Safety, Tolerability, Pharmacokinetics and Pharmacodynami... | NCT01924767

ID	Type	Description	Link
2007-000654-32	EudraCT Number	EudraCT

Status Module

Label	Type	Description	Intervention Names
BI 10773 (dose group 3)	Experimental	multiple doses as tablet	Drug: BI 10773 Placebo Drug: BI 10773
BI 10773 (dose group 4)	Experimental	multiple doses as tablet	Drug: BI 10773 Drug: BI 10773 Placebo
BI 10773 (dose group 1)	Experimental	multiple doses as tablet	Drug: BI 10773 Placebo Drug: BI 10773
BI 10773 (dose group 2)	Experimental	multiple doses as tablet	Drug: BI 10773 Placebo Drug: BI 10773

Name	Type	Description	Arm Group Labels	Other Names
BI 10773 Placebo	Drug	po taken fasting with 240 mL water	BI 10773 (dose group 2)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).	day 1 to day 21
Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results	Percentage of participants with clinically relevant findings in electrocardiogram (ECG) results	day 1 to day 21
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.	Baseline and Day 9
Assessment of Tolerability by Investigator	Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad.	day 21

Secondary Outcomes

Measure	Description	Time Frame
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)	-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.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

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.
Glycosylated haemoglobin A1 (HbA1c) £ 8.5 % at screening.
Age >21 and Age <70 years (male and hysterectomised female patients) Age >60 and Age <70 years (postmenopausal female patients)
Body Mass Index (BMI) >18.5 and <40 kg/m2
Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion criteria:

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)
Fasted blood glucose > 240 mg/dl (>13.3 mmol/L) on two consecutive days during washout.
Glycosylated haemoglobin A1 (HbA1c) >8.5% at screening
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
History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
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)

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Patients were treated with matching placebo as tablet once daily (qd) in the morning.
FG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
BG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily in the morning.
BG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily in the morning.
BG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily in the morning.
BG004	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily in the morning.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG00012 BG0019 BG0029 BG0039 BG0049 BG00548

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

Treated set.

Posted

Number

percentage of participants

day 1 to day 21

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG004	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.

Units	Counts
Participants	OG00012 OG0019 OG0029 OG003

Title

Denominators

Categories

Cardiac disorders

Title	Measurements
	OG0000.0 OG0010.0 OG0020.0 OG003

Primary

Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results

Percentage of participants with clinically relevant findings in electrocardiogram (ECG) results

Treated set

Posted

Number

percentage of participants

day 1 to day 21

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG004	Empagliflozin 100 mg qd

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.

Treated set

Posted

Mean

Standard Deviation

frequency of micturition

Baseline and Day 9

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG004	Empagliflozin 100 mg qd

Primary

Assessment of Tolerability by Investigator

Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory and bad.

Treated set

Posted

Number

percentage of participants

day 21

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG004	Empagliflozin 100 mg qd

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)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol/L

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

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.

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol*h/L

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

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

PK set

Posted

Median

Full Range

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.

Secondary

Terminal Rate Constant in Plasma

Terminal rate constant in plasma after first dose and at steady-state

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

1/h

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.

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.

PK Set

Posted

Geometric Mean

Geometric Coefficient of Variation

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd

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).

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd

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)

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

nmol

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

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.

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.

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

percent of analyte

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

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

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.

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

mL/min

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

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

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

PTF(%) of Empagliflozin

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.

Secondary

Linearity Index

The linearity index is defined as AUC0-tau divided by AUC0-∞ both at steady state.

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

Fraction

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily (qd) in the morning.

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

PK set

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

-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.

ID	Title	Description
OG000	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG001	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 100 mg qd

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.

Pharmacodynamic (PD) analysis set (PDS) contains of all patients who received study medication and have evaluable pharmacodynamic parameter data.

Posted

Mean

Standard Deviation

-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

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

Secondary

Mean Daily Glucose

Change from baseline to Day 8 in mean daily glucose. Baseline is defined as Day -2.

PDS

Posted

Mean

Standard Deviation

mg/dL

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

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG004

Secondary

Fasting Plasma Glucose

Percentage change from baseline to Day 8 in fasting plasma glucose. Baseline is defined as Day -2.

PDS

Posted

Mean

Standard Deviation

percentage of fasting plasma glucose

-0:30 (Pre dose samples)

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.
OG004	Empagliflozin 100 mg qd

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.

PDS

Posted

Mean

Standard Deviation

µU*h/mL

0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily (qd) in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

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)

PDS

Posted

Mean

Standard Deviation

µU/mL

0.0h, 2h, 5h, 7h, 10h, 12h on day -2 & day 8

ID	Title	Description
OG000	Placebo	Patients were treated with matching placebo as tablet once daily (qd) in the morning.
OG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily (qd) in the morning.
OG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily (qd) in the morning.
OG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily (qd) in the morning.

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Patients were treated with matching placebo as tablet once daily in the morning.	12	5	12
EG001	Empagliflozin 2.5 mg qd	Patients were treated with 2.5 mg Empagliflozin as tablet once daily in the morning.	9	6	9
EG002	Empagliflozin 10 mg qd	Patients were treated with 10 mg Empagliflozin as tablet once daily in the morning.	9	5	9
EG003	Empagliflozin 25 mg qd	Patients were treated with 25 mg Empagliflozin as tablet once daily in the morning.	9	5	9
EG004	Empagliflozin 100 mg qd	Patients were treated with 100 mg Empagliflozin as tablet once daily in the morning.	9	3	9

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cellulitis	Infections and infestations	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG0030 affected9 at risk EG0040 affected9 at risk
Nasopharyngitis	Infections and infestations	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Rhinitis	Infections and infestations	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0022 affected9 at risk EG003
Headache	Nervous system disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Paraesthesia	Nervous system disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0012 affected9 at risk EG0020 affected9 at risk EG003
Dizziness	Nervous system disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0011 affected9 at risk EG0021 affected9 at risk EG003
Sciatica	Nervous system disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0011 affected9 at risk EG0021 affected9 at risk EG003
Eye pruritus	Eye disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Circulatory collapse	Vascular disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Thrombophlebitis	Vascular disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0012 affected9 at risk EG0020 affected9 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Constipation	Gastrointestinal disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Gastric disorder	Gastrointestinal disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0011 affected9 at risk EG0020 affected9 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0021 affected9 at risk EG003
Injection site thrombosis	General disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Oedema peripheral	General disorders	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Hepatic enzyme increased	Investigations	MEDDRA 10.1	Systematic Assessment	EG0001 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003
Arthropod sting	Injury, poisoning and procedural complications	MEDDRA 10.1	Systematic Assessment	EG0000 affected12 at risk EG0010 affected9 at risk EG0020 affected9 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases