Healthy
Conditions
Brief summary
The aim of the trial is to assess the relative bioavailability of fixed dose combination tablets of Empagliflozin and metformin compared to the administration of single tablets (Empagliflozin and metformin ) in Chinese subjects. The availability of a fixed dose combination tablet is expected to significantly enhance patient's compliance with antidiabetic treatment, in particular with concern to the frequent polypharmacy in diabetic patients.
Interventions
DRUG5 mg empagliflozin/850 mg metformin FDC
5 mg empagliflozin/850 mg metformin FDC
DRUG12.5 mg empagliflozin
10 mg empagliflozin tablet and 2.5 mg empagliflozin tablet
DRUG850 mg metformin
850mg metformin tablet
DRUG5 mg empagliflozin
5 mg empagliflozin
DRUG12.5 mg empagliflozin/850 mg metformin FDC
12.5 mg empagliflozin/850 mg metformin FDC
DRUG12.5 mg empagliflozin/500 mg metformin FDC
12.5 mg empagliflozin/500 mg metformin FDC
DRUG5 mg empagliflozin/500 mg metformin FDC
5 mg empagliflozin/500 mg metformin FDC
DRUG500 mg metformin
500 mg metformin
Sponsors
Eli Lilly and Company
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 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 |
|---|---|---|
| AUC(0-∞) for Empagliflozin | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity |
| AUC(0-∞) for Metformin | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity |
| Cmax for Empagliflozin | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Maximum measured concentration of the empagliflozin in plasma |
| Cmax for Metformin | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Maximum measured concentration of the metformin in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-tz) of Empagliflozin | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 up to the last quantifiable data point |
| AUC(0-tz) of Metformin | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | Area under the concentration-time curve of the metformin in plasma over the time interval from 0 up to the last quantifiable data point |
Countries
China
Participant flow
Recruitment details
The study was performed as an open-label, randomised, single-dose, two-way crossover trial consisting of four trial parts. In each trial part the aim was to investigate the relative bioavailability of the Test treatment (T) and to compare it with the Reference treatment (R).
Participants by arm
| Arm | Count |
|---|---|
| T1R1 Study Part 1:
T1: Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin R1: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg; A washout period of at least 7 days was to be maintained between T1 and R1. | 12 |
| R1T1 Study Part 1:
R1: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg T1: Oral administration of a single FDC tablet 12.5 mg empagliflozin/850 mg metformin; A washout period of at least 7 days was to be maintained between R1 and T1. | 12 |
| T2R2 Study Part 2:
T2: Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin R2: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg; A washout period of at least 7 days was to be maintained between T2 and R2. | 12 |
| R2T2 Study part 2:
R2: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg; T2: Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin; A washout period of at least 7 days was to be maintained between R2 and T2. | 12 |
| T3R3 Study Part 3:
T3: Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin R3: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg; A washout period of at least 7 days was to be maintained between T3 and R3. | 12 |
| R3T3 Study Part 3:
R3: Oral administration of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg T3: Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin; A washout period of at least 7 days was to be maintained between R3 and T3 | 12 |
| T4R4 Study Part 4:
T4: Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin R4: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg; A washout period of at least 7 days was to be maintained between T4 and R4. | 12 |
| R4T4 Study Part 4:
R4: Oral administration of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg; T4: Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin; A washout period of at least 7 days was to be maintained between R4 and T4 | 12 |
| Total | 96 |
Baseline characteristics
| Characteristic | T1R1 | R1T1 | T2R2 | R2T2 | T3R3 | R3T3 | T4R4 | R4T4 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 26.9 years STANDARD_DEVIATION 4.8 | 27.0 years STANDARD_DEVIATION 5.3 | 26.8 years STANDARD_DEVIATION 5.3 | 24.3 years STANDARD_DEVIATION 3.4 | 24.8 years STANDARD_DEVIATION 4.3 | 24.4 years STANDARD_DEVIATION 3.9 | 24.6 years STANDARD_DEVIATION 3.7 | 25.6 years STANDARD_DEVIATION 4.8 | 25.5 years STANDARD_DEVIATION 4.5 |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 7 Participants | 5 Participants | 5 Participants | 7 Participants | 5 Participants | 7 Participants | 48 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 5 Participants | 7 Participants | 7 Participants | 5 Participants | 7 Participants | 5 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 24 | 8 / 24 | 9 / 24 | 11 / 24 | 12 / 24 | 11 / 24 | 7 / 24 | 9 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
AUC(0-∞) for Empagliflozin
Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity
Time frame: 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic set (PKS):~The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1 (FDC) | AUC(0-∞) for Empagliflozin | 4330 nmol * h/L | Geometric Coefficient of Variation 16.6 |
| R1 (FC) | AUC(0-∞) for Empagliflozin | 4110 nmol * h/L | Geometric Coefficient of Variation 15.3 |
| T2 (FDC) | AUC(0-∞) for Empagliflozin | 1680 nmol * h/L | Geometric Coefficient of Variation 22 |
| R2 (FC) | AUC(0-∞) for Empagliflozin | 1630 nmol * h/L | Geometric Coefficient of Variation 21.1 |
| T3 (FDC) | AUC(0-∞) for Empagliflozin | 4200 nmol * h/L | Geometric Coefficient of Variation 20.3 |
| R3 (FC) | AUC(0-∞) for Empagliflozin | 4060 nmol * h/L | Geometric Coefficient of Variation 18.6 |
| T4 (FDC) | AUC(0-∞) for Empagliflozin | 1610 nmol * h/L | Geometric Coefficient of Variation 16.5 |
| R4 (FC) | AUC(0-∞) for Empagliflozin | 1560 nmol * h/L | Geometric Coefficient of Variation 17.7 |
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [101.92, 108.78]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.91, 106.65]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.73, 107.54]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.36, 106.37]ANOVA
Primary
AUC(0-∞) for Metformin
Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity
Time frame: 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic set (PKS):~The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1 (FDC) | AUC(0-∞) for Metformin | 11600 ng * h/mL | Geometric Coefficient of Variation 18.9 |
| R1 (FC) | AUC(0-∞) for Metformin | 11100 ng * h/mL | Geometric Coefficient of Variation 17.4 |
| T2 (FDC) | AUC(0-∞) for Metformin | 11700 ng * h/mL | Geometric Coefficient of Variation 21.8 |
| R2 (FC) | AUC(0-∞) for Metformin | 11000 ng * h/mL | Geometric Coefficient of Variation 24 |
| T3 (FDC) | AUC(0-∞) for Metformin | 7800 ng * h/mL | Geometric Coefficient of Variation 18.9 |
| R3 (FC) | AUC(0-∞) for Metformin | 7510 ng * h/mL | Geometric Coefficient of Variation 17.8 |
| T4 (FDC) | AUC(0-∞) for Metformin | 7030 ng * h/mL | Geometric Coefficient of Variation 20.7 |
| R4 (FC) | AUC(0-∞) for Metformin | 7340 ng * h/mL | Geometric Coefficient of Variation 18.8 |
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000190% CI: [97.56, 112.07]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000190% CI: [99.32, 112.7]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [98.18, 109.63]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [89.88, 102.03]ANOVA
Primary
Cmax for Empagliflozin
Maximum measured concentration of the empagliflozin in plasma
Time frame: 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic set (PKS):~The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1 (FDC) | Cmax for Empagliflozin | 644 nmol/L | Geometric Coefficient of Variation 18.2 |
| R1 (FC) | Cmax for Empagliflozin | 605 nmol/L | Geometric Coefficient of Variation 15.3 |
| T2 (FDC) | Cmax for Empagliflozin | 263 nmol/L | Geometric Coefficient of Variation 17.7 |
| R2 (FC) | Cmax for Empagliflozin | 237 nmol/L | Geometric Coefficient of Variation 20.7 |
| T3 (FDC) | Cmax for Empagliflozin | 569 nmol/L | Geometric Coefficient of Variation 22.1 |
| R3 (FC) | Cmax for Empagliflozin | 561 nmol/L | Geometric Coefficient of Variation 25.3 |
| T4 (FDC) | Cmax for Empagliflozin | 228 nmol/L | Geometric Coefficient of Variation 16.4 |
| R4 (FC) | Cmax for Empagliflozin | 221 nmol/L | Geometric Coefficient of Variation 22.2 |
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [100.44, 112.8]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.002190% CI: [103.8, 118.24]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [94.82, 108.39]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000290% CI: [95.08, 111.63]ANOVA
Primary
Cmax for Metformin
Maximum measured concentration of the metformin in plasma
Time frame: 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic set (PKS):~The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1 (FDC) | Cmax for Metformin | 1920 ng/mL | Geometric Coefficient of Variation 20.9 |
| R1 (FC) | Cmax for Metformin | 1830 ng/mL | Geometric Coefficient of Variation 16.6 |
| T2 (FDC) | Cmax for Metformin | 1950 ng/mL | Geometric Coefficient of Variation 26.4 |
| R2 (FC) | Cmax for Metformin | 1840 ng/mL | Geometric Coefficient of Variation 26 |
| T3 (FDC) | Cmax for Metformin | 1290 ng/mL | Geometric Coefficient of Variation 22.2 |
| R3 (FC) | Cmax for Metformin | 1230 ng/mL | Geometric Coefficient of Variation 27.1 |
| T4 (FDC) | Cmax for Metformin | 1150 ng/mL | Geometric Coefficient of Variation 25.5 |
| R4 (FC) | Cmax for Metformin | 1190 ng/mL | Geometric Coefficient of Variation 21.3 |
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.29, 110.86]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000890% CI: [98.39, 114.88]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000390% CI: [96.68, 112.82]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000490% CI: [88.9, 104.99]ANOVA
Secondary
AUC(0-tz) of Empagliflozin
Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 up to the last quantifiable data point
Time frame: 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic set (PKS):~The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1 (FDC) | AUC(0-tz) of Empagliflozin | 4270 nmol * h/L | Geometric Coefficient of Variation 16.6 |
| R1 (FC) | AUC(0-tz) of Empagliflozin | 4060 nmol * h/L | Geometric Coefficient of Variation 14.7 |
| T2 (FDC) | AUC(0-tz) of Empagliflozin | 1650 nmol * h/L | Geometric Coefficient of Variation 21.5 |
| R2 (FC) | AUC(0-tz) of Empagliflozin | 1600 nmol * h/L | Geometric Coefficient of Variation 21 |
| T3 (FDC) | AUC(0-tz) of Empagliflozin | 4140 nmol * h/L | Geometric Coefficient of Variation 19.7 |
| R3 (FC) | AUC(0-tz) of Empagliflozin | 4010 nmol * h/L | Geometric Coefficient of Variation 18.5 |
| T4 (FDC) | AUC(0-tz) of Empagliflozin | 1580 nmol * h/L | Geometric Coefficient of Variation 16.7 |
| R4 (FC) | AUC(0-tz) of Empagliflozin | 1540 nmol * h/L | Geometric Coefficient of Variation 17.7 |
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [101.97, 108.45]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.75, 106.5]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.37, 107.04]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.1, 106.25]ANOVA
Secondary
AUC(0-tz) of Metformin
Area under the concentration-time curve of the metformin in plasma over the time interval from 0 up to the last quantifiable data point
Time frame: 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Population: Pharmacokinetic set (PKS):~The PKS included all evaluable subjects of the TS who provided at least 1 observation for at least 1 primary PK endpoint in both treatment periods without Important protocol violations (IPV) relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1 (FDC) | AUC(0-tz) of Metformin | 11400 ng* h/mL | Geometric Coefficient of Variation 19.2 |
| R1 (FC) | AUC(0-tz) of Metformin | 10800 ng* h/mL | Geometric Coefficient of Variation 17.6 |
| T2 (FDC) | AUC(0-tz) of Metformin | 11400 ng* h/mL | Geometric Coefficient of Variation 23.1 |
| R2 (FC) | AUC(0-tz) of Metformin | 10800 ng* h/mL | Geometric Coefficient of Variation 25.1 |
| T3 (FDC) | AUC(0-tz) of Metformin | 7630 ng* h/mL | Geometric Coefficient of Variation 18.9 |
| R3 (FC) | AUC(0-tz) of Metformin | 7420 ng* h/mL | Geometric Coefficient of Variation 17.9 |
| T4 (FDC) | AUC(0-tz) of Metformin | 6790 ng* h/mL | Geometric Coefficient of Variation 24.7 |
| R4 (FC) | AUC(0-tz) of Metformin | 7230 ng* h/mL | Geometric Coefficient of Variation 18.3 |
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [99.34, 111.68]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000190% CI: [99.09, 112.85]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 090% CI: [97.11, 109.03]ANOVA
Comparison: The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. This model included effects accounting for the following sources of variation:~'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.p-value: 0.000290% CI: [87.74, 100.36]ANOVA