Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses of BI 10773 Tablets (NCT NCT01924767)
NCT ID: NCT01924767
Last Updated: 2014-07-04
Results Overview
Percentage of participants with clinically relevant findings in physical examination, vital signs and clinical laboratory tests. Relevant findings or worsenings of baseline conditions were reported as Adverse Events (cardiac disorders and investigations).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
day 1 to day 21
Results posted on
2014-07-04
Participant Flow
This Phase I trial was randomised, double-blind, and placebo-controlled within dose groups. It was to be performed in 48 female and male patients with type 2 diabetes in 4 sequential groups of 12 patients each. Within each dose group, 9 patients were to receive active drug and 3 were to receive placebo.
14 days wash-out of previous antidiabetic therapy followed by 8 days of once daily dosing at each dose level.
Participant milestones
| Measure |
Placebo
Patients were treated with matching placebo as tablet once daily (qd) in the morning.
|
Empagliflozin 2.5 mg qd
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
9
|
9
|
9
|
9
|
|
Overall Study
COMPLETED
|
11
|
9
|
8
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Patients were treated with matching placebo as tablet once daily (qd) in the morning.
|
Empagliflozin 2.5 mg qd
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses of BI 10773 Tablets
Baseline characteristics by cohort
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily in the morning.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
58.9 years
STANDARD_DEVIATION 6.4 • n=5 Participants
|
53.9 years
STANDARD_DEVIATION 10.9 • n=7 Participants
|
51.8 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 8.8 • n=4 Participants
|
60.3 years
STANDARD_DEVIATION 5.6 • n=21 Participants
|
56.9 years
STANDARD_DEVIATION 8.9 • n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
39 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: day 1 to day 21Population: Treated set.
Percentage of participants with clinically relevant findings in physical examination, vital signs and clinical laboratory tests. Relevant findings or worsenings of baseline conditions were reported as Adverse Events (cardiac disorders and investigations).
Outcome measures
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests
Cardiac disorders
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests
Investigations: Hepatic enzyme increased
|
8.3 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
PRIMARY outcome
Timeframe: day 1 to day 21Population: Treated set
Percentage of participants with clinically relevant findings in electrocardiogram (ECG) results
Outcome measures
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results
Clinically relevant
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results
Clinically irrelevant
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
PRIMARY outcome
Timeframe: Baseline and Day 9Population: Treated set
Micturition frequency is reported as change from pre-treatment to day 9 during the day, the night and total. Baseline is the mean of days 8-3 before drug administration.
Outcome measures
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Micturition Frequency
Micturition day frequency
|
4.1 frequency of micturition
Standard Deviation 1.8
|
2.6 frequency of micturition
Standard Deviation 2.1
|
5.0 frequency of micturition
Standard Deviation 1.6
|
3.9 frequency of micturition
Standard Deviation 1.5
|
4.4 frequency of micturition
Standard Deviation 2.1
|
|
Micturition Frequency
Micturition night frequency
|
0.3 frequency of micturition
Standard Deviation 1.6
|
0.2 frequency of micturition
Standard Deviation 1.2
|
0.5 frequency of micturition
Standard Deviation 0.5
|
0.6 frequency of micturition
Standard Deviation 1.6
|
0.7 frequency of micturition
Standard Deviation 0.9
|
|
Micturition Frequency
Micturition total frequency
|
4.5 frequency of micturition
Standard Deviation 2.1
|
2.8 frequency of micturition
Standard Deviation 2.6
|
5.5 frequency of micturition
Standard Deviation 1.5
|
4.4 frequency of micturition
Standard Deviation 2.4
|
5.1 frequency of micturition
Standard Deviation 2.2
|
PRIMARY outcome
Timeframe: day 21Population: Treated set
Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad.
Outcome measures
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Assessment of Tolerability by Investigator
Good
|
91.7 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
100.0 percentage of participants
|
|
Assessment of Tolerability by Investigator
Satisfactory
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Assessment of Tolerability by Investigator
Not satisfactory
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Assessment of Tolerability by Investigator
Bad
|
8.3 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1.-0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: Pharmacokinetic set (PK set) contains of all patients who received study medication and have evaluable pharmacokinetic parameter data. The PK set will not contain placebo patients.
Maximum concentration of the analyte in plasma (Cmax) after first dose, Maximum, minimum (Cmin) and average (Cavg) concentration of the analyte in plasma at steady-state, Concentration of analyte in plasma at 24 h after administration of the 8th dose (at steady-state) (C24,8)
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Concentration of the Analyte in Plasma
Cmax at steady-state (N=9,8,9,8)
|
66.6 nmol/L
Geometric Coefficient of Variation 26.7
|
272 nmol/L
Geometric Coefficient of Variation 30.1
|
622 nmol/L
Geometric Coefficient of Variation 17.4
|
2700 nmol/L
Geometric Coefficient of Variation 20.9
|
—
|
|
Concentration of the Analyte in Plasma
Cmin at steady-state (N=9,8,9,8)
|
4.41 nmol/L
Geometric Coefficient of Variation 36.9
|
23.5 nmol/L
Geometric Coefficient of Variation 31.5
|
47.1 nmol/L
Geometric Coefficient of Variation 35.3
|
243 nmol/L
Geometric Coefficient of Variation 32.0
|
—
|
|
Concentration of the Analyte in Plasma
Cavg at steady-state (N=9,8,9,8)
|
19.2 nmol/L
Geometric Coefficient of Variation 24.3
|
83.5 nmol/L
Geometric Coefficient of Variation 17.4
|
204 nmol/L
Geometric Coefficient of Variation 21.5
|
922 nmol/L
Geometric Coefficient of Variation 28.7
|
—
|
|
Concentration of the Analyte in Plasma
C24,8 (N=9,8,9,8)
|
4.55 nmol/L
Geometric Coefficient of Variation 36.8
|
23.8 nmol/L
Geometric Coefficient of Variation 31.7
|
47.2 nmol/L
Geometric Coefficient of Variation 35.2
|
249 nmol/L
Geometric Coefficient of Variation 27.6
|
—
|
|
Concentration of the Analyte in Plasma
Cmax after first dose
|
61.3 nmol/L
Geometric Coefficient of Variation 20.5
|
240 nmol/L
Geometric Coefficient of Variation 21.2
|
592 nmol/L
Geometric Coefficient of Variation 23.7
|
2670 nmol/L
Geometric Coefficient of Variation 26.1
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1.-0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
AUC0-∞: from 0 extrapolated to infinity after first dose AUCtau,1: over a uniform dosing interval tau after first dose AUCtau,ss: over a uniform dosing interval tau at steady-state AUCs were computed using the linear up/log down algorithm. If an analyte concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was to be used. If the analyte concentration was smaller than the preceding concentration, the logarithmic method was to be used.
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC)
AUC0-∞ after first dose
|
468 nmol*h/L
Geometric Coefficient of Variation 19.6
|
1890 nmol*h/L
Geometric Coefficient of Variation 14.7
|
4780 nmol*h/L
Geometric Coefficient of Variation 23.7
|
23300 nmol*h/L
Geometric Coefficient of Variation 19.4
|
—
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC)
AUC0-24 after first dose
|
397 nmol*h/L
Geometric Coefficient of Variation 17.6
|
1620 nmol*h/L
Geometric Coefficient of Variation 13.5
|
4200 nmol*h/L
Geometric Coefficient of Variation 23.6
|
19700 nmol*h/L
Geometric Coefficient of Variation 17.6
|
—
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC)
AUC0-tau at steady state (N=9,8,9,8)
|
460 nmol*h/L
Geometric Coefficient of Variation 24.3
|
2000 nmol*h/L
Geometric Coefficient of Variation 17.4
|
4890 nmol*h/L
Geometric Coefficient of Variation 21.5
|
22100 nmol*h/L
Geometric Coefficient of Variation 28.7
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1.-0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
Time from last dosing to maximum concentration of the analyte in plasma (tmax) after first dose and at steady-state
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Time to Maximum Concentration of the Analyte in Plasma
tmax after first dose
|
1.50 h
Full Range 27.5 • Interval 0.667 to 1.5
|
1.50 h
Full Range 18.2 • Interval 0.983 to 2.0
|
1.50 h
Full Range 38.5 • Interval 0.983 to 4.0
|
3.00 h
Full Range 77.8 • Interval 0.983 to 4.0
|
—
|
|
Time to Maximum Concentration of the Analyte in Plasma
tmax at steady-state (N=9,8,9,8)
|
1.50 h
Full Range 27.4 • Interval 0.983 to 2.0
|
1.50 h
Full Range 24.3 • Interval 0.983 to 2.0
|
2.00 h
Full Range 62.6 • Interval 0.667 to 4.2
|
1.50 h
Full Range 62.3 • Interval 0.983 to 4.0
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
Terminal rate constant in plasma after first dose and at steady-state
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Terminal Rate Constant in Plasma
Terminal rate at steady-state (N=9,8,9,8)
|
0.0686 1/h
Geometric Coefficient of Variation 18.5
|
0.0491 1/h
Geometric Coefficient of Variation 17.5
|
0.0658 1/h
Geometric Coefficient of Variation 18.8
|
0.0409 1/h
Geometric Coefficient of Variation 48.4
|
—
|
|
Terminal Rate Constant in Plasma
Terminal rate after first dose
|
0.0618 1/h
Geometric Coefficient of Variation 22.4
|
0.0586 1/h
Geometric Coefficient of Variation 11.5
|
0.0654 1/h
Geometric Coefficient of Variation 19.9
|
0.0527 1/h
Geometric Coefficient of Variation 26.8
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK Set
Terminal half life of the analyte in plasma (t1/2) and mean residence time of the analyte in the body after single oral administration (MRTpo) after first dose and at steady-state.
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Half-life and Mean Residence Time of the Analyte in Plasma
t1/2 after first dose
|
11.2 h
Geometric Coefficient of Variation 22.4
|
11.8 h
Geometric Coefficient of Variation 11.5
|
10.6 h
Geometric Coefficient of Variation 19.9
|
13.2 h
Geometric Coefficient of Variation 26.8
|
—
|
|
Half-life and Mean Residence Time of the Analyte in Plasma
t1/2 at steady state (N=9,8,9,8)
|
10.1 h
Geometric Coefficient of Variation 18.5
|
14.1 h
Geometric Coefficient of Variation 17.5
|
10.5 h
Geometric Coefficient of Variation 18.8
|
17.0 h
Geometric Coefficient of Variation 48.4
|
—
|
|
Half-life and Mean Residence Time of the Analyte in Plasma
MRT po after first dose
|
12.2 h
Geometric Coefficient of Variation 12.4
|
12.1 h
Geometric Coefficient of Variation 19.1
|
11.0 h
Geometric Coefficient of Variation 13.5
|
12.7 h
Geometric Coefficient of Variation 19.7
|
—
|
|
Half-life and Mean Residence Time of the Analyte in Plasma
MRT po at steady-state (9,8,9,8)
|
10.7 h
Geometric Coefficient of Variation 14.2
|
13.5 h
Geometric Coefficient of Variation 22.7
|
11.2 h
Geometric Coefficient of Variation 13.7
|
14.6 h
Geometric Coefficient of Variation 20.6
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
Apparent volume of distribution during the terminal phase (Vz/F) after first dose and at steady state. Apparent volume is defined as CL/F divided by the terminal rate constant in plasma (either after first dose or at steady-state).
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase
Vz/F after first dose
|
192 L
Geometric Coefficient of Variation 27.2
|
200 L
Geometric Coefficient of Variation 19.5
|
177 L
Geometric Coefficient of Variation 27.9
|
181 L
Geometric Coefficient of Variation 35.1
|
—
|
|
Apparent Volume of Distribution During the Terminal Phase
Vz/F at steady state (N=9,8,9,8)
|
176 L
Geometric Coefficient of Variation 25.0
|
225 L
Geometric Coefficient of Variation 25.9
|
172 L
Geometric Coefficient of Variation 21.7
|
245 L
Geometric Coefficient of Variation 56.7
|
—
|
SECONDARY outcome
Timeframe: 0-2, 2-4, 4-6, 6-8, 8-12, 12-16, 16-24, 24-36, 36-48 hours (h) after dose on day 1 and 0-2, 2-4, 4-6, 6-8, 8-12, 12-16, 16-24, 24-36, 36-48 and 48-72 hours (h) after dose on day 9Population: PK set
Amount of analyte that is eliminated in urine after first dose and at steady state from the time interval 0 to 24 h (Ae0-24) and 0 to 48 h (Ae0-48)
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Amount of Analyte Eliminated in Urine
Ae0-48 after first dose
|
706 nmol
Geometric Coefficient of Variation 24.7
|
2570 nmol
Geometric Coefficient of Variation 42.2
|
5250 nmol
Geometric Coefficient of Variation 52.0
|
18500 nmol
Geometric Coefficient of Variation 32.7
|
—
|
|
Amount of Analyte Eliminated in Urine
Ae0-48 at steady-state (N=9,8,8,9)
|
941 nmol
Geometric Coefficient of Variation 32.1
|
4530 nmol
Geometric Coefficient of Variation 23.5
|
8450 nmol
Geometric Coefficient of Variation 42.7
|
22400 nmol
Geometric Coefficient of Variation 145
|
—
|
|
Amount of Analyte Eliminated in Urine
Ae0-24 after first dose
|
613 nmol
Geometric Coefficient of Variation 26.9
|
2250 nmol
Geometric Coefficient of Variation 42.7
|
4770 nmol
Geometric Coefficient of Variation 54.6
|
16600 nmol
Geometric Coefficient of Variation 34.3
|
—
|
|
Amount of Analyte Eliminated in Urine
Ae0-24 at steady-state (N=9,8,8,9)
|
820 nmol
Geometric Coefficient of Variation 33.9
|
4040 nmol
Geometric Coefficient of Variation 26.7
|
7520 nmol
Geometric Coefficient of Variation 43.6
|
19300 nmol
Geometric Coefficient of Variation 153
|
—
|
SECONDARY outcome
Timeframe: 0-2, 2-4, 4-6, 6-8, 8-12, 12-16, 16-24, 24-36, 36-48 hours (h) after dose on day 1 and 0-2, 2-4, 4-6, 6-8, 8-12, 12-16, 16-24, 24-36, 36-48 and 48-72 hours (h) after dose on day 9Population: PK set
Fraction of analyte excreted unchanged in urine in the time interval 0 to 12 h (fe0-12) after first dose and at steady-state. The fraction excreted was calculated by dividing Ae0-12 by the Dose and multiply it with 100. Fraction of analyte excreted unchanged in urine in the time interval 0 to 24 h (fe0-24) after first dose and at steady-state. The fraction excreted was calculated by dividing Ae0-24 by the Dose and multiply it with 100.
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Fraction of Analyte Excreted Unchanged in Urine
fe0-24 after first dose
|
11.1 percent of analyte
Geometric Coefficient of Variation 26.9
|
10.1 percent of analyte
Geometric Coefficient of Variation 42.7
|
7.38 percent of analyte
Geometric Coefficient of Variation 73.0
|
7.48 percent of analyte
Geometric Coefficient of Variation 34.3
|
—
|
|
Fraction of Analyte Excreted Unchanged in Urine
fe0-12 after first dose
|
8.50 percent of analyte
Geometric Coefficient of Variation 31.9
|
8.43 percent of analyte
Geometric Coefficient of Variation 39.8
|
6.30 percent of analyte
Geometric Coefficient of Variation 78.2
|
6.17 percent of analyte
Geometric Coefficient of Variation 37.6
|
—
|
|
Fraction of Analyte Excreted Unchanged in Urine
fe0-12 at steady-state (N=9,8,8,9)
|
10.6 percent of analyte
Geometric Coefficient of Variation 47.0
|
14.7 percent of analyte
Geometric Coefficient of Variation 26.5
|
9.22 percent of analyte
Geometric Coefficient of Variation 54.0
|
6.68 percent of analyte
Geometric Coefficient of Variation 154
|
—
|
|
Fraction of Analyte Excreted Unchanged in Urine
fe0-24 at steady-state (N=9,8,8,9)
|
14.8 percent of analyte
Geometric Coefficient of Variation 33.9
|
18.2 percent of analyte
Geometric Coefficient of Variation 26.7
|
11.4 percent of analyte
Geometric Coefficient of Variation 53.6
|
8.71 percent of analyte
Geometric Coefficient of Variation 153
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
Apparent clearance of the analyte in plasma (CL/F) after first dose and at steady-state, Renal clearance of the analyte in plasma after extravascular administration (CLR) after first dose and at steady-state. Apparent clearance after first dose is defined as the dose divided by AUC0-∞; apparent clearance at steady-state is defined as the dose divided by AUC0-tau at steady-state. Renal clearance CLR(0-t) is defined as Ae0-t divided by AUC0-t.
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Apparent and Renal Clearance of the Analyte in Plasma
CL/F after first dose
|
198 mL/min
Geometric Coefficient of Variation 19.6
|
195 mL/min
Geometric Coefficient of Variation 14.7
|
193 mL/min
Geometric Coefficient of Variation 23.7
|
159 mL/min
Geometric Coefficient of Variation 19.4
|
—
|
|
Apparent and Renal Clearance of the Analyte in Plasma
CL/F at steady-state (N=9,8,9,8)
|
201 mL/min
Geometric Coefficient of Variation 24.3
|
184 mL/min
Geometric Coefficient of Variation 17.4
|
189 mL/min
Geometric Coefficient of Variation 21.5
|
167 mL/min
Geometric Coefficient of Variation 28.7
|
—
|
|
Apparent and Renal Clearance of the Analyte in Plasma
CLR (0-48h) after first dose
|
26.7 mL/min
Geometric Coefficient of Variation 42.9
|
23.5 mL/min
Geometric Coefficient of Variation 33.0
|
18.8 mL/min
Geometric Coefficient of Variation 53.1
|
13.9 mL/min
Geometric Coefficient of Variation 44.1
|
—
|
|
Apparent and Renal Clearance of the Analyte in Plasma
CLR (0-24h) at steady-state (N=9,8,8,9)
|
29.7 mL/min
Geometric Coefficient of Variation 52.0
|
33.6 mL/min
Geometric Coefficient of Variation 24.9
|
21.7 mL/min
Geometric Coefficient of Variation 47.1
|
22.2 mL/min
Geometric Coefficient of Variation 83.3
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
Peak trough fluctuation (PTF) is defined as the difference between Cmax and Cmin divided by Cavg and multiplied with 100% at steady-state
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=8 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=8 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Peak Trough Fluctuation
|
323 PTF(%) of Empagliflozin
Geometric Coefficient of Variation 20.6
|
294 PTF(%) of Empagliflozin
Geometric Coefficient of Variation 28.4
|
281 PTF(%) of Empagliflozin
Geometric Coefficient of Variation 26.4
|
265 PTF(%) of Empagliflozin
Geometric Coefficient of Variation 31.9
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
The linearity index is defined as AUC0-tau divided by AUC0-∞ both at steady state.
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=8 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=8 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Linearity Index
|
0.983 Fraction
Geometric Coefficient of Variation 8.42
|
1.05 Fraction
Geometric Coefficient of Variation 2.39
|
1.02 Fraction
Geometric Coefficient of Variation 11.4
|
0.962 Fraction
Geometric Coefficient of Variation 19.7
|
—
|
SECONDARY outcome
Timeframe: -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h and 48h after dose on day 1. -0:05 before dose and 0:10,0:20,0:30,0:40,1h,1:30h,2h,3h,4h,6h,8h,12h,16h,24h,30h,36h, 48h,60h and 72h after dose on day 9.Population: PK set
Accumulation ratio based on Cmax (RA,Cmax) and Accumulated ratio based on AUC0-tau (RA,AUC) at steady-state. Accumulation ratio for the respective doses were calculated using below mentioned equations: RA,Cmax = Cmax,ss/Cmax RA,AUC= AUCtau,ss/AUCtau
Outcome measures
| Measure |
Placebo
n=9 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=8 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=8 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Accumulation Ratios
Accumulation ratio based on Cmax
|
1.09 Ratio
Geometric Coefficient of Variation 27.0
|
1.13 Ratio
Geometric Coefficient of Variation 20.9
|
1.05 Ratio
Geometric Coefficient of Variation 22.3
|
0.972 Ratio
Geometric Coefficient of Variation 36.8
|
—
|
|
Accumulation Ratios
Accumulated ratio based on AUC0-tau
|
1.16 Ratio
Geometric Coefficient of Variation 8.39
|
1.23 Ratio
Geometric Coefficient of Variation 6.17
|
1.16 Ratio
Geometric Coefficient of Variation 11.9
|
1.12 Ratio
Geometric Coefficient of Variation 20.7
|
—
|
SECONDARY outcome
Timeframe: -2-0 hours(h) before drug administration and 0-2, 2-4, 4-6, 6-8, 8-12,12-16 and 16-24 h after drug administration on day -2 and day 8Population: Pharmacodynamic (PD) analysis set (PDS) contains of all patients who received study medication and have evaluable pharmacodynamic parameter data.
Change from baseline to day 8 in urinary glucose excretion. Baseline is defined as Day -2.
Outcome measures
| Measure |
Placebo
n=11 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=8 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Change From Baseline to Day 8 in Urinary Glucose Excretion
|
-3254.43 mg
Standard Deviation 8250.43
|
34638.37 mg
Standard Deviation 16226.22
|
78709.87 mg
Standard Deviation 53463.52
|
74030.40 mg
Standard Deviation 35378.01
|
88040.32 mg
Standard Deviation 20265.87
|
SECONDARY outcome
Timeframe: 0:00, 2:00, 5:00, 7:00, 10:00, 12:00,13:30 and 24:00 hours(h) after drug administration on day -2 and -0.05, 2:30, 5:00, 7:00, 10:00, 12.00, 13:30 and 24:00 hours (h) after drug administration on day 8Population: PDS
Change from baseline to Day 8 in mean daily glucose. Baseline is defined as Day -2.
Outcome measures
| Measure |
Placebo
n=11 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=8 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Mean Daily Glucose
|
-13.85 mg/dL
Standard Deviation 21.39
|
-27.03 mg/dL
Standard Deviation 24.59
|
-34.04 mg/dL
Standard Deviation 19.43
|
-25.89 mg/dL
Standard Deviation 18.00
|
-30.96 mg/dL
Standard Deviation 25.03
|
SECONDARY outcome
Timeframe: -0:30 (Pre dose samples)Population: PDS
Percentage change from baseline to Day 8 in fasting plasma glucose. Baseline is defined as Day -2.
Outcome measures
| Measure |
Placebo
n=11 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=8 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Fasting Plasma Glucose
|
-15.88 percentage of fasting plasma glucose
Standard Deviation 12.88
|
-21.01 percentage of fasting plasma glucose
Standard Deviation 6.38
|
-25.69 percentage of fasting plasma glucose
Standard Deviation 9.88
|
-14.21 percentage of fasting plasma glucose
Standard Deviation 26.00
|
-24.85 percentage of fasting plasma glucose
Standard Deviation 8.18
|
SECONDARY outcome
Timeframe: 0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8Population: PDS
Serum insulin measured for on day -2 and day 8 for AUEC0-5 and AUEC0-12. AUEC0-5: The area under the effect concentration-time curve over the time interval 0 to 5. AUEC0-12: The area under the effect concentration-time curve over the time interval 0 to 12.
Outcome measures
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Serum Insulin
AUEC0-12 (11,9,7,9,8) on day8
|
288 µU*h/mL
Standard Deviation 97.1
|
417 µU*h/mL
Standard Deviation 132
|
387 µU*h/mL
Standard Deviation 154
|
266 µU*h/mL
Standard Deviation 193
|
275 µU*h/mL
Standard Deviation 72.4
|
|
Serum Insulin
AUEC0-5 (12,9,9,9,9) on day-2
|
134 µU*h/mL
Standard Deviation 52.5
|
185 µU*h/mL
Standard Deviation 79.2
|
175 µU*h/mL
Standard Deviation 70.7
|
137 µU*h/mL
Standard Deviation 64.7
|
119 µU*h/mL
Standard Deviation 35.9
|
|
Serum Insulin
AUEC0-12 (12,9,9,9,9) on day-2
|
300 µU*h/mL
Standard Deviation 111
|
474 µU*h/mL
Standard Deviation 149
|
471 µU*h/mL
Standard Deviation 143
|
336 µU*h/mL
Standard Deviation 161
|
282 µU*h/mL
Standard Deviation 41.6
|
|
Serum Insulin
AUEC0-5 (11,9,8,9,9) on day8
|
122 µU*h/mL
Standard Deviation 52.0
|
174 µU*h/mL
Standard Deviation 80.9
|
180 µU*h/mL
Standard Deviation 74.7
|
117 µU*h/mL
Standard Deviation 103
|
101 µU*h/mL
Standard Deviation 37.2
|
SECONDARY outcome
Timeframe: 0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8Population: PDS
Serum insulin measured for on day -2 and day 8 for Emax0-5, Emax0-12, Emin0-5 and Emin0-12. Emax: Maximum effect (maximum measured concentration of glucose or insulin in plasma) \& Emin: Minimum effect (minimum measured concentration of glucose or insulin in plasma)
Outcome measures
| Measure |
Placebo
n=12 Participants
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 Participants
Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 10 mg qd
n=9 Participants
Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 25 mg qd
n=9 Participants
Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
|
Empagliflozin 100 mg qd
n=9 Participants
Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.
|
|---|---|---|---|---|---|
|
Serum Insulin
Emax,0-5 (12,9,9,9,9) on day-2
|
38.1 µU/mL
Standard Deviation 17.3
|
55.2 µU/mL
Standard Deviation 29.9
|
51.2 µU/mL
Standard Deviation 23.4
|
40.2 µU/mL
Standard Deviation 19.4
|
35.2 µU/mL
Standard Deviation 15.5
|
|
Serum Insulin
Emax,0-12 (12,9,9,9,9) on day-2
|
45.4 µU/mL
Standard Deviation 12.6
|
68.5 µU/mL
Standard Deviation 25.3
|
72.1 µU/mL
Standard Deviation 27.7
|
48.7 µU/mL
Standard Deviation 30.9
|
45.3 µU/mL
Standard Deviation 11.3
|
|
Serum Insulin
Emin,0-12 (11,9,8,9,9) on day8
|
7.41 µU/mL
Standard Deviation 3.90
|
8.53 µU/mL
Standard Deviation 3.46
|
10.7 µU/mL
Standard Deviation 5.60
|
5.17 µU/mL
Standard Deviation 3.19
|
3.96 µU/mL
Standard Deviation 2.79
|
|
Serum Insulin
Emin,0-5 (12,9,9,9,9) on day-2
|
10.3 µU/mL
Standard Deviation 5.46
|
14.1 µU/mL
Standard Deviation 5.45
|
13.7 µU/mL
Standard Deviation 4.62
|
9.16 µU/mL
Standard Deviation 7.59
|
7.86 µU/mL
Standard Deviation 2.18
|
|
Serum Insulin
Emin,0-12 (12,9,9,9,9) on day-2
|
9.98 µU/mL
Standard Deviation 4.86
|
14.1 µU/mL
Standard Deviation 5.45
|
13.5 µU/mL
Standard Deviation 4.37
|
9.16 µU/mL
Standard Deviation 7.59
|
7.86 µU/mL
Standard Deviation 2.18
|
|
Serum Insulin
Emax,0-5 (11,9,8,9,9) on day8
|
35.6 µU/mL
Standard Deviation 15.6
|
56.0 µU/mL
Standard Deviation 32.1
|
56.3 µU/mL
Standard Deviation 25.4
|
36.2 µU/mL
Standard Deviation 37.3
|
29.6 µU/mL
Standard Deviation 11.7
|
|
Serum Insulin
Emax,0-12 (11,9,8,9,9) on day8
|
42.6 µU/mL
Standard Deviation 13.1
|
70.2 µU/mL
Standard Deviation 26.1
|
68.6 µU/mL
Standard Deviation 31.1
|
44.4 µU/mL
Standard Deviation 35.5
|
37.3 µU/mL
Standard Deviation 8.10
|
|
Serum Insulin
Emin,0-5 (11,9,8,9,9) on day8
|
7.55 µU/mL
Standard Deviation 3.82
|
8.63 µU/mL
Standard Deviation 3.39
|
10.7 µU/mL
Standard Deviation 5.60
|
5.33 µU/mL
Standard Deviation 3.14
|
3.96 µU/mL
Standard Deviation 2.79
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Empagliflozin 2.5 mg qd
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Empagliflozin 10 mg qd
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Empagliflozin 25 mg qd
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Empagliflozin 100 mg qd
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=12 participants at risk
Patients were treated with matching placebo as tablet once daily in the morning.
|
Empagliflozin 2.5 mg qd
n=9 participants at risk
Patients were treated with 2.5 mg Empagliflozin as tablet once daily in the morning.
|
Empagliflozin 10 mg qd
n=9 participants at risk
Patients were treated with 10 mg Empagliflozin as tablet once daily in the morning.
|
Empagliflozin 25 mg qd
n=9 participants at risk
Patients were treated with 25 mg Empagliflozin as tablet once daily in the morning.
|
Empagliflozin 100 mg qd
n=9 participants at risk
Patients were treated with 100 mg Empagliflozin as tablet once daily in the morning.
|
|---|---|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
|
Infections and infestations
Rhinitis
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
22.2%
2/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
22.2%
2/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/12 • day1 to day21
|
22.2%
2/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Nervous system disorders
Sciatica
|
0.00%
0/12 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Eye disorders
Eye pruritus
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
|
Vascular disorders
Thrombophlebitis
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
1/12 • day1 to day21
|
22.2%
2/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Gastrointestinal disorders
Gastric disorder
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.3%
1/12 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/12 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
General disorders
Injection site thrombosis
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
|
General disorders
Oedema peripheral
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
11.1%
1/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Investigations
Hepatic enzyme increased
|
8.3%
1/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/12 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
22.2%
2/9 • day1 to day21
|
0.00%
0/9 • day1 to day21
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
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