Diabetes Mellitus, Type 2
Conditions
Brief summary
To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 10773 with repeat dosing for eight days and the exploration of the pharmacokinetics and pharmacodynamics of BI 10773 after multiple dosing, including dose proportionality and assessment of steady state.
Interventions
DRUGBI 10773 Placebo
po taken fasting with 240 mL water
DRUGBI 10773
po taken fasting with 240 mL water
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male and postmenopausal or hysterectomised female patients with proven diagnosis of type 2 diabetes mellitus treated with diet and exercise only or on a maximum of two oral antidiabetic agents except thiazolidindiones with at least one agent taken at 50% of its maximum dose or less. 2. Glycosylated haemoglobin A1 (HbA1c) £ 8.5 % at screening. 3. Age \>21 and Age \<70 years (male and hysterectomised female patients) Age \>60 and Age \<70 years (postmenopausal female patients) 4. Body Mass Index (BMI) \>18.5 and \<40 kg/m2 5. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
Exclusion criteria
1. Antidiabetic treatment with insulin or glitazones or with more than one oral hypoglycaemic agent (except if 2 agents and at least one of them not taken at more than 50% of its maximum dose) 2. Fasted blood glucose \> 240 mg/dl (\>13.3 mmol/L) on two consecutive days during washout. 3. Glycosylated haemoglobin A1 (HbA1c) \>8.5% at screening 4. Clinically relevant concomitant diseases other than type 2 diabetes, hyperlipidaemia and medically treated hypertension, such as: * Any late stage complication of diabetes (e.g. retinopathy, polyneuropathy, vegetative disorders, diabetic foot) * Renal insufficiency (calculated creatinine clearance \< 80 ml/min/1.73m²) * Cardiac insufficiency NYHA II-IV, myocardial infarction, other known cardiovascular diseases including hypertension \> 160/95mmHg (measured at training visit and each of the timepoints of Day -1), stroke and TIA (Transistoric ischaemic attack) * Neurological disorders (such as epilepsy) or psychiatric disorders * Acute or relevant chronic infections (e.g. HIV, repeated urogenital infections) * Any gastrointestinal, hepatic, respiratory, endocrine or immunological disorder 5. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 6. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms) 7. A history of additional risk factors for TdP (torsade des pointes) (e.g., heart failure, hypokalemia, family history of sudden death before the age of 50)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | day 1 to day 21 | 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). |
| Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | day 1 to day 21 | Percentage of participants with clinically relevant findings in electrocardiogram (ECG) results |
| Micturition Frequency | Baseline and Day 9 | 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. |
| Assessment of Tolerability by Investigator | day 21 | Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Half-life and Mean Residence Time of the Analyte in Plasma | -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. | 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. |
| Apparent Volume of Distribution During the Terminal Phase | -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. | 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). |
| Amount of Analyte Eliminated in Urine | 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 9 | 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) |
| Fraction of Analyte Excreted Unchanged in Urine | 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 9 | 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. |
| Apparent and Renal Clearance of the Analyte in Plasma | -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. | 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. |
| Peak Trough Fluctuation | -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. | Peak trough fluctuation (PTF) is defined as the difference between Cmax and Cmin divided by Cavg and multiplied with 100% at steady-state |
| Concentration of the Analyte in Plasma | -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. | 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) |
| Accumulation Ratios | -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. | 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 |
| Change From Baseline to Day 8 in Urinary Glucose Excretion | -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 8 | Change from baseline to day 8 in urinary glucose excretion. Baseline is defined as Day -2. |
| Mean Daily Glucose | 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 8 | Change from baseline to Day 8 in mean daily glucose. Baseline is defined as Day -2. |
| Fasting Plasma Glucose | -0:30 (Pre dose samples) | Percentage change from baseline to Day 8 in fasting plasma glucose. Baseline is defined as Day -2. |
| Serum Insulin | 0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8 | 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. |
| Linearity Index | -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. | The linearity index is defined as AUC0-tau divided by AUC0-∞ both at steady state. |
| Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | -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. | 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. |
| Time to Maximum Concentration of the Analyte in Plasma | -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. | Time from last dosing to maximum concentration of the analyte in plasma (tmax) after first dose and at steady-state |
| Terminal Rate Constant in Plasma | -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. | Terminal rate constant in plasma after first dose and at steady-state |
Countries
Germany
Participant flow
Recruitment details
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.
Pre-assignment details
14 days wash-out of previous antidiabetic therapy followed by 8 days of once daily dosing at each dose level.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients were treated with matching placebo as tablet once daily in the morning. | 12 |
| Empagliflozin 2.5 mg qd Patients were treated with 2.5 mg Empagliflozin as tablet once daily in the morning. | 9 |
| Empagliflozin 10 mg qd Patients were treated with 10 mg Empagliflozin as tablet once daily in the morning. | 9 |
| Empagliflozin 25 mg qd Patients were treated with 25 mg Empagliflozin as tablet once daily in the morning. | 9 |
| Empagliflozin 100 mg qd Patients were treated with 100 mg Empagliflozin as tablet once daily in the morning. | 9 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Empagliflozin 2.5 mg qd | Empagliflozin 10 mg qd | Empagliflozin 25 mg qd | Empagliflozin 100 mg qd | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 6.4 | 53.9 years STANDARD_DEVIATION 10.9 | 51.8 years STANDARD_DEVIATION 10.7 | 58.9 years STANDARD_DEVIATION 8.8 | 60.3 years STANDARD_DEVIATION 5.6 | 56.9 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 8 Participants | 7 Participants | 7 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 6 / 9 | 5 / 9 | 5 / 9 | 3 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Assessment of Tolerability by Investigator
Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad.
Time frame: day 21
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Assessment of Tolerability by Investigator | Not satisfactory | 0.0 percentage of participants |
| Placebo | Assessment of Tolerability by Investigator | Good | 91.7 percentage of participants |
| Placebo | Assessment of Tolerability by Investigator | Bad | 8.3 percentage of participants |
| Placebo | Assessment of Tolerability by Investigator | Satisfactory | 0.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Assessment of Tolerability by Investigator | Good | 100.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Assessment of Tolerability by Investigator | Bad | 0.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Assessment of Tolerability by Investigator | Satisfactory | 0.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Assessment of Tolerability by Investigator | Not satisfactory | 0.0 percentage of participants |
| Empagliflozin 10 mg qd | Assessment of Tolerability by Investigator | Satisfactory | 0.0 percentage of participants |
| Empagliflozin 10 mg qd | Assessment of Tolerability by Investigator | Bad | 0.0 percentage of participants |
| Empagliflozin 10 mg qd | Assessment of Tolerability by Investigator | Good | 100.0 percentage of participants |
| Empagliflozin 10 mg qd | Assessment of Tolerability by Investigator | Not satisfactory | 0.0 percentage of participants |
| Empagliflozin 25 mg qd | Assessment of Tolerability by Investigator | Satisfactory | 0.0 percentage of participants |
| Empagliflozin 25 mg qd | Assessment of Tolerability by Investigator | Good | 100.0 percentage of participants |
| Empagliflozin 25 mg qd | Assessment of Tolerability by Investigator | Not satisfactory | 0.0 percentage of participants |
| Empagliflozin 25 mg qd | Assessment of Tolerability by Investigator | Bad | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Assessment of Tolerability by Investigator | Not satisfactory | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Assessment of Tolerability by Investigator | Good | 100.0 percentage of participants |
| Empagliflozin 100 mg qd | Assessment of Tolerability by Investigator | Satisfactory | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Assessment of Tolerability by Investigator | Bad | 0.0 percentage of participants |
Primary
Micturition Frequency
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.
Time frame: Baseline and Day 9
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Micturition Frequency | Micturition night frequency | 0.3 frequency of micturition | Standard Deviation 1.6 |
| Placebo | Micturition Frequency | Micturition total frequency | 4.5 frequency of micturition | Standard Deviation 2.1 |
| Placebo | Micturition Frequency | Micturition day frequency | 4.1 frequency of micturition | Standard Deviation 1.8 |
| Empagliflozin 2.5 mg qd | Micturition Frequency | Micturition total frequency | 2.8 frequency of micturition | Standard Deviation 2.6 |
| Empagliflozin 2.5 mg qd | Micturition Frequency | Micturition day frequency | 2.6 frequency of micturition | Standard Deviation 2.1 |
| Empagliflozin 2.5 mg qd | Micturition Frequency | Micturition night frequency | 0.2 frequency of micturition | Standard Deviation 1.2 |
| Empagliflozin 10 mg qd | Micturition Frequency | Micturition total frequency | 5.5 frequency of micturition | Standard Deviation 1.5 |
| Empagliflozin 10 mg qd | Micturition Frequency | Micturition day frequency | 5.0 frequency of micturition | Standard Deviation 1.6 |
| Empagliflozin 10 mg qd | Micturition Frequency | Micturition night frequency | 0.5 frequency of micturition | Standard Deviation 0.5 |
| Empagliflozin 25 mg qd | Micturition Frequency | Micturition day frequency | 3.9 frequency of micturition | Standard Deviation 1.5 |
| Empagliflozin 25 mg qd | Micturition Frequency | Micturition night frequency | 0.6 frequency of micturition | Standard Deviation 1.6 |
| Empagliflozin 25 mg qd | Micturition Frequency | Micturition total frequency | 4.4 frequency of micturition | Standard Deviation 2.4 |
| Empagliflozin 100 mg qd | Micturition Frequency | Micturition night frequency | 0.7 frequency of micturition | Standard Deviation 0.9 |
| Empagliflozin 100 mg qd | Micturition Frequency | Micturition total frequency | 5.1 frequency of micturition | Standard Deviation 2.2 |
| Empagliflozin 100 mg qd | Micturition Frequency | Micturition day frequency | 4.4 frequency of micturition | Standard Deviation 2.1 |
Primary
Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results
Percentage of participants with clinically relevant findings in electrocardiogram (ECG) results
Time frame: day 1 to day 21
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically relevant | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically irrelevant | 100.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically relevant | 0.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically irrelevant | 100.0 percentage of participants |
| Empagliflozin 10 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically relevant | 0.0 percentage of participants |
| Empagliflozin 10 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically irrelevant | 100.0 percentage of participants |
| Empagliflozin 25 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically irrelevant | 100.0 percentage of participants |
| Empagliflozin 25 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically relevant | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically relevant | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results | Clinically irrelevant | 100.0 percentage of participants |
Primary
Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests
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).
Time frame: day 1 to day 21
Population: Treated set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Cardiac disorders | 0.0 percentage of participants |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Cardiac disorders | 0.0 percentage of participants |
| Empagliflozin 2.5 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Investigations: Hepatic enzyme increased | 0.0 percentage of participants |
| Empagliflozin 10 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Cardiac disorders | 0.0 percentage of participants |
| Empagliflozin 10 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Investigations: Hepatic enzyme increased | 0.0 percentage of participants |
| Empagliflozin 25 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Investigations: Hepatic enzyme increased | 0.0 percentage of participants |
| Empagliflozin 25 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Cardiac disorders | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Cardiac disorders | 0.0 percentage of participants |
| Empagliflozin 100 mg qd | Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests | Investigations: Hepatic enzyme increased | 0.0 percentage of participants |
Secondary
Accumulation Ratios
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
Time frame: -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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Accumulation Ratios | Accumulation ratio based on Cmax | 1.09 Ratio | Geometric Coefficient of Variation 27 |
| Placebo | Accumulation Ratios | Accumulated ratio based on AUC0-tau | 1.16 Ratio | Geometric Coefficient of Variation 8.39 |
| Empagliflozin 2.5 mg qd | Accumulation Ratios | Accumulated ratio based on AUC0-tau | 1.23 Ratio | Geometric Coefficient of Variation 6.17 |
| Empagliflozin 2.5 mg qd | Accumulation Ratios | Accumulation ratio based on Cmax | 1.13 Ratio | Geometric Coefficient of Variation 20.9 |
| Empagliflozin 10 mg qd | Accumulation Ratios | Accumulation ratio based on Cmax | 1.05 Ratio | Geometric Coefficient of Variation 22.3 |
| Empagliflozin 10 mg qd | Accumulation Ratios | Accumulated ratio based on AUC0-tau | 1.16 Ratio | Geometric Coefficient of Variation 11.9 |
| Empagliflozin 25 mg qd | Accumulation Ratios | Accumulation ratio based on Cmax | 0.972 Ratio | Geometric Coefficient of Variation 36.8 |
| Empagliflozin 25 mg qd | Accumulation Ratios | Accumulated ratio based on AUC0-tau | 1.12 Ratio | Geometric Coefficient of Variation 20.7 |
Secondary
Amount of Analyte Eliminated in Urine
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)
Time frame: 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 9
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Amount of Analyte Eliminated in Urine | Ae0-24 at steady-state (N=9,8,8,9) | 820 nmol | Geometric Coefficient of Variation 33.9 |
| Placebo | Amount of Analyte Eliminated in Urine | Ae0-48 at steady-state (N=9,8,8,9) | 941 nmol | Geometric Coefficient of Variation 32.1 |
| Placebo | Amount of Analyte Eliminated in Urine | Ae0-24 after first dose | 613 nmol | Geometric Coefficient of Variation 26.9 |
| Placebo | Amount of Analyte Eliminated in Urine | Ae0-48 after first dose | 706 nmol | Geometric Coefficient of Variation 24.7 |
| Empagliflozin 2.5 mg qd | Amount of Analyte Eliminated in Urine | Ae0-48 at steady-state (N=9,8,8,9) | 4530 nmol | Geometric Coefficient of Variation 23.5 |
| Empagliflozin 2.5 mg qd | Amount of Analyte Eliminated in Urine | Ae0-48 after first dose | 2570 nmol | Geometric Coefficient of Variation 42.2 |
| Empagliflozin 2.5 mg qd | Amount of Analyte Eliminated in Urine | Ae0-24 at steady-state (N=9,8,8,9) | 4040 nmol | Geometric Coefficient of Variation 26.7 |
| Empagliflozin 2.5 mg qd | Amount of Analyte Eliminated in Urine | Ae0-24 after first dose | 2250 nmol | Geometric Coefficient of Variation 42.7 |
| Empagliflozin 10 mg qd | Amount of Analyte Eliminated in Urine | Ae0-48 after first dose | 5250 nmol | Geometric Coefficient of Variation 52 |
| Empagliflozin 10 mg qd | Amount of Analyte Eliminated in Urine | Ae0-48 at steady-state (N=9,8,8,9) | 8450 nmol | Geometric Coefficient of Variation 42.7 |
| Empagliflozin 10 mg qd | Amount of Analyte Eliminated in Urine | Ae0-24 at steady-state (N=9,8,8,9) | 7520 nmol | Geometric Coefficient of Variation 43.6 |
| Empagliflozin 10 mg qd | Amount of Analyte Eliminated in Urine | Ae0-24 after first dose | 4770 nmol | Geometric Coefficient of Variation 54.6 |
| Empagliflozin 25 mg qd | Amount of Analyte Eliminated in Urine | Ae0-48 after first dose | 18500 nmol | Geometric Coefficient of Variation 32.7 |
| Empagliflozin 25 mg qd | Amount of Analyte Eliminated in Urine | Ae0-24 after first dose | 16600 nmol | Geometric Coefficient of Variation 34.3 |
| Empagliflozin 25 mg qd | Amount of Analyte Eliminated in Urine | Ae0-48 at steady-state (N=9,8,8,9) | 22400 nmol | Geometric Coefficient of Variation 145 |
| Empagliflozin 25 mg qd | Amount of Analyte Eliminated in Urine | Ae0-24 at steady-state (N=9,8,8,9) | 19300 nmol | Geometric Coefficient of Variation 153 |
Secondary
Apparent and Renal Clearance of the Analyte in Plasma
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.
Time frame: -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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apparent and Renal Clearance of the Analyte in Plasma | CL/F after first dose | 198 mL/min | Geometric Coefficient of Variation 19.6 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CL/F at steady-state (N=9,8,9,8) | 184 mL/min | Geometric Coefficient of Variation 17.4 |
| Empagliflozin 2.5 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CLR (0-48h) after first dose | 23.5 mL/min | Geometric Coefficient of Variation 33 |
| Empagliflozin 2.5 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CL/F after first dose | 195 mL/min | Geometric Coefficient of Variation 14.7 |
| Empagliflozin 2.5 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CLR (0-24h) at steady-state (N=9,8,8,9) | 33.6 mL/min | Geometric Coefficient of Variation 24.9 |
| Empagliflozin 10 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CL/F at steady-state (N=9,8,9,8) | 189 mL/min | Geometric Coefficient of Variation 21.5 |
| Empagliflozin 10 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CL/F after first dose | 193 mL/min | Geometric Coefficient of Variation 23.7 |
| Empagliflozin 10 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CLR (0-48h) after first dose | 18.8 mL/min | Geometric Coefficient of Variation 53.1 |
| Empagliflozin 10 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CLR (0-24h) at steady-state (N=9,8,8,9) | 21.7 mL/min | Geometric Coefficient of Variation 47.1 |
| Empagliflozin 25 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CL/F at steady-state (N=9,8,9,8) | 167 mL/min | Geometric Coefficient of Variation 28.7 |
| Empagliflozin 25 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CL/F after first dose | 159 mL/min | Geometric Coefficient of Variation 19.4 |
| Empagliflozin 25 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CLR (0-24h) at steady-state (N=9,8,8,9) | 22.2 mL/min | Geometric Coefficient of Variation 83.3 |
| Empagliflozin 25 mg qd | Apparent and Renal Clearance of the Analyte in Plasma | CLR (0-48h) after first dose | 13.9 mL/min | Geometric Coefficient of Variation 44.1 |
Secondary
Apparent Volume of Distribution During the Terminal Phase
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).
Time frame: -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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Apparent Volume of Distribution During the Terminal Phase | Vz/F after first dose | 192 L | Geometric Coefficient of Variation 27.2 |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Apparent Volume of Distribution During the Terminal Phase | Vz/F at steady state (N=9,8,9,8) | 225 L | Geometric Coefficient of Variation 25.9 |
| Empagliflozin 2.5 mg qd | Apparent Volume of Distribution During the Terminal Phase | Vz/F after first dose | 200 L | Geometric Coefficient of Variation 19.5 |
| Empagliflozin 10 mg qd | Apparent Volume of Distribution During the Terminal Phase | Vz/F after first dose | 177 L | Geometric Coefficient of Variation 27.9 |
| Empagliflozin 10 mg qd | Apparent Volume of Distribution During the Terminal Phase | Vz/F at steady state (N=9,8,9,8) | 172 L | Geometric Coefficient of Variation 21.7 |
| Empagliflozin 25 mg qd | Apparent Volume of Distribution During the Terminal Phase | Vz/F after first dose | 181 L | Geometric Coefficient of Variation 35.1 |
| Empagliflozin 25 mg qd | Apparent Volume of Distribution During the Terminal Phase | Vz/F at steady state (N=9,8,9,8) | 245 L | Geometric Coefficient of Variation 56.7 |
Secondary
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC)
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.
Time frame: -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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | AUC0-24 after first dose | 1620 nmol*h/L | Geometric Coefficient of Variation 13.5 |
| Empagliflozin 2.5 mg qd | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | AUC0-∞ after first dose | 1890 nmol*h/L | Geometric Coefficient of Variation 14.7 |
| Empagliflozin 2.5 mg qd | 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) | 2000 nmol*h/L | Geometric Coefficient of Variation 17.4 |
| Empagliflozin 10 mg qd | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | AUC0-24 after first dose | 4200 nmol*h/L | Geometric Coefficient of Variation 23.6 |
| Empagliflozin 10 mg qd | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | AUC0-∞ after first dose | 4780 nmol*h/L | Geometric Coefficient of Variation 23.7 |
| Empagliflozin 10 mg qd | 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) | 4890 nmol*h/L | Geometric Coefficient of Variation 21.5 |
| Empagliflozin 25 mg qd | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | AUC0-∞ after first dose | 23300 nmol*h/L | Geometric Coefficient of Variation 19.4 |
| Empagliflozin 25 mg qd | 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) | 22100 nmol*h/L | Geometric Coefficient of Variation 28.7 |
| Empagliflozin 25 mg qd | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) | AUC0-24 after first dose | 19700 nmol*h/L | Geometric Coefficient of Variation 17.6 |
Comparison: This was non-confirmatory testing, dose proportionality of dose from 2.5mg to 100mg for AUC (0-infinity, single dose) was analysed.95% CI: [33.49, 73.776]Regression, Linear
Comparison: This was non confirmatory testing, dose proportionality of dose from 2.5mg to 100mg for AUC (0-infinity, at steady state, day 9) was analysed.95% CI: [15.429, 91.789]Regression, Linear
Secondary
Change From Baseline to Day 8 in Urinary Glucose Excretion
Change from baseline to day 8 in urinary glucose excretion. Baseline is defined as Day -2.
Time frame: -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 8
Population: Pharmacodynamic (PD) analysis set (PDS) contains of all patients who received study medication and have evaluable pharmacodynamic parameter data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Day 8 in Urinary Glucose Excretion | -3254.43 mg | Standard Deviation 8250.43 |
| Empagliflozin 2.5 mg qd | Change From Baseline to Day 8 in Urinary Glucose Excretion | 34638.37 mg | Standard Deviation 16226.22 |
| Empagliflozin 10 mg qd | Change From Baseline to Day 8 in Urinary Glucose Excretion | 78709.87 mg | Standard Deviation 53463.52 |
| Empagliflozin 25 mg qd | Change From Baseline to Day 8 in Urinary Glucose Excretion | 74030.40 mg | Standard Deviation 35378.01 |
| Empagliflozin 100 mg qd | Change From Baseline to Day 8 in Urinary Glucose Excretion | 88040.32 mg | Standard Deviation 20265.87 |
Comparison: The mean change from baseline (day -2) to day 8 and comparisons to placebo for Urine Glucose Excretion (AE(0-24)).p-value: 0.006795% CI: [11021.57, 64269.3]ANCOVA
Comparison: The mean change from baseline (day -2) to day 8 and comparisons to placebo for Urine Glucose Excretion (AE(0-24)).p-value: <0.000195% CI: [55344.83, 110451.6]ANCOVA
Comparison: The mean change from baseline (day -2) to day 8 and comparisons to placebo for Urine Glucose Excretion (AE(0-24)).p-value: <0.000195% CI: [53087.22, 106878.6]ANCOVA
Comparison: The mean change from baseline (day -2) to day 8 and comparisons to placebo for Urine Glucose Excretion (AE(0-24)).p-value: <0.000195% CI: [64685.41, 117928.5]ANCOVA
Secondary
Concentration of the Analyte in Plasma
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)
Time frame: -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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Concentration of the Analyte in Plasma | C24,8 (N=9,8,9,8) | 4.55 nmol/L | Geometric Coefficient of Variation 36.8 |
| Placebo | 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 |
| Placebo | Concentration of the Analyte in Plasma | Cmax after first dose | 61.3 nmol/L | Geometric Coefficient of Variation 20.5 |
| Empagliflozin 2.5 mg qd | Concentration of the Analyte in Plasma | Cmin at steady-state (N=9,8,9,8) | 23.5 nmol/L | Geometric Coefficient of Variation 31.5 |
| Empagliflozin 2.5 mg qd | Concentration of the Analyte in Plasma | Cavg at steady-state (N=9,8,9,8) | 83.5 nmol/L | Geometric Coefficient of Variation 17.4 |
| Empagliflozin 2.5 mg qd | Concentration of the Analyte in Plasma | C24,8 (N=9,8,9,8) | 23.8 nmol/L | Geometric Coefficient of Variation 31.7 |
| Empagliflozin 2.5 mg qd | Concentration of the Analyte in Plasma | Cmax at steady-state (N=9,8,9,8) | 272 nmol/L | Geometric Coefficient of Variation 30.1 |
| Empagliflozin 2.5 mg qd | Concentration of the Analyte in Plasma | Cmax after first dose | 240 nmol/L | Geometric Coefficient of Variation 21.2 |
| Empagliflozin 10 mg qd | Concentration of the Analyte in Plasma | Cmin at steady-state (N=9,8,9,8) | 47.1 nmol/L | Geometric Coefficient of Variation 35.3 |
| Empagliflozin 10 mg qd | Concentration of the Analyte in Plasma | Cmax after first dose | 592 nmol/L | Geometric Coefficient of Variation 23.7 |
| Empagliflozin 10 mg qd | Concentration of the Analyte in Plasma | Cmax at steady-state (N=9,8,9,8) | 622 nmol/L | Geometric Coefficient of Variation 17.4 |
| Empagliflozin 10 mg qd | Concentration of the Analyte in Plasma | Cavg at steady-state (N=9,8,9,8) | 204 nmol/L | Geometric Coefficient of Variation 21.5 |
| Empagliflozin 10 mg qd | Concentration of the Analyte in Plasma | C24,8 (N=9,8,9,8) | 47.2 nmol/L | Geometric Coefficient of Variation 35.2 |
| Empagliflozin 25 mg qd | Concentration of the Analyte in Plasma | Cavg at steady-state (N=9,8,9,8) | 922 nmol/L | Geometric Coefficient of Variation 28.7 |
| Empagliflozin 25 mg qd | Concentration of the Analyte in Plasma | Cmax at steady-state (N=9,8,9,8) | 2700 nmol/L | Geometric Coefficient of Variation 20.9 |
| Empagliflozin 25 mg qd | Concentration of the Analyte in Plasma | Cmax after first dose | 2670 nmol/L | Geometric Coefficient of Variation 26.1 |
| Empagliflozin 25 mg qd | Concentration of the Analyte in Plasma | Cmin at steady-state (N=9,8,9,8) | 243 nmol/L | Geometric Coefficient of Variation 32 |
| Empagliflozin 25 mg qd | Concentration of the Analyte in Plasma | C24,8 (N=9,8,9,8) | 249 nmol/L | Geometric Coefficient of Variation 27.6 |
Comparison: This was non-confirmatory testing, dose proportionality of dose from 2.5mg to 100mg for Cmax (single dose) was analysed.95% CI: [27.52, 69.269]Regression, Linear
Comparison: This was non-confirmatory testing, dose proportionality of dose from 2.5mg to 100mg for Cmax,ss (Multiple dose) was analysed.95% CI: [12.193, 80.011]Regression, Linear
Secondary
Fasting Plasma Glucose
Percentage change from baseline to Day 8 in fasting plasma glucose. Baseline is defined as Day -2.
Time frame: -0:30 (Pre dose samples)
Population: PDS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Fasting Plasma Glucose | -15.88 percentage of fasting plasma glucose | Standard Deviation 12.88 |
| Empagliflozin 2.5 mg qd | Fasting Plasma Glucose | -21.01 percentage of fasting plasma glucose | Standard Deviation 6.38 |
| Empagliflozin 10 mg qd | Fasting Plasma Glucose | -25.69 percentage of fasting plasma glucose | Standard Deviation 9.88 |
| Empagliflozin 25 mg qd | Fasting Plasma Glucose | -14.21 percentage of fasting plasma glucose | Standard Deviation 26 |
| Empagliflozin 100 mg qd | Fasting Plasma Glucose | -24.85 percentage of fasting plasma glucose | Standard Deviation 8.18 |
Comparison: The mean percent change in Fasting Plasma Glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.223995% CI: [-19.162, 4.624]ANCOVA
Comparison: The mean percent change in Fasting Plasma Glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.042195% CI: [-25.205, -0.484]ANCOVA
Comparison: The mean percent change in Fasting Plasma Glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.652795% CI: [-14.842, 9.403]ANCOVA
Comparison: The mean percent change in Fasting Plasma Glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.131895% CI: [-20.818, 2.822]ANCOVA
Secondary
Fraction of Analyte Excreted Unchanged in Urine
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.
Time frame: 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 9
Population: PK set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 after first dose | 8.50 percent of analyte | Geometric Coefficient of Variation 31.9 |
| Placebo | 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 |
| Placebo | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 after first dose | 11.1 percent of analyte | Geometric Coefficient of Variation 26.9 |
| Empagliflozin 2.5 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 after first dose | 8.43 percent of analyte | Geometric Coefficient of Variation 39.8 |
| Empagliflozin 2.5 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 at steady-state (N=9,8,8,9) | 14.7 percent of analyte | Geometric Coefficient of Variation 26.5 |
| Empagliflozin 2.5 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 after first dose | 10.1 percent of analyte | Geometric Coefficient of Variation 42.7 |
| Empagliflozin 2.5 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 at steady-state (N=9,8,8,9) | 18.2 percent of analyte | Geometric Coefficient of Variation 26.7 |
| Empagliflozin 10 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 after first dose | 7.38 percent of analyte | Geometric Coefficient of Variation 73 |
| Empagliflozin 10 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 at steady-state (N=9,8,8,9) | 11.4 percent of analyte | Geometric Coefficient of Variation 53.6 |
| Empagliflozin 10 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 at steady-state (N=9,8,8,9) | 9.22 percent of analyte | Geometric Coefficient of Variation 54 |
| Empagliflozin 10 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 after first dose | 6.30 percent of analyte | Geometric Coefficient of Variation 78.2 |
| Empagliflozin 25 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 at steady-state (N=9,8,8,9) | 6.68 percent of analyte | Geometric Coefficient of Variation 154 |
| Empagliflozin 25 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 at steady-state (N=9,8,8,9) | 8.71 percent of analyte | Geometric Coefficient of Variation 153 |
| Empagliflozin 25 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-24 after first dose | 7.48 percent of analyte | Geometric Coefficient of Variation 34.3 |
| Empagliflozin 25 mg qd | Fraction of Analyte Excreted Unchanged in Urine | fe0-12 after first dose | 6.17 percent of analyte | Geometric Coefficient of Variation 37.6 |
Secondary
Half-life and Mean Residence Time of the Analyte in Plasma
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.
Time frame: -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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | t1/2 at steady state (N=9,8,9,8) | 14.1 h | Geometric Coefficient of Variation 17.5 |
| Empagliflozin 2.5 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | MRT po at steady-state (9,8,9,8) | 13.5 h | Geometric Coefficient of Variation 22.7 |
| Empagliflozin 2.5 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | t1/2 after first dose | 11.8 h | Geometric Coefficient of Variation 11.5 |
| Empagliflozin 2.5 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | MRT po after first dose | 12.1 h | Geometric Coefficient of Variation 19.1 |
| Empagliflozin 10 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | t1/2 at steady state (N=9,8,9,8) | 10.5 h | Geometric Coefficient of Variation 18.8 |
| Empagliflozin 10 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | MRT po at steady-state (9,8,9,8) | 11.2 h | Geometric Coefficient of Variation 13.7 |
| Empagliflozin 10 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | MRT po after first dose | 11.0 h | Geometric Coefficient of Variation 13.5 |
| Empagliflozin 10 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | t1/2 after first dose | 10.6 h | Geometric Coefficient of Variation 19.9 |
| Empagliflozin 25 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | MRT po at steady-state (9,8,9,8) | 14.6 h | Geometric Coefficient of Variation 20.6 |
| Empagliflozin 25 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | t1/2 at steady state (N=9,8,9,8) | 17.0 h | Geometric Coefficient of Variation 48.4 |
| Empagliflozin 25 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | MRT po after first dose | 12.7 h | Geometric Coefficient of Variation 19.7 |
| Empagliflozin 25 mg qd | Half-life and Mean Residence Time of the Analyte in Plasma | t1/2 after first dose | 13.2 h | Geometric Coefficient of Variation 26.8 |
Secondary
Linearity Index
The linearity index is defined as AUC0-tau divided by AUC0-∞ both at steady state.
Time frame: -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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Linearity Index | 0.983 Fraction | Geometric Coefficient of Variation 8.42 |
| Empagliflozin 2.5 mg qd | Linearity Index | 1.05 Fraction | Geometric Coefficient of Variation 2.39 |
| Empagliflozin 10 mg qd | Linearity Index | 1.02 Fraction | Geometric Coefficient of Variation 11.4 |
| Empagliflozin 25 mg qd | Linearity Index | 0.962 Fraction | Geometric Coefficient of Variation 19.7 |
Secondary
Mean Daily Glucose
Change from baseline to Day 8 in mean daily glucose. Baseline is defined as Day -2.
Time frame: 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 8
Population: PDS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Daily Glucose | -13.85 mg/dL | Standard Deviation 21.39 |
| Empagliflozin 2.5 mg qd | Mean Daily Glucose | -27.03 mg/dL | Standard Deviation 24.59 |
| Empagliflozin 10 mg qd | Mean Daily Glucose | -34.04 mg/dL | Standard Deviation 19.43 |
| Empagliflozin 25 mg qd | Mean Daily Glucose | -25.89 mg/dL | Standard Deviation 18 |
| Empagliflozin 100 mg qd | Mean Daily Glucose | -30.96 mg/dL | Standard Deviation 25.03 |
Comparison: The mean percent decrease in Mean daily glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.044995% CI: [-30.543, -0.369]ANCOVA
Comparison: The mean percent decrease in Mean daily glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.004295% CI: [-39.085, -7.848]ANCOVA
Comparison: The mean percent decrease in Mean daily glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.052195% CI: [-30.057, 0.145]ANCOVA
Comparison: The mean percent decrease in Mean daily glucose from baseline with treatment compared with placebo from baseline -2 to day 8p-value: 0.167695% CI: [-25.848, 4.644]ANCOVA
Secondary
Peak Trough Fluctuation
Peak trough fluctuation (PTF) is defined as the difference between Cmax and Cmin divided by Cavg and multiplied with 100% at steady-state
Time frame: -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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak Trough Fluctuation | 323 PTF(%) of Empagliflozin | Geometric Coefficient of Variation 20.6 |
| Empagliflozin 2.5 mg qd | Peak Trough Fluctuation | 294 PTF(%) of Empagliflozin | Geometric Coefficient of Variation 28.4 |
| Empagliflozin 10 mg qd | Peak Trough Fluctuation | 281 PTF(%) of Empagliflozin | Geometric Coefficient of Variation 26.4 |
| Empagliflozin 25 mg qd | Peak Trough Fluctuation | 265 PTF(%) of Empagliflozin | Geometric Coefficient of Variation 31.9 |
Secondary
Serum Insulin
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)
Time frame: 0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8
Population: PDS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Insulin | Emax,0-12 (11,9,8,9,9) on day8 | 42.6 µU/mL | Standard Deviation 13.1 |
| Placebo | Serum Insulin | Emin,0-12 (11,9,8,9,9) on day8 | 7.41 µU/mL | Standard Deviation 3.9 |
| Placebo | Serum Insulin | Emax,0-5 (12,9,9,9,9) on day-2 | 38.1 µU/mL | Standard Deviation 17.3 |
| Placebo | Serum Insulin | Emax,0-12 (12,9,9,9,9) on day-2 | 45.4 µU/mL | Standard Deviation 12.6 |
| Placebo | Serum Insulin | Emax,0-5 (11,9,8,9,9) on day8 | 35.6 µU/mL | Standard Deviation 15.6 |
| Placebo | Serum Insulin | Emin,0-5 (12,9,9,9,9) on day-2 | 10.3 µU/mL | Standard Deviation 5.46 |
| Placebo | Serum Insulin | Emin,0-5 (11,9,8,9,9) on day8 | 7.55 µU/mL | Standard Deviation 3.82 |
| Placebo | Serum Insulin | Emin,0-12 (12,9,9,9,9) on day-2 | 9.98 µU/mL | Standard Deviation 4.86 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emin,0-12 (12,9,9,9,9) on day-2 | 14.1 µU/mL | Standard Deviation 5.45 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emax,0-12 (12,9,9,9,9) on day-2 | 68.5 µU/mL | Standard Deviation 25.3 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emax,0-5 (11,9,8,9,9) on day8 | 56.0 µU/mL | Standard Deviation 32.1 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emin,0-5 (11,9,8,9,9) on day8 | 8.63 µU/mL | Standard Deviation 3.39 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emax,0-5 (12,9,9,9,9) on day-2 | 55.2 µU/mL | Standard Deviation 29.9 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emin,0-12 (11,9,8,9,9) on day8 | 8.53 µU/mL | Standard Deviation 3.46 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emax,0-12 (11,9,8,9,9) on day8 | 70.2 µU/mL | Standard Deviation 26.1 |
| Empagliflozin 2.5 mg qd | Serum Insulin | Emin,0-5 (12,9,9,9,9) on day-2 | 14.1 µU/mL | Standard Deviation 5.45 |
| Empagliflozin 10 mg qd | Serum Insulin | Emin,0-5 (11,9,8,9,9) on day8 | 10.7 µU/mL | Standard Deviation 5.6 |
| Empagliflozin 10 mg qd | Serum Insulin | Emax,0-5 (12,9,9,9,9) on day-2 | 51.2 µU/mL | Standard Deviation 23.4 |
| Empagliflozin 10 mg qd | Serum Insulin | Emax,0-12 (12,9,9,9,9) on day-2 | 72.1 µU/mL | Standard Deviation 27.7 |
| Empagliflozin 10 mg qd | Serum Insulin | Emin,0-12 (12,9,9,9,9) on day-2 | 13.5 µU/mL | Standard Deviation 4.37 |
| Empagliflozin 10 mg qd | Serum Insulin | Emax,0-5 (11,9,8,9,9) on day8 | 56.3 µU/mL | Standard Deviation 25.4 |
| Empagliflozin 10 mg qd | Serum Insulin | Emin,0-5 (12,9,9,9,9) on day-2 | 13.7 µU/mL | Standard Deviation 4.62 |
| Empagliflozin 10 mg qd | Serum Insulin | Emax,0-12 (11,9,8,9,9) on day8 | 68.6 µU/mL | Standard Deviation 31.1 |
| Empagliflozin 10 mg qd | Serum Insulin | Emin,0-12 (11,9,8,9,9) on day8 | 10.7 µU/mL | Standard Deviation 5.6 |
| Empagliflozin 25 mg qd | Serum Insulin | Emin,0-5 (12,9,9,9,9) on day-2 | 9.16 µU/mL | Standard Deviation 7.59 |
| Empagliflozin 25 mg qd | Serum Insulin | Emax,0-5 (12,9,9,9,9) on day-2 | 40.2 µU/mL | Standard Deviation 19.4 |
| Empagliflozin 25 mg qd | Serum Insulin | Emin,0-12 (11,9,8,9,9) on day8 | 5.17 µU/mL | Standard Deviation 3.19 |
| Empagliflozin 25 mg qd | Serum Insulin | Emax,0-12 (12,9,9,9,9) on day-2 | 48.7 µU/mL | Standard Deviation 30.9 |
| Empagliflozin 25 mg qd | Serum Insulin | Emax,0-5 (11,9,8,9,9) on day8 | 36.2 µU/mL | Standard Deviation 37.3 |
| Empagliflozin 25 mg qd | Serum Insulin | Emin,0-5 (11,9,8,9,9) on day8 | 5.33 µU/mL | Standard Deviation 3.14 |
| Empagliflozin 25 mg qd | Serum Insulin | Emax,0-12 (11,9,8,9,9) on day8 | 44.4 µU/mL | Standard Deviation 35.5 |
| Empagliflozin 25 mg qd | Serum Insulin | Emin,0-12 (12,9,9,9,9) on day-2 | 9.16 µU/mL | Standard Deviation 7.59 |
| Empagliflozin 100 mg qd | Serum Insulin | Emin,0-12 (11,9,8,9,9) on day8 | 3.96 µU/mL | Standard Deviation 2.79 |
| Empagliflozin 100 mg qd | Serum Insulin | Emin,0-12 (12,9,9,9,9) on day-2 | 7.86 µU/mL | Standard Deviation 2.18 |
| Empagliflozin 100 mg qd | Serum Insulin | Emax,0-12 (11,9,8,9,9) on day8 | 37.3 µU/mL | Standard Deviation 8.1 |
| Empagliflozin 100 mg qd | Serum Insulin | Emin,0-5 (11,9,8,9,9) on day8 | 3.96 µU/mL | Standard Deviation 2.79 |
| Empagliflozin 100 mg qd | Serum Insulin | Emax,0-5 (12,9,9,9,9) on day-2 | 35.2 µU/mL | Standard Deviation 15.5 |
| Empagliflozin 100 mg qd | Serum Insulin | Emax,0-12 (12,9,9,9,9) on day-2 | 45.3 µU/mL | Standard Deviation 11.3 |
| Empagliflozin 100 mg qd | Serum Insulin | Emin,0-5 (12,9,9,9,9) on day-2 | 7.86 µU/mL | Standard Deviation 2.18 |
| Empagliflozin 100 mg qd | Serum Insulin | Emax,0-5 (11,9,8,9,9) on day8 | 29.6 µU/mL | Standard Deviation 11.7 |
Secondary
Serum Insulin
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.
Time frame: 0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8
Population: PDS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Insulin | AUEC0-5 (12,9,9,9,9) on day-2 | 134 µU*h/mL | Standard Deviation 52.5 |
| Placebo | Serum Insulin | AUEC0-5 (11,9,8,9,9) on day8 | 122 µU*h/mL | Standard Deviation 52 |
| Placebo | Serum Insulin | AUEC0-12 (11,9,7,9,8) on day8 | 288 µU*h/mL | Standard Deviation 97.1 |
| Placebo | Serum Insulin | AUEC0-12 (12,9,9,9,9) on day-2 | 300 µU*h/mL | Standard Deviation 111 |
| Empagliflozin 2.5 mg qd | Serum Insulin | AUEC0-12 (11,9,7,9,8) on day8 | 417 µU*h/mL | Standard Deviation 132 |
| Empagliflozin 2.5 mg qd | Serum Insulin | AUEC0-5 (12,9,9,9,9) on day-2 | 185 µU*h/mL | Standard Deviation 79.2 |
| Empagliflozin 2.5 mg qd | Serum Insulin | AUEC0-12 (12,9,9,9,9) on day-2 | 474 µU*h/mL | Standard Deviation 149 |
| Empagliflozin 2.5 mg qd | Serum Insulin | AUEC0-5 (11,9,8,9,9) on day8 | 174 µU*h/mL | Standard Deviation 80.9 |
| Empagliflozin 10 mg qd | Serum Insulin | AUEC0-5 (12,9,9,9,9) on day-2 | 175 µU*h/mL | Standard Deviation 70.7 |
| Empagliflozin 10 mg qd | Serum Insulin | AUEC0-12 (12,9,9,9,9) on day-2 | 471 µU*h/mL | Standard Deviation 143 |
| Empagliflozin 10 mg qd | Serum Insulin | AUEC0-5 (11,9,8,9,9) on day8 | 180 µU*h/mL | Standard Deviation 74.7 |
| Empagliflozin 10 mg qd | Serum Insulin | AUEC0-12 (11,9,7,9,8) on day8 | 387 µU*h/mL | Standard Deviation 154 |
| Empagliflozin 25 mg qd | Serum Insulin | AUEC0-12 (12,9,9,9,9) on day-2 | 336 µU*h/mL | Standard Deviation 161 |
| Empagliflozin 25 mg qd | Serum Insulin | AUEC0-5 (11,9,8,9,9) on day8 | 117 µU*h/mL | Standard Deviation 103 |
| Empagliflozin 25 mg qd | Serum Insulin | AUEC0-5 (12,9,9,9,9) on day-2 | 137 µU*h/mL | Standard Deviation 64.7 |
| Empagliflozin 25 mg qd | Serum Insulin | AUEC0-12 (11,9,7,9,8) on day8 | 266 µU*h/mL | Standard Deviation 193 |
| Empagliflozin 100 mg qd | Serum Insulin | AUEC0-12 (12,9,9,9,9) on day-2 | 282 µU*h/mL | Standard Deviation 41.6 |
| Empagliflozin 100 mg qd | Serum Insulin | AUEC0-12 (11,9,7,9,8) on day8 | 275 µU*h/mL | Standard Deviation 72.4 |
| Empagliflozin 100 mg qd | Serum Insulin | AUEC0-5 (11,9,8,9,9) on day8 | 101 µU*h/mL | Standard Deviation 37.2 |
| Empagliflozin 100 mg qd | Serum Insulin | AUEC0-5 (12,9,9,9,9) on day-2 | 119 µU*h/mL | Standard Deviation 35.9 |
Secondary
Terminal Rate Constant in Plasma
Terminal rate constant in plasma after first dose and at steady-state
Time frame: -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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Terminal Rate Constant in Plasma | Terminal rate after first dose | 0.0618 1/h | Geometric Coefficient of Variation 22.4 |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Terminal Rate Constant in Plasma | Terminal rate at steady-state (N=9,8,9,8) | 0.0491 1/h | Geometric Coefficient of Variation 17.5 |
| Empagliflozin 2.5 mg qd | Terminal Rate Constant in Plasma | Terminal rate after first dose | 0.0586 1/h | Geometric Coefficient of Variation 11.5 |
| Empagliflozin 10 mg qd | Terminal Rate Constant in Plasma | Terminal rate after first dose | 0.0654 1/h | Geometric Coefficient of Variation 19.9 |
| Empagliflozin 10 mg qd | Terminal Rate Constant in Plasma | Terminal rate at steady-state (N=9,8,9,8) | 0.0658 1/h | Geometric Coefficient of Variation 18.8 |
| Empagliflozin 25 mg qd | Terminal Rate Constant in Plasma | Terminal rate after first dose | 0.0527 1/h | Geometric Coefficient of Variation 26.8 |
| Empagliflozin 25 mg qd | Terminal Rate Constant in Plasma | Terminal rate at steady-state (N=9,8,9,8) | 0.0409 1/h | Geometric Coefficient of Variation 48.4 |
Secondary
Time to Maximum Concentration of the Analyte in Plasma
Time from last dosing to maximum concentration of the analyte in plasma (tmax) after first dose and at steady-state
Time frame: -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
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time to Maximum Concentration of the Analyte in Plasma | tmax after first dose | 1.50 h | Full Range 27.5 |
| Placebo | 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 |
| Empagliflozin 2.5 mg qd | Time to Maximum Concentration of the Analyte in Plasma | tmax at steady-state (N=9,8,9,8) | 1.50 h | Full Range 24.3 |
| Empagliflozin 2.5 mg qd | Time to Maximum Concentration of the Analyte in Plasma | tmax after first dose | 1.50 h | Full Range 18.2 |
| Empagliflozin 10 mg qd | Time to Maximum Concentration of the Analyte in Plasma | tmax after first dose | 1.50 h | Full Range 38.5 |
| Empagliflozin 10 mg qd | Time to Maximum Concentration of the Analyte in Plasma | tmax at steady-state (N=9,8,9,8) | 2.00 h | Full Range 62.6 |
| Empagliflozin 25 mg qd | Time to Maximum Concentration of the Analyte in Plasma | tmax after first dose | 3.00 h | Full Range 77.8 |
| Empagliflozin 25 mg qd | Time to Maximum Concentration of the Analyte in Plasma | tmax at steady-state (N=9,8,9,8) | 1.50 h | Full Range 62.3 |