Trial Outcomes & Findings for Bioavailability of Empagliflozin/Metformin Fixed Dose Combinations (FDCs) in Healthy Chinese Volunteers (NCT NCT02102932)

Results Overview

Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

96 participants

Primary outcome timeframe

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

Results posted on

2015-09-24

Participant Flow

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).

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.	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.	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	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.	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
Overall Study STARTED	12	12	12	12	12	12	12	12
Overall Study COMPLETED	12	12	12	12	12	12	12	12
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bioavailability of Empagliflozin/Metformin Fixed Dose Combinations (FDCs) in Healthy Chinese Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	T1R1 n=12 Participants 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.	R1T1 n=12 Participants 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.	T2R2 n=12 Participants 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.	R2T2 n=12 Participants 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.	T3R3 n=12 Participants 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.	R3T3 n=12 Participants 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	T4R4 n=12 Participants 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.	R4T4 n=12 Participants 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	Total n=96 Participants Total of all reporting groups
Age, Continuous	26.9 years STANDARD_DEVIATION 4.8 • n=5 Participants	27.0 years STANDARD_DEVIATION 5.3 • n=7 Participants	26.8 years STANDARD_DEVIATION 5.3 • n=5 Participants	24.3 years STANDARD_DEVIATION 3.4 • n=4 Participants	24.8 years STANDARD_DEVIATION 4.3 • n=21 Participants	24.4 years STANDARD_DEVIATION 3.9 • n=10 Participants	24.6 years STANDARD_DEVIATION 3.7 • n=115 Participants	25.6 years STANDARD_DEVIATION 4.8 • n=6 Participants	25.5 years STANDARD_DEVIATION 4.5 • n=6 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	7 Participants n=10 Participants	5 Participants n=115 Participants	7 Participants n=6 Participants	48 Participants n=6 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	7 Participants n=21 Participants	5 Participants n=10 Participants	7 Participants n=115 Participants	5 Participants n=6 Participants	48 Participants n=6 Participants

PRIMARY outcome

Timeframe: 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.

Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity

Outcome measures

Outcome measures
Measure	T1 (FDC) n=24 Participants Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin	R1 (FC) n=24 Participants Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg	T2 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin	R2 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg	T3 (FDC) n=24 Participants Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin	R3 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg	T4 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin	R4 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
AUC(0-∞) for Empagliflozin	4330 nmol * h/L Geometric Coefficient of Variation 16.6	4110 nmol * h/L Geometric Coefficient of Variation 15.3	1680 nmol * h/L Geometric Coefficient of Variation 22.0	1630 nmol * h/L Geometric Coefficient of Variation 21.1	4200 nmol * h/L Geometric Coefficient of Variation 20.3	4060 nmol * h/L Geometric Coefficient of Variation 18.6	1610 nmol * h/L Geometric Coefficient of Variation 16.5	1560 nmol * h/L Geometric Coefficient of Variation 17.7

PRIMARY outcome

Timeframe: 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.

Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity

Outcome measures

Outcome measures
Measure	T1 (FDC) n=24 Participants Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin	R1 (FC) n=24 Participants Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg	T2 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin	R2 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg	T3 (FDC) n=24 Participants Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin	R3 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg	T4 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin	R4 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
AUC(0-∞) for Metformin	11600 ng * h/mL Geometric Coefficient of Variation 18.9	11100 ng * h/mL Geometric Coefficient of Variation 17.4	11700 ng * h/mL Geometric Coefficient of Variation 21.8	11000 ng * h/mL Geometric Coefficient of Variation 24.0	7800 ng * h/mL Geometric Coefficient of Variation 18.9	7510 ng * h/mL Geometric Coefficient of Variation 17.8	7030 ng * h/mL Geometric Coefficient of Variation 20.7	7340 ng * h/mL Geometric Coefficient of Variation 18.8

PRIMARY outcome

Timeframe: 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.

Maximum measured concentration of the empagliflozin in plasma

Outcome measures

Outcome measures
Measure	T1 (FDC) n=24 Participants Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin	R1 (FC) n=24 Participants Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg	T2 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin	R2 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg	T3 (FDC) n=24 Participants Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin	R3 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg	T4 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin	R4 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Cmax for Empagliflozin	644 nmol/L Geometric Coefficient of Variation 18.2	605 nmol/L Geometric Coefficient of Variation 15.3	263 nmol/L Geometric Coefficient of Variation 17.7	237 nmol/L Geometric Coefficient of Variation 20.7	569 nmol/L Geometric Coefficient of Variation 22.1	561 nmol/L Geometric Coefficient of Variation 25.3	228 nmol/L Geometric Coefficient of Variation 16.4	221 nmol/L Geometric Coefficient of Variation 22.2

PRIMARY outcome

Timeframe: 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.

Maximum measured concentration of the metformin in plasma

Outcome measures

Outcome measures
Measure	T1 (FDC) n=24 Participants Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin	R1 (FC) n=24 Participants Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg	T2 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin	R2 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg	T3 (FDC) n=24 Participants Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin	R3 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg	T4 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin	R4 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
Cmax for Metformin	1920 ng/mL Geometric Coefficient of Variation 20.9	1830 ng/mL Geometric Coefficient of Variation 16.6	1950 ng/mL Geometric Coefficient of Variation 26.4	1840 ng/mL Geometric Coefficient of Variation 26.0	1290 ng/mL Geometric Coefficient of Variation 22.2	1230 ng/mL Geometric Coefficient of Variation 27.1	1150 ng/mL Geometric Coefficient of Variation 25.5	1190 ng/mL Geometric Coefficient of Variation 21.3

SECONDARY outcome

Timeframe: 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.

Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 up to the last quantifiable data point

Outcome measures

Outcome measures
Measure	T1 (FDC) n=24 Participants Oral administration of a single fixed dose combination (FDC) tablet 12.5 mg empagliflozin/850 mg metformin	R1 (FC) n=24 Participants Oral administration of free combination (FC) of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 850 mg	T2 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/850 mg metformin	R2 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 850 mg	T3 (FDC) n=24 Participants Oral administration of a single FDC tablet 12.5 mg empagliflozin/500 mg metformin	R3 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 10 mg + 1 tablet empagliflozin 2.5 mg + 1 tablet Glucophage® 500 mg	T4 (FDC) n=24 Participants Oral administration of a single FDC tablet 5 mg empagliflozin/500 mg metformin	R4 (FC) n=24 Participants Oral administration of FC of 1 tablet empagliflozin 5 mg + 1 tablet Glucophage® 500 mg
AUC(0-tz) of Empagliflozin	4270 nmol * h/L Geometric Coefficient of Variation 16.6	4060 nmol * h/L Geometric Coefficient of Variation 14.7	1650 nmol * h/L Geometric Coefficient of Variation 21.5	1600 nmol * h/L Geometric Coefficient of Variation 21.0	4140 nmol * h/L Geometric Coefficient of Variation 19.7	4010 nmol * h/L Geometric Coefficient of Variation 18.5	1580 nmol * h/L Geometric Coefficient of Variation 16.7	1540 nmol * h/L Geometric Coefficient of Variation 17.7

SECONDARY outcome

Timeframe: 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.

Area under the concentration-time curve of the metformin in plasma over the time interval from 0 up to the last quantifiable data point