ANOVA
Primary
Linagliptin: Area Under the Curve 0 to 72 Hours (AUC0-72)
Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin: Area Under the Curve 0 to 72 Hours (AUC0-72) | 264 nmol*h/L | Geometric Coefficient of Variation 22.1 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin: Area Under the Curve 0 to 72 Hours (AUC0-72) | 250 nmol*h/L | Geometric Coefficient of Variation 22.1 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [99.97, 110.09]ANOVA
Primary
Linagliptin Fed vs Fasted: Area Under the Curve 0 to 72 Hours (AUC0-72)
Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin Fed vs Fasted: Area Under the Curve 0 to 72 Hours (AUC0-72) | 275 nmol*h/L | Geometric Coefficient of Variation 21.7 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin Fed vs Fasted: Area Under the Curve 0 to 72 Hours (AUC0-72) | 250 nmol*h/L | Geometric Coefficient of Variation 19.2 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [84.24, 98.19]ANOVA
Primary
Linagliptin Fed vs Fasted: Maximum Measured Concentration (Cmax)
Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin Fed vs Fasted: Maximum Measured Concentration (Cmax) | 8.97 nmol/L | Geometric Coefficient of Variation 40 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin Fed vs Fasted: Maximum Measured Concentration (Cmax) | 6.14 nmol/L | Geometric Coefficient of Variation 17 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [58.59, 80.03]ANOVA
Primary
Linagliptin Formulation Comparison: Area Under the Curve 0 to 72 Hours (AUC0-72)
Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin Formulation Comparison: Area Under the Curve 0 to 72 Hours (AUC0-72) | 256 nmol*h/L | Geometric Coefficient of Variation 22.4 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin Formulation Comparison: Area Under the Curve 0 to 72 Hours (AUC0-72) | 247 nmol*h/L | Geometric Coefficient of Variation 26.3 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [89.78, 103.42]ANOVA
Primary
Linagliptin Formulation Comparison: Maximum Measured Concentration (Cmax)
Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin Formulation Comparison: Maximum Measured Concentration (Cmax) | 7.65 nmol/L | Geometric Coefficient of Variation 32.7 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin Formulation Comparison: Maximum Measured Concentration (Cmax) | 7.93 nmol/L | Geometric Coefficient of Variation 33.5 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [92.93, 115.74]ANOVA
Primary
Linagliptin: Maximum Measured Concentration (Cmax)
Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin: Maximum Measured Concentration (Cmax) | 8.19 nmol/L | Geometric Coefficient of Variation 36.4 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin: Maximum Measured Concentration (Cmax) | 7.49 nmol/L | Geometric Coefficient of Variation 31 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [99.55, 120.83]ANOVA
Secondary
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event was until the end-of-study examination.
Time frame: Drug administration until next treatment period/end-of-study examination, up to 36 days
Population: Treated set (TS) included all subjects who were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator | 0 participants |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator | 0 participants |
| Empa Plus Linagliptin FDC A1 (Fed) | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator | 0 participants |
| Empa Plus Linagliptin FDC A3 (Fasted) | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator | 0 participants |
Secondary
Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) | 6060 nmol*h/L | Geometric Coefficient of Variation 20.7 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) | 5800 nmol*h/L | Geometric Coefficient of Variation 20.9 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [102.02, 107.61]ANOVA
Secondary
Empagliflozin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) | 6410 nmol*h/L | Geometric Coefficient of Variation 16 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) | 5500 nmol*h/L | Geometric Coefficient of Variation 16.8 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [81.33, 90.64]ANOVA
Secondary
Empagliflozin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) | 5810 nmol*h/L | Geometric Coefficient of Variation 23.1 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) | 5560 nmol*h/L | Geometric Coefficient of Variation 20.8 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [91.19, 100.3]ANOVA
Secondary
Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax)
Time from last dosing to the maximum measured concentration of empagliflozin (empa) in plasma.
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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 1.50 hours |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 1.25 hours |
| Empa Plus Linagliptin FDC A1 (Fed) | Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 2.00 hours |
| Empa Plus Linagliptin FDC A3 (Fasted) | Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 1.50 hours |
Secondary
Linagliptin: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin: Area Under the Curve 0 to Infinity (AUC0-∞) | 435 nmol*h/L | Geometric Coefficient of Variation 26.5 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin: Area Under the Curve 0 to Infinity (AUC0-∞) | 410 nmol*h/L | Geometric Coefficient of Variation 29.8 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [97.23, 112.62]ANOVA
Secondary
Linagliptin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) | 453 nmol*h/L | Geometric Coefficient of Variation 24.2 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) | 421 nmol*h/L | Geometric Coefficient of Variation 19 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [85.07, 102.05]ANOVA
Secondary
Linagliptin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show 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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) | 423 nmol*h/L | Geometric Coefficient of Variation 28.3 |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) | 393 nmol*h/L | Geometric Coefficient of Variation 33.8 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [86.36, 100.09]ANOVA
Secondary
Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax)
Time from last dosing to the maximum measured concentration of linagliptin in plasma
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, 72h after drug administration
Population: Pharmacokinetic (PK) set: Included all subjects who were documented to have taken at least one dose of investigational treatment, who provided at least one observation for at least one primary endpoint without important protocol violations relevant to the PK evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Empa Plus Linagliptin FDC A1 (Fasted) | Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 1.50 hours |
| Empa Plus Linagliptin Individual Tablets (Fasted) | Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 1.75 hours |
| Empa Plus Linagliptin FDC A1 (Fed) | Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 2.25 hours |
| Empa Plus Linagliptin FDC A3 (Fasted) | Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | 1.50 hours |