Healthy
Conditions
Brief summary
The objectives of the trial are to investigate the effect of concurrent administration of rifampicin and probenecid on the pharmacokinetics of empagliflozin.
Interventions
DRUGProbenecid
Probenecid
DRUGRifampicin
Rifampicin
DRUGEmpagliflozin
BI Drug
BI Drug
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 |
|---|---|---|
| Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) | 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose | Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. |
| Total Empa: Maximum Measured Concentration (Cmax) | 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose | Maximum measured concentration of total empa in plasma, per period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose | Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to the time of last the quantifiable data point. |
Countries
Germany
Participant flow
Pre-assignment details
This was a randomised, 3-way crossover trial. 18 patients were randomised to one of six treatment sequences and treated. It was an open label trial in which each treatment period lasted 4 days with a washout period of at least 7 days between each.
Participants by arm
| Arm | Count |
|---|---|
| Study Overall This was a randomised, 3-way crossover trial. 18 patients were randomised to one of six treatment sequences and treated. It was an open label trial in which each treatment period lasted 4 days with a washout period of at least 7 days between each. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Study Overall |
|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 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 | 7 / 18 | 9 / 18 | 6 / 16 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 16 |
Outcome results
Primary
Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Population: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Alone | Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) | 2240 nmol*h/L | Geometric Coefficient of Variation 28.1 |
| Empa + Rifampicin | Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) | 3020 nmol*h/L | Geometric Coefficient of Variation 28.2 |
| Empa + Probenecid | Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) | 3400 nmol*h/L | Geometric Coefficient of Variation 28.7 |
90% CI: [129.58, 141.06]ANOVA
90% CI: [146.41, 160.88]ANOVA
Primary
Total Empa: Maximum Measured Concentration (Cmax)
Maximum measured concentration of total empa in plasma, per period.
Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Population: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Alone | Total Empa: Maximum Measured Concentration (Cmax) | 301 nmol/L | Geometric Coefficient of Variation 31.6 |
| Empa + Rifampicin | Total Empa: Maximum Measured Concentration (Cmax) | 527 nmol/L | Geometric Coefficient of Variation 27.5 |
| Empa + Probenecid | Total Empa: Maximum Measured Concentration (Cmax) | 373 nmol/L | Geometric Coefficient of Variation 30.9 |
90% CI: [113.67, 138.78]ANOVA
90% CI: [160.14, 191.56]ANOVA
Secondary
Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to the time of last the quantifiable data point.
Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Population: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa Alone | Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 2200 nmol*h/L | Geometric Coefficient of Variation 28.6 |
| Empa + Rifampicin | Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 3000 nmol*h/L | Geometric Coefficient of Variation 28.4 |
| Empa + Probenecid | Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 3350 nmol*h/L | Geometric Coefficient of Variation 29.1 |
90% CI: [130.61, 142.48]ANOVA
90% CI: [146.5, 161.06]ANOVA