Healthy
Conditions
Brief summary
The objective of the study is to investigate the relative bioavailability of digoxin after concomitant multiple oral administration of BI 10773 and a single dose of digoxin in comparison to digoxin given alone to healthy male and female subjects.
Interventions
DRUGDigoxin plus BI 10773
Digoxin 0.5 mg as single dose, BI 10773 medium dose once daily
DRUGDigoxin
Digoxin 0.5 mg as single dose
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 |
|---|---|---|
| Digoxin: Area Under the Curve 0 to Infinity (AUC0-∞) | 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose | Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity. |
| Digoxin: Maximum Measured Concentration (Cmax) | 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose | Maximum measured concentration of digoxin, per period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Digoxin: Area Under the Curve 0 to Last Quantifiable Data Point (AUC0-tz) | 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose | Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to the time of the last quantifiable data point. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Total This was a randomised, two-period, cross-over trial, the two treatments administered were
* A single dose of digoxin 0.5 mg on day 1
* Empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5
Between treatment periods there was a washout period of at least 14 days. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Study Total |
|---|---|
| Age, Continuous | 34.3 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Digoxin: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose
Population: Pharmacokinetic (PK) set comprised all evaluable subjects who took at least 1 dose of study medication with at least 1 observation for at least 1 primary PK endpoint without any important protocol violations relevant to the PK evaluation. One subject was excluded from the PK set because the pre-dose plasma concentration of digoxin was \>5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Alone | Digoxin: Area Under the Curve 0 to Infinity (AUC0-∞) | 37.8 ng-h/mL | Geometric Coefficient of Variation 23.2 |
| Digoxin and Empa | Digoxin: Area Under the Curve 0 to Infinity (AUC0-∞) | 39.9 ng-h/mL | Geometric Coefficient of Variation 26 |
Primary
Digoxin: Maximum Measured Concentration (Cmax)
Maximum measured concentration of digoxin, per period.
Time frame: 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose
Population: Pharmacokinetic (PK) set comprised all evaluable subjects who took at least 1 dose of study medication with at least 1 observation for at least 1 primary PK endpoint without any important protocol violations relevant to the PK evaluation. One subject was excluded from the PK set because the pre-dose plasma concentration of digoxin was \>5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Alone | Digoxin: Maximum Measured Concentration (Cmax) | 1.97 ng/mL | Geometric Coefficient of Variation 43.3 |
| Digoxin and Empa | Digoxin: Maximum Measured Concentration (Cmax) | 2.25 ng/mL | Geometric Coefficient of Variation 33.8 |
Secondary
Digoxin: Area Under the Curve 0 to Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to the time of the last quantifiable data point.
Time frame: 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose
Population: Pharmacokinetic (PK) set comprised all evaluable subjects who took at least 1 dose of study medication with at least 1 observation for at least 1 primary PK endpoint without any important protocol violations relevant to the PK evaluation. One subject was excluded from the PK set because the pre-dose plasma concentration of digoxin was \>5% of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Alone | Digoxin: Area Under the Curve 0 to Last Quantifiable Data Point (AUC0-tz) | 24.8 ng*h/mL | Geometric Coefficient of Variation 24.8 |
| Digoxin and Empa | Digoxin: Area Under the Curve 0 to Last Quantifiable Data Point (AUC0-tz) | 28.4 ng*h/mL | Geometric Coefficient of Variation 24.3 |