Healthy
Conditions
Brief summary
Investigation of food effect on the bioavailability of a 25 mg empagliflozin tablet and assessment of dose proportionality between 10 mg and 25 mg empagliflozin tablets under fasting conditions.
Interventions
DRUGEmpagliflozin
high dose of empagliflozin after overnight fasting for at least 10 h
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
1\. Healthy male and female subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve 0 to Infinity (AUC0-∞) | 1 hour (h) before study drug 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 empagliflozin (empa) in plasma over the time interval from 0 hours extrapolated to infinity (AUC0-∞). The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities. |
| Maximum Measured Concentration (Cmax) | 1 hour (h) before study drug 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 empagloflozin (empa) in plasma, per period. The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator. | Screening until end of trial, average of 45 days | Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry, haematology, urinanalysis and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events (AEs). Time frame for AE reporting includes the period of first drug administration until end of study. A more detailed definition of the used time frame and MedDRA Version can be found in the AE section. |
Countries
Germany
Participant flow
Pre-assignment details
This was a randomised 3 period crossover trial. 18 patients were randomised to one of six treatment sequences and treated. The trial was open label with washout periods of at least 7 days between treatments.
Participants by arm
| Arm | Count |
|---|---|
| Study Overall Total number of patients randomised and treated in the study. This was a randomised 3 period crossover trial. 18 patients were randomised to one of six treatment sequences and treated. The trial was open label with washout periods of at least 7 days between treatments. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Study Overall |
|---|---|
| Age, Continuous | 36.1 years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 9 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 | 2 / 18 | 2 / 18 | 4 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
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 hours extrapolated to infinity (AUC0-∞). The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities.
Time frame: 1 hour (h) before study drug 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: All treated subjects who provided at least one observation in the relevant treatment periods for at least one primary pharmacokinetic (PK) endpoint without a relevant protocol deviation and who had not experienced emesis before or at 2 times median tmax in at least one of the two relevant treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 25 mg Fasted | Area Under the Curve 0 to Infinity (AUC0-∞) | 5380 nmol*h/L | Geometric Coefficient of Variation 26 |
| Empa 25 mg Fed | Area Under the Curve 0 to Infinity (AUC0-∞) | 4520 nmol*h/L | Geometric Coefficient of Variation 24.8 |
| Empa 10 mg Fasted | Area Under the Curve 0 to Infinity (AUC0-∞) | 2280 nmol*h/L | Geometric Coefficient of Variation 27 |
90% CI: [80.856, 87.344]ANOVA
95% CI: [0.8988, 0.9746]ANCOVA
Primary
Maximum Measured Concentration (Cmax)
Maximum measured concentration of empagloflozin (empa) in plasma, per period. The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities.
Time frame: 1 hour (h) before study drug 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: All treated subjects who provided at least one observation in the relevant treatment periods for at least one primary pharmacokinetic (PK) endpoint without a relevant protocol deviation and who had not experienced emesis before or at 2 times median tmax in at least one of the two relevant treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Empa 25 mg Fasted | Maximum Measured Concentration (Cmax) | 837 nmol/L | Geometric Coefficient of Variation 27.8 |
| Empa 25 mg Fed | Maximum Measured Concentration (Cmax) | 523 nmol/L | Geometric Coefficient of Variation 27.7 |
| Empa 10 mg Fasted | Maximum Measured Concentration (Cmax) | 365 nmol/L | Geometric Coefficient of Variation 27.7 |
90% CI: [56.736, 70.439]ANOVA
95% CI: [0.8011, 1.012]ANCOVA
Secondary
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator.
Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry, haematology, urinanalysis and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events (AEs). Time frame for AE reporting includes the period of first drug administration until end of study. A more detailed definition of the used time frame and MedDRA Version can be found in the AE section.
Time frame: Screening until end of trial, average of 45 days
Population: Treated Set(TS): TS includes all subjects who have taken at least 1 dose of trial medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empa 25 mg Fasted | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator. | 0 participants |
| Empa 25 mg Fed | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator. | 0 participants |
| Empa 10 mg Fasted | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator. | 0 participants |