Trial Outcomes & Findings for 4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM) (NCT NCT00885118)

NCT ID: NCT00885118

Last Updated: 2014-11-25

Results Overview

Change from baseline in Urine glucose excretion to 28 days

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: baseline and 28 days
• Results posted on: 2014-11-25

Participant Flow

Participant milestones

Measure	Placebo Treatment with placebo once daily	Empa 1 mg Treatment with Empa 1 mg once daily	Empa 5 mg Treatment with Empa 5 mg once daily	Empa 10 mg Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Overall Study STARTED	21	19	21	20	19
Overall Study COMPLETED	20	19	20	20	18
Overall Study NOT COMPLETED	1	0	1	0	1

Reasons for withdrawal

Measure	Placebo Treatment with placebo once daily	Empa 1 mg Treatment with Empa 1 mg once daily	Empa 5 mg Treatment with Empa 5 mg once daily	Empa 10 mg Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Overall Study Adverse Event	1	0	0	0	0
Overall Study Withdrawal by Subject	0	0	0	0	1
Overall Study Other reason not defined above	0	0	1	0	0

Baseline Characteristics

4 Weeks Treatment With Empagliflozin (BI 10773) in Japanese Type 2 Diabetic Patients (T2DM)

Baseline characteristics by cohort

Measure	Placebo n=21 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=21 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=20 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=19 Participants Treatment with Empa 25 mg once daily	Total n=100 Participants Total of all reporting groups
Age, Continuous	57.2 years STANDARD_DEVIATION 10.0 • n=5 Participants	58.6 years STANDARD_DEVIATION 8.2 • n=7 Participants	53.9 years STANDARD_DEVIATION 9.9 • n=5 Participants	55.8 years STANDARD_DEVIATION 8.0 • n=4 Participants	60.8 years STANDARD_DEVIATION 8.7 • n=21 Participants	57.2 years STANDARD_DEVIATION 9.2 • n=10 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	16 Participants n=10 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants	17 Participants n=4 Participants	15 Participants n=21 Participants	84 Participants n=10 Participants

PRIMARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in Urine glucose excretion to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in Urine Glucose Excretion	599.763 mg Standard Error 4497.460	43428.245 mg Standard Error 4598.593	81564.440 mg Standard Error 4460.086	89189.527 mg Standard Error 4704.967	86220.111 mg Standard Error 4828.541

PRIMARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in Fasting plasma glucose to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in Fasting Plasma Glucose	-15.436 mg/dL Standard Error 2.860	-28.116 mg/dL Standard Error 2.965	-35.355 mg/dL Standard Error 2.865	-41.643 mg/dL Standard Error 3.009	-42.670 mg/dL Standard Error 3.089

PRIMARY outcome

Timeframe: baseline and 27 days

Population: Full analysis set (FAS)

Change from baseline in 8-point glucose to 27 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in 8-point Glucose	-17.381 mg/dL Standard Error 3.932	-35.263 mg/dL Standard Error 4.121	-39.867 mg/dL Standard Error 3.903	-43.646 mg/dL Standard Error 4.113	-45.721 mg/dL Standard Error 4.187

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in HbA1c to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in HbA1c	-0.420 percentage of HbA1c Standard Error 0.089	-0.659 percentage of HbA1c Standard Error 0.093	-0.717 percentage of HbA1c Standard Error 0.090	-0.849 percentage of HbA1c Standard Error 0.094	-0.815 percentage of HbA1c Standard Error 0.096

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in Fructosamine to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in Fructosamine	-8.436 umol/L Standard Error 12.289	4.091 umol/L Standard Error 12.663	-2.453 umol/L Standard Error 12.362	-26.294 umol/L Standard Error 12.933	-28.275 umol/L Standard Error 13.282

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in 1,5-anhydroglucitol to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=12 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=11 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=10 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=4 Participants Treatment with Empa 25 mg once daily
Change From Baseline in 1,5-anhydroglucitol	1.174 ug/mL Standard Error 0.439	-3.018 ug/mL Standard Error 0.581	-3.435 ug/mL Standard Error 0.615	-2.863 ug/mL Standard Error 0.622	-3.713 ug/mL Standard Error 0.982

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in Fasting insulin to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in Fasting Insulin	-0.387 uU/mL Standard Error 0.287	-0.866 uU/mL Standard Error 0.295	-0.766 uU/mL Standard Error 0.287	-1.730 uU/mL Standard Error 0.301	-1.643 uU/mL Standard Error 0.312

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in the area under the curve of plasma glucose levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in the Area Under the Curve of Plasma Glucose Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)	-81.357 hr*mg/dL Standard Error 10.481	-176.771 hr*mg/dL Standard Error 10.924	-190.837 hr*mg/dL Standard Error 10.554	-212.693 hr*mg/dL Standard Error 11.023	-217.698 hr*mg/dL Standard Error 11.247

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in the area under the curve of glucagon levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in the Area Under the Curve of Glucagon Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)	-23.452 hr*pg/mL Standard Error 9.177	-0.785 hr*pg/mL Standard Error 9.383	7.124 hr*pg/mL Standard Error 9.138	-17.478 hr*pg/mL Standard Error 9.635	-12.437 hr*pg/mL Standard Error 9.964

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Full analysis set (FAS)

Change from baseline in the area under the curve of insulin levels until 4 hours after intake of a standardised food (meal tolerance test) to 28 days

Outcome measures

Measure	Placebo n=20 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=18 Participants Treatment with Empa 10 mg once daily	Empa 25 mg n=17 Participants Treatment with Empa 25 mg once daily
Change From Baseline in the Area Under the Curve of Insulin Levels Until 4 Hours After Intake of a Standardised Food (Meal Tolerance Test)	2.948 hr*uU/mL Standard Error 2.819	-5.921 hr*uU/mL Standard Error 2.896	-11.396 hr*uU/mL Standard Error 2.811	-12.695 hr*uU/mL Standard Error 2.982	-7.170 hr*uU/mL Standard Error 3.048

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

Area under the concentration-time curve of the analyte in plasma after administration of the first dose over a uniform dosing interval τ

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
AUCτ,1	216 nmol*h/L Geometric Coefficient of Variation 18.4	938 nmol*h/L Geometric Coefficient of Variation 44.2	2040 nmol*h/L Geometric Coefficient of Variation 19.4	5190 nmol*h/L Geometric Coefficient of Variation 18.6	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

area under the concentration-time curve of the analyte in plasma over the time interval from 0 to last quantifiable plasma concentration

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
AUC0-tz	216 nmol*h/L Geometric Coefficient of Variation 18.4	937 nmol*h/L Geometric Coefficient of Variation 44.2	2040 nmol*h/L Geometric Coefficient of Variation 19.5	5180 nmol*h/L Geometric Coefficient of Variation 18.6	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

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

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
AUC0-∞	249 nmol*h/L Geometric Coefficient of Variation 15.5	1070 nmol*h/L Geometric Coefficient of Variation 44.5	2320 nmol*h/L Geometric Coefficient of Variation 18.1	5930 nmol*h/L Geometric Coefficient of Variation 18.6	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

maximum measured concentration of the analyte in plasma

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Cmax	38.5 nmol/L Geometric Coefficient of Variation 28.8	166 nmol/L Geometric Coefficient of Variation 47.6	358 nmol/L Geometric Coefficient of Variation 29.1	844 nmol/L Geometric Coefficient of Variation 15.7	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

terminal half-life of the analyte in plasma

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=21 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
t1/2	9.55 hour Geometric Coefficient of Variation 14.8	9.09 hour Geometric Coefficient of Variation 15.0	9.14 hour Geometric Coefficient of Variation 13.3	9.26 hour Geometric Coefficient of Variation 15.8	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

apparent clearance of the analyte in plasma after extravascular administration

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
CL/F	149 mL/min Geometric Coefficient of Variation 15.5	173 mL/min Geometric Coefficient of Variation 44.5	159 mL/min Geometric Coefficient of Variation 18.1	156 mL/min Geometric Coefficient of Variation 18.6	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

apparent volume of distribution during the terminal phase λz following an extravascular dose

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Vz/F	123 Liter Geometric Coefficient of Variation 26.1	136 Liter Geometric Coefficient of Variation 46.3	126 Liter Geometric Coefficient of Variation 25.5	125 Liter Geometric Coefficient of Variation 25.3	—

SECONDARY outcome

Timeframe: 0-5, 5-12, 12-24 hour after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

amount of the analyte that is eliminated in urine over the time interval 0 to 24

Outcome measures

Measure	Placebo n=18 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Ae0-24	338 nmol Geometric Coefficient of Variation 23.7	1640 nmol Geometric Coefficient of Variation 56.2	3460 nmol Geometric Coefficient of Variation 17.5	8550 nmol Geometric Coefficient of Variation 17.0	—

SECONDARY outcome

Timeframe: 0-5, 5-12, 12-24 hour after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

fraction of the analyte excreted unchanged in urine from time interval 0 to 24

Outcome measures

Measure	Placebo n=18 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
fe0-24	15.2 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 23.7	14.8 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 56.2	15.6 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 17.5	15.4 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 17.0	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min, 0-5h, 5-12h, 12-24h after first drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

renal clearance of the analyte in plasma after extravascular administration - based on 0-24 hours data

Outcome measures

Measure	Placebo n=18 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=20 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=19 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
CLR,0-24	25.7 mL/min Geometric Coefficient of Variation 21.2	28.7 mL/min Geometric Coefficient of Variation 27.3	28.3 mL/min Geometric Coefficient of Variation 24.4	27.5 mL/min Geometric Coefficient of Variation 23.4	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ at steady state

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
AUCτ,ss	277 nmol*h/L Geometric Coefficient of Variation 17.0	1270 nmol*h/L Geometric Coefficient of Variation 15.0	2580 nmol*h/L Geometric Coefficient of Variation 17.3	6330 nmol*h/L Geometric Coefficient of Variation 20.3	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

maximum measured concentration of the analyte in plasma at steady state

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Cmax,ss	41.4 nmol/L Geometric Coefficient of Variation 32.3	182 nmol/L Geometric Coefficient of Variation 31.4	393 nmol/L Geometric Coefficient of Variation 28.0	836 nmol/L Geometric Coefficient of Variation 29.2	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

terminal half-life of the analyte in plasma at steady state

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
t1/2,ss	12.2 hour Geometric Coefficient of Variation 45.5	11.9 hour Geometric Coefficient of Variation 48.0	13.4 hour Geometric Coefficient of Variation 37.7	16.4 hour Geometric Coefficient of Variation 48.4	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

apparent clearance of the analyte in plasma after extravascular administration at steady state

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
CL/F,ss	133 mL/min Geometric Coefficient of Variation 17.0	146 mL/min Geometric Coefficient of Variation 15.0	143 mL/min Geometric Coefficient of Variation 17.3	146 mL/min Geometric Coefficient of Variation 20.3	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h 48h, 72h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Vz/F,ss	141 Liter Geometric Coefficient of Variation 37.8	151 Liter Geometric Coefficient of Variation 48.6	166 Liter Geometric Coefficient of Variation 43.6	208 Liter Geometric Coefficient of Variation 51.6	—

SECONDARY outcome

Timeframe: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on Cmax

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
RA,Cmax	1.08 ratio Geometric Coefficient of Variation 23.3	1.07 ratio Geometric Coefficient of Variation 54.2	1.16 ratio Geometric Coefficient of Variation 34.2	0.998 ratio Geometric Coefficient of Variation 30.4	—

SECONDARY outcome

Timeframe: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 23h55min after first drug administration, and predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

accumulation ratios of the analyte in plasma after 28 doses (once daily) over a uniform dosing interval τ, based on AUCτ

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=19 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
RA,AUC	1.28 ratio Geometric Coefficient of Variation 9.21	1.32 ratio Geometric Coefficient of Variation 42.5	1.32 ratio Geometric Coefficient of Variation 13.1	1.23 ratio Geometric Coefficient of Variation 12.7	—

SECONDARY outcome

Timeframe: 0-5, 5-12, 12-24 hour after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

amount of the analyte that is eliminated in urine at steady state over the time interval 0 to 24

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
Ae0-24,ss	479 nmol Geometric Coefficient of Variation 27.2	2250 nmol Geometric Coefficient of Variation 44.5	4780 nmol Geometric Coefficient of Variation 18.6	11500 nmol Geometric Coefficient of Variation 24.3	—

SECONDARY outcome

Timeframe: 0-5, 5-12, 12-24 hour after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

fraction of the analyte excreted unchanged in urine at steady state from time interval 0 to 24

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
fe0-24,ss	21.6 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 27.2	20.3 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 44.5	21.6 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 18.6	20.8 percentage of Ae0-24 (to dosage) Geometric Coefficient of Variation 24.3	—

SECONDARY outcome

Timeframe: Predose and 15 minutes (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 0-5h, 5-12h, 12-24h after last drug administration

Population: Pharmacokinetic analysis set: all patients who received at least one dose of BI 10773 and had some pharmacokinetic data

renal clearance of the analyte at steady state determined over the dosing interval τ

Outcome measures

Measure	Placebo n=19 Participants Treatment with placebo once daily	Empa 1 mg n=20 Participants Treatment with Empa 1 mg once daily	Empa 5 mg n=18 Participants Treatment with Empa 5 mg once daily	Empa 10 mg n=17 Participants Treatment with Empa 10 mg once daily	Empa 25 mg Treatment with Empa 25 mg once daily
CLR,ss	28.8 mL/min Geometric Coefficient of Variation 25.2	29.6 mL/min Geometric Coefficient of Variation 40.5	30.9 mL/min Geometric Coefficient of Variation 28.1	30.3 mL/min Geometric Coefficient of Variation 28.3	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Empa 1 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Empa 5 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Empa 10 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Empa 25 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=21 participants at risk Treatment with placebo once daily	Empa 1 mg n=19 participants at risk Treatment with Empa 1 mg once daily	Empa 5 mg n=21 participants at risk Treatment with Empa 5 mg once daily	Empa 10 mg n=20 participants at risk Treatment with Empa 10 mg once daily	Empa 25 mg n=19 participants at risk Treatment with Empa 25 mg once daily
Nervous system disorders Transient ischaemic attack	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.

Other adverse events

Measure	Placebo n=21 participants at risk Treatment with placebo once daily	Empa 1 mg n=19 participants at risk Treatment with Empa 1 mg once daily	Empa 5 mg n=21 participants at risk Treatment with Empa 5 mg once daily	Empa 10 mg n=20 participants at risk Treatment with Empa 10 mg once daily	Empa 25 mg n=19 participants at risk Treatment with Empa 25 mg once daily
Infections and infestations Nasopharyngitis	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	10.5% 2/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	4.8% 1/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Infections and infestations Cystitis	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Metabolism and nutrition disorders Hyperglycaemia	4.8% 1/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Eye disorders Dry eye	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	10.0% 2/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Gastrointestinal disorders Constipation	4.8% 1/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	4.8% 1/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	10.0% 2/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Gastrointestinal disorders Toothache	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.0% 1/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Renal and urinary disorders Pollakiuria	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
General disorders Oedema peripheral	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Investigations Alpha 1 microglobulin urine increased	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Investigations Beta 2 microglobulin urine increased	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Injury, poisoning and procedural complications Contusion	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Injury, poisoning and procedural complications Fall	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.
Injury, poisoning and procedural complications Heat illness	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	5.3% 1/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/21 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/20 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.	0.00% 0/19 • Between the first drug administration and the end of the trial after the last drug administration, up to 28 days.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@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