Healthy
Conditions
Brief summary
The objective of the study is to investigate the drug-drug interaction potential between BI 10773 and simvastatin.
Interventions
DRUGBI 10773
Medium dose oral administration
DRUGsimvastatin
Medium dose oral administration
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
\- healthy male and female subjects
Exclusion criteria
\- Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 0 hours (h), 20minutes (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. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values. |
| Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞) | 0 hours (h), 20minutes (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 the analyte in plasma over the time interval from 0 extrapolated to infinity. Simvastatin acid is an active metabolite of simvastatin. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values. |
| Empa: Maximum Measured Concentration (Cmax) | 0 hours (h), 20minutes (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 the analyte in plasma, per period. The geometric mean and geometric coefficient of variation (gCV) are adjusted values |
| Simvastatin: Maximum Measured Concentration (Cmax) | 0 hours (h), 20minutes (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 the analyte in plasma, per period. The geometric mean and geometric coefficient of variation (gCV) are adjusted values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 0 hours (h), 20minutes (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 the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point. The geometric mean and geometric coefficient of variation (gCV) are adjusted values. |
| Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 0 hours (h), 20minutes (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 the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point. The geometric mean and geometric coefficient of variation (gCV) are adjusted values. |
Countries
Germany
Participant flow
Pre-assignment details
This was a randomised, open label, 3 period crossover study. Treatment periods were separated by a washout period of at least 7 days.
Participants by arm
| Arm | Count |
|---|---|
| Study Overall This was a randomised, 3-period, crossover trial. The trial was open label. The three treatments were separated by a washout period of at least 7 days. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Third Intervention (3 Days) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Study Overall |
|---|---|
| Age, Continuous | 35.9 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 18 | 4 / 17 | 5 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 18 |
Outcome results
Primary
Empa: 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. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values.
Time frame: 0 hours (h), 20minutes (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: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Alone | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 5571.70 nmol*h/L | Geometric Coefficient of Variation 5.4 |
| Empa Plus Sim | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 5685.69 nmol*h/L | Geometric Coefficient of Variation 5.4 |
Comparison: Considered characteristic is empa plus simvastatin divided by empa alone90% CI: [98.9, 105.29]ANOVA
Primary
Empa: Maximum Measured Concentration (Cmax)
Maximum measured concentration of the analyte in plasma, per period. The geometric mean and geometric coefficient of variation (gCV) are adjusted values
Time frame: 0 hours (h), 20minutes (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: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Alone | Empa: Maximum Measured Concentration (Cmax) | 774.06 nmol/L | Geometric Coefficient of Variation 21.1 |
| Empa Plus Sim | Empa: Maximum Measured Concentration (Cmax) | 847.49 nmol/L | Geometric Coefficient of Variation 21.1 |
Comparison: Considered characteristic is empa plus simvastatin divided by empa alone90% CI: [96.91, 123.69]ANOVA
Primary
Simvastatin: 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. Simvastatin acid is an active metabolite of simvastatin. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values.
Time frame: 0 hours (h), 20minutes (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: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Empa Alone | Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞) | AUC of simvastatin | 33.51 ng*h/mL | Geometric Coefficient of Variation 40.4 |
| Empa Alone | Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞) | AUC of simvastatin acid | 16.83 ng*h/mL | Geometric Coefficient of Variation 25.5 |
| Empa Plus Sim | Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞) | AUC of simvastatin | 33.93 ng*h/mL | Geometric Coefficient of Variation 40.4 |
| Empa Plus Sim | Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞) | AUC of simvastatin acid | 17.65 ng*h/mL | Geometric Coefficient of Variation 25.5 |
Comparison: AUC of simvastatin~Considered characteristic is empa plus simvastatin divided by simvastatin alone90% CI: [80.06, 128.07]ANOVA
Comparison: AUC of simvastatin acid~Considered characteristic is empa plus simvastatin divided by simvastatin alone.90% CI: [90.09, 122.07]ANOVA
Primary
Simvastatin: Maximum Measured Concentration (Cmax)
Maximum measured concentration of the analyte in plasma, per period. The geometric mean and geometric coefficient of variation (gCV) are adjusted values.
Time frame: 0 hours (h), 20minutes (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: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Empa Alone | Simvastatin: Maximum Measured Concentration (Cmax) | Cmax of simvastatin | 7.88 ng/mL | Geometric Coefficient of Variation 41.7 |
| Empa Alone | Simvastatin: Maximum Measured Concentration (Cmax) | Cmax of simvastatin acid | 1.51 ng/mL | Geometric Coefficient of Variation 22.7 |
| Empa Plus Sim | Simvastatin: Maximum Measured Concentration (Cmax) | Cmax of simvastatin | 7.65 ng/mL | Geometric Coefficient of Variation 41.7 |
| Empa Plus Sim | Simvastatin: Maximum Measured Concentration (Cmax) | Cmax of simvastatin acid | 1.47 ng/mL | Geometric Coefficient of Variation 22.7 |
Comparison: Cmax of simvastatin.~Considered characteristic is empa plus simvastatin divided by simvastatin alone.90% CI: [76.3, 123.77]ANOVA
Comparison: Cmax of simvastatin acid.~Considered characteristic is empa plus simvastatin divided by simvastatin alone.90% CI: [84.9, 111.44]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 time of the last quantifiable data point. The geometric mean and geometric coefficient of variation (gCV) are adjusted values.
Time frame: 0 hours (h), 20minutes (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: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Alone | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 5481.31 nmol*h/L | Geometric Coefficient of Variation 5.8 |
| Empa Plus Sim | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 5619.60 nmol*h/L | Geometric Coefficient of Variation 5.8 |
Comparison: Considered characteristic is empa plus simvastatin divided by empa alone.90% CI: [99.1, 106.06]ANOVA
Secondary
Simvastatin: 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 time of the last quantifiable data point. The geometric mean and geometric coefficient of variation (gCV) are adjusted values.
Time frame: 0 hours (h), 20minutes (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: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Empa Alone | Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC of simvastatin | 31.82 ng*h/mL | Geometric Coefficient of Variation 41.7 |
| Empa Alone | Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC of simvastatin acid | 14.86 ng*h/mL | Geometric Coefficient of Variation 24.8 |
| Empa Plus Sim | Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC of simvastatin | 32.57 ng*h/mL | Geometric Coefficient of Variation 41.7 |
| Empa Plus Sim | Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC of simvastatin acid | 16.53 ng*h/mL | Geometric Coefficient of Variation 24.8 |
Comparison: AUC of simvastatin.~Considered characteristic is empa plus simvastatin divided by simvastatin alone.90% CI: [80.39, 130.29]ANOVA
Comparison: AUC of simvastatin acid.~Considered characteristic is empa plus simvastatin divided by simvastatin alone.90% CI: [95.93, 129.02]ANOVA