Trial Outcomes & Findings for Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Empagliflozin in Chinese Female and Male Patients With Type 2 Diabetes Mellitus (NCT NCT01316341)

NCT ID: NCT01316341

Last Updated: 2014-06-17

Results Overview

Maximum measured concentration of the analyte in plasma after the first dose on day 1.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 24 participants
• Primary outcome timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
• Results posted on: 2014-06-17

Participant Flow

Participant milestones

Measure	Placebo Two placebo tablets, one matching the empa 10mg tablet and one matching the empa 25mg tablet, taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period).	Empa 10 mg 10 mg Empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 25mg empa tablet was taken at each drug administration.	Empa 25 mg 25 mg Empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Overall Study STARTED	6	9	9
Overall Study COMPLETED	6	9	9
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Empagliflozin in Chinese Female and Male Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Placebo n=6 Participants Two placebo tablets, one matching the empa 10mg tablet and one matching the empa 25mg tablet, taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period).	Empa 10 mg n=9 Participants 10 mg Empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 25mg empa tablet was taken at each drug administration.	Empa 25 mg n=9 Participants 25 mg Empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.	Total n=24 Participants Total of all reporting groups
Age, Continuous	53.5 years STANDARD_DEVIATION 9.6 • n=5 Participants	54.1 years STANDARD_DEVIATION 7.9 • n=7 Participants	52.7 years STANDARD_DEVIATION 9.9 • n=5 Participants	53.4 years STANDARD_DEVIATION 8.7 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Maximum measured concentration of the analyte in plasma after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Maximum Measured Concentration (Cmax)	436 nmol/L Geometric Coefficient of Variation 14.1	1090 nmol/L Geometric Coefficient of Variation 29.2	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Time from dosing to the maximum measured concentration of the analyte in plasma, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Time to Maximum Measured Concentration (Tmax)	1.13 hours Geometric Coefficient of Variation 33.3	1.50 hours Geometric Coefficient of Variation 40.8	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity, after the first dose on day 1

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Area Under the Curve 0 to Infinity (AUC0-∞) After Single Dosing	2560 nmol*h/L Geometric Coefficient of Variation 12.3	7250 nmol*h/L Geometric Coefficient of Variation 24.4	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)	2510 nmol*h/L Geometric Coefficient of Variation 12.3	7070 nmol*h/L Geometric Coefficient of Variation 24.1	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Terminal Rate Constant in Plasma (λz), after the first dose on day 1

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Terminal Rate Constant (λz)	0.0749 1/h Geometric Coefficient of Variation 30.3	0.0664 1/h Geometric Coefficient of Variation 22.2	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Terminal half-life of empagliflozin (empa) in plasma after the first dose on day 1

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Terminal Half-life (t1/2)	9.25 hours Geometric Coefficient of Variation 30.3	10.4 hours Geometric Coefficient of Variation 22.2	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Mean residence time of empagliflozin (empa) in the body after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Mean Residence Time (MRTpo)	9.29 hours Geometric Coefficient of Variation 16.4	10.2 hours Geometric Coefficient of Variation 13.2	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Apparent clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Apparent Clearance of Empagliflozin After Extravascular Administration (CL/F)	144 mL/min Geometric Coefficient of Variation 12.3	127 mL/min Geometric Coefficient of Variation 24.4	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Apparent volume of distribution during the terminal phase λz, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Apparent Volume of Distribution During the Terminal Phase λz (Vz/F)	115 L Geometric Coefficient of Variation 31.8	115 L Geometric Coefficient of Variation 30.1	—

PRIMARY outcome

Timeframe: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Amount of empagliflozin (empa) eliminated in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Amount of Empagliflozin Eliminated in Urine in the Time Interval 0 Hours to 24 Hours (Ae 0-24)	4030 nmol Geometric Coefficient of Variation 18.9	9940 nmol Geometric Coefficient of Variation 23.8	—

PRIMARY outcome

Timeframe: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Fraction of empagliflozin (empa) excreted unchanged in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Fraction of Empagliflozin Excreted Unchanged in Urine in the Time Interval 0 Hours to 24 Hours (fe 0-24).	18.2 percentage of empa Geometric Coefficient of Variation 18.9	17.9 percentage of empa Geometric Coefficient of Variation 23.8	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Renal Clearance After Extravascular Administration (CL R,0-48)	28.9 mL/min Geometric Coefficient of Variation 22.6	25.6 mL/min Geometric Coefficient of Variation 31.8	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Maximum measured concentration of empagliflozin (empa) in plasma at steady state over a uniform dosing interval.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Maximum Measured Concentration Over a Uniform Dosing Interval (Cmax,ss)	489 nmol/L Geometric Coefficient of Variation 27.4	1250 nmol/L Geometric Coefficient of Variation 32.1	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Time from last dosing to maximum measured concentration of empagliflozin (empa) in plasma over a uniform dosing interval at steady state, after multiple dosing.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Time From Last Dosing to Maximum Measured Concentration Over a Uniform Dosing Interval at Steady State (Tmax,ss)	1.17 hours Geometric Coefficient of Variation 43.8	1.37 hours Geometric Coefficient of Variation 35.0	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Area under the concentration-time curve of empagliflozin (empa) in plasma at steady state over a uniform dosing interval, after multiple dosing

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Area Under the Concentration-time Curve in Plasma at Steady State Over a Uniform Dosing Interval (AUCτ,ss)	2650 nmol*h/L Geometric Coefficient of Variation 15.4	7520 nmol*h/L Geometric Coefficient of Variation 21.4	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Terminal rate constant in plasma at steady state, after multiple dosing.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Terminal Rate Constant in Plasma at Steady State (λz,ss)	0.0559 1/h Geometric Coefficient of Variation 52.5	0.0588 1/h Geometric Coefficient of Variation 24.6	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Terminal half-life of empagliflozin (empa) in plasma at steady state, after multiple dosing.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Terminal Half-life in Plasma at Steady State (t1/2,ss)	12.4 hours Geometric Coefficient of Variation 52.5	11.8 hours Geometric Coefficient of Variation 24.6	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Mean residence time of empagliflozin (empa) in the body at steady state after multiple oral administrations

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Mean Residence Time at Steady State (MRTpo,ss)	10.5 hours Geometric Coefficient of Variation 18.5	10.2 hours Geometric Coefficient of Variation 19.1	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Apparent clearance of empagliflozin (empa) in the plasma at steady state following multiple oral dose administration.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Apparent Clearance of Empagliflozin After Extravascular Administration (CL/Fss)	139 mL/min Geometric Coefficient of Variation 15.4	123 mL/min Geometric Coefficient of Variation 21.4	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Apparent volume of distribution during the terminal phase λz at steady state following oral administration after multiple dosing

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Apparent Volume of Distribution During the Terminal Phase λz (Vz/Fss)	150 L Geometric Coefficient of Variation 55.1	125 L Geometric Coefficient of Variation 29.9	—

PRIMARY outcome

Timeframe: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Amount of empagliflozin (empa) eliminated in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Amount of Analyte Eliminated in Urine at Steady State in Time Interval 0 Hours to 24 Hours (Ae 0-24,ss)	4420 nmol Geometric Coefficient of Variation 14.6	11600 nmol Geometric Coefficient of Variation 23.3	—

PRIMARY outcome

Timeframe: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Fraction of empagliflozin (empa) excreted unchanged in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Fraction of Empagliflozin Excreted Unchanged in Urine at Steady State in the Time Interval 0 Hours to 24 Hours (fe 0-24,ss)	19.9 percentage of empa Geometric Coefficient of Variation 14.6	20.9 percentage of empa Geometric Coefficient of Variation 23.3	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after multiple dosing.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Renal Clearance at Steady State (CL R,ss)	27.8 mL/min Geometric Coefficient of Variation 15.8	26.1 mL/min Geometric Coefficient of Variation 30.0	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration on days 1 and 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Accumulation ratio of empagliflozin (empa) based on AUC, after multiple dosing

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Accumulation Ratio Based on AUC (R A,AUC)	1.14 Ratio Geometric Coefficient of Variation 12.0	1.17 Ratio Geometric Coefficient of Variation 11.2	—

PRIMARY outcome

Timeframe: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration between days 5 and 9

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Accumulation ratio of empagliflozin (empa) based on Cmax, after multiple dosing

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Accumulation Ratio Based on Cmax (R A,Cmax)	1.12 Ratio Geometric Coefficient of Variation 32.0	1.15 Ratio Geometric Coefficient of Variation 30.8	—

PRIMARY outcome

Timeframe: 5 minutes before drug administration

Population: Pharmacokinetic (PK) analysis set included all evaluable patients documented to have taken at least one dose of investigational treatment and who provided at least one observation for at least one PK endpoint.

Predose plasma concentration of empagliflozin (empa) before planned dose by day.

This endpoint in steady state is identical to Cmin,ss.

Outcome measures

Measure	Empa 10 mg n=9 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Predose Plasma Concentration Before Planned Dose x (Cpre,x) Treatment Day 8	26.10 nmol/L Geometric Coefficient of Variation 1.22	72.74 nmol/L Geometric Coefficient of Variation 1.43	—
Predose Plasma Concentration Before Planned Dose x (Cpre,x) Treatment Day 5	24.64 nmol/L Geometric Coefficient of Variation 1.24	70.54 nmol/L Geometric Coefficient of Variation 1.48	—
Predose Plasma Concentration Before Planned Dose x (Cpre,x) Treatment Day 6	25.70 nmol/L Geometric Coefficient of Variation 1.23	80.27 nmol/L Geometric Coefficient of Variation 1.42	—
Predose Plasma Concentration Before Planned Dose x (Cpre,x) Treatment Day 7	25.24 nmol/L Geometric Coefficient of Variation 1.24	78.96 nmol/L Geometric Coefficient of Variation 1.57	—
Predose Plasma Concentration Before Planned Dose x (Cpre,x) Treatment Day 9	27.21 nmol/L Geometric Coefficient of Variation 1.23	76.02 nmol/L Geometric Coefficient of Variation 1.42	—

PRIMARY outcome

Timeframe: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Population: Pharmacodynamic analysis (PD) set included all patients documented to have taken at least one dose of investigational treatment, who received at least one dose of empagliflozin or placebo and who provided at least one baseline and post-treatment observation for at least one PD endpoint.

Change from day -1 in urinary glucose excretion in a 24 hour collection period per time point.

Outcome measures

Measure	Empa 10 mg n=6 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Urinary Glucose Excretion (UGE) Change From Baseline Day 1	-988.38 mg Standard Deviation 2791.68	87680.85 mg Standard Deviation 22924.91	82791.86 mg Standard Deviation 18752.81
Urinary Glucose Excretion (UGE) Change From Baseline Day 9	-4106.10 mg Standard Deviation 6428.12	95765.72 mg Standard Deviation 24133.47	82633.88 mg Standard Deviation 34757.02

PRIMARY outcome

Timeframe: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Population: Pharmacodynamic analysis (PD) set included all patients documented to have taken at least one dose of investigational treatment, who received at least one dose of empagliflozin or placebo and who provided at least one baseline and post-treatment observation for at least one PD endpoint.

Fasting Plasma Glucose (FPG) change from baseline between day 1 and day 9.

Outcome measures

Measure	Empa 10 mg n=6 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Fasting Plasma Glucose (FPG) Change From Baseline	-3.67 mg/dL Standard Deviation 7.45	-25.56 mg/dL Standard Deviation 20.74	-31.44 mg/dL Standard Deviation 26.92

SECONDARY outcome

Timeframe: Drug administration until end of trial, up to 21 days

Population: Treated set (TS) includes all patients who were documented to have taken at least one dose of investigational treatment.

Clinically relevant abnormalities for protocol-specified significant adverse events, hypoglycaemic events, vital signs, blood chemistry, use of rescue therapy, change in body weight and change in waist circumference.

Results shown are for hypoglycaemic events, as this was the only event that occurred for this endpoint.

Outcome measures

Measure	Empa 10 mg n=6 Participants 10 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 25mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally as a single dose, plus a placebo tablet matching the 10mg empa tablet.	Empa 25 mg n=9 Participants 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Clinical Relevant Abnormalities for Protocol-Specified Significant Adverse Events, Hypoglycaemic Events, Vital Signs, Blood Chemistry, Rescue Therapy, Body Weight and Waist Circumference	0 participants	1 participants	0 participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Empa 10 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Empa 25 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=6 participants at risk Two placebo tablets, one matching the empa 10mg tablet and one matching the empa 25mg tablet, taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period).	Empa 10 mg n=9 participants at risk 10 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 25mg empa tablet was taken at each drug administration.	Empa 25 mg n=9 participants at risk 25 mg empagliflozin (empa) taken orally either as a single dose (single dose period) or for 7 consecutive days (multiple dose period). Along with this a placebo tablet matching the 10mg empa tablet was taken at each drug administration.
Blood and lymphatic system disorders White blood cell disorder	0.00% 0/6 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days	11.1% 1/9 • Drug administration until end of trial, up to 21 days
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Drug administration until end of trial, up to 21 days	11.1% 1/9 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days
Gastrointestinal disorders Toothache	16.7% 1/6 • Drug administration until end of trial, up to 21 days	22.2% 2/9 • Drug administration until end of trial, up to 21 days	11.1% 1/9 • Drug administration until end of trial, up to 21 days
Investigations Eosinophil count abnormal	16.7% 1/6 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days
Investigations Neutrophil count abnormal	0.00% 0/6 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days	11.1% 1/9 • Drug administration until end of trial, up to 21 days
Renal and urinary disorders Pollakiuria	0.00% 0/6 • Drug administration until end of trial, up to 21 days	11.1% 1/9 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Drug administration until end of trial, up to 21 days	22.2% 2/9 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days
Skin and subcutaneous tissue disorders Purpura	0.00% 0/6 • Drug administration until end of trial, up to 21 days	11.1% 1/9 • Drug administration until end of trial, up to 21 days	0.00% 0/9 • Drug administration until end of trial, up to 21 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER