- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01316341
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Empagliflozin in Chinese Female and Male Patients With Type 2 Diabetes Mellitus
Pharmacokinetics and Pharmacodynamics of BI 10773 After Single and Multiple Oral Dose of 10 mg and 25 mg BI 10773 in Chinese Male and Female Type 2 Diabetic Patients
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Beijing, China
- 1245.44.86001 Boehringer Ingelheim Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Chinese male and 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 thiazolidinediones with at least one agent taken at 50% of its maximum dose or less, unchanged for at least 12 weeks before randomization
- Glycosylated haemoglobin A1(HbA1c)<=8.5% and >=7.0% at screening,age>=21 and age<=70 years (male and female patients),BMI>=19 and <=40 kg/m2
- Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation.
Exclusion criteria:
- Patient who did not discontinue the antidiabetic treatment with insulin or glitazones, DPP-IV at least before 12 weeks before randomization
- Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast at screening visit
- Clinically relevant concomitant diseases other than type 2 diabetes, hyperlipidaemia and medically treated hypertension, such as:
4 Any late stage complication of diabetes (e.g. retinopathy, polyneuropathy, vegetative disorders, diabetic foot) 5 Renal insufficiency (calculated creatinine clearance < 80 ml/min/1.73m²) 6 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 7 Neurological disorders (such as epilepsy) or psychiatric disorders 8 Acute or relevant chronic infections (e.g. HIV, repeated urogenital infections) 9 Any gastrointestinal, hepatic, respiratory, endocrine or immunological disorder 10. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 11. A marked baseline prolongation of QT/QTc interval (e.g., ECG demonstration of a QTc interval >450 ms ) at screening visit
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BI10773 low dose Per Os(p.o.)
patient to receive a tablet containing low dose BI10773 Per Os(p.o.) plus one placebo
|
patient to receive a tablet containing high dose BI10773 p.o. plus one placebo
patient to receive two placebos
patient to receive a tablet containing low dose BI10773 p.o. plus one placebo
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Placebo Comparator: Placebo
patient to receive two placebos
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patient to receive two placebos
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Experimental: BI10773 high dose Per Os(p.o.)
patient to receive a tablet containing high dose BI10773 Per Os(p.o.) plus one placebo
|
patient to receive a tablet containing high dose BI10773 p.o. plus one placebo
patient to receive two placebos
patient to receive a tablet containing low dose BI10773 p.o. plus one placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Measured Concentration (Cmax)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
|
Maximum measured concentration of the analyte in plasma after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Time to Maximum Measured Concentration (Tmax)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
|
Time from dosing to the maximum measured concentration of the analyte in plasma, after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Area Under the Curve 0 to Infinity (AUC0-∞) After Single Dosing
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity, after the first dose on day 1
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point, after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Terminal Rate Constant (λz)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Terminal Rate Constant in Plasma (λz), after the first dose on day 1
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Terminal Half-life (t1/2)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Terminal half-life of empagliflozin (empa) in plasma after the first dose on day 1
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Mean Residence Time (MRTpo)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Mean residence time of empagliflozin (empa) in the body after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Apparent Clearance of Empagliflozin After Extravascular Administration (CL/F)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Apparent clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Apparent Volume of Distribution During the Terminal Phase λz (Vz/F)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Apparent volume of distribution during the terminal phase λz, after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Amount of Empagliflozin Eliminated in Urine in the Time Interval 0 Hours to 24 Hours (Ae 0-24)
Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Amount of empagliflozin (empa) eliminated in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.
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Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Fraction of Empagliflozin Excreted Unchanged in Urine in the Time Interval 0 Hours to 24 Hours (fe 0-24).
Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Fraction of empagliflozin (empa) excreted unchanged in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.
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Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Renal Clearance After Extravascular Administration (CL R,0-48)
Time Frame: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.
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5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration
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Maximum Measured Concentration Over a Uniform Dosing Interval (Cmax,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Maximum measured concentration of empagliflozin (empa) in plasma at steady state over a uniform dosing interval.
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Time From Last Dosing to Maximum Measured Concentration Over a Uniform Dosing Interval at Steady State (Tmax,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Time from last dosing to maximum measured concentration of empagliflozin (empa) in plasma over a uniform dosing interval at steady state, after multiple dosing.
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Area Under the Concentration-time Curve in Plasma at Steady State Over a Uniform Dosing Interval (AUCτ,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Area under the concentration-time curve of empagliflozin (empa) in plasma at steady state over a uniform dosing interval, after multiple dosing
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Terminal Rate Constant in Plasma at Steady State (λz,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Terminal rate constant in plasma at steady state, after multiple dosing.
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Terminal Half-life in Plasma at Steady State (t1/2,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Terminal half-life of empagliflozin (empa) in plasma at steady state, after multiple dosing.
|
5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Mean Residence Time at Steady State (MRTpo,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Mean residence time of empagliflozin (empa) in the body at steady state after multiple oral administrations
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Apparent Clearance of Empagliflozin After Extravascular Administration (CL/Fss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Apparent clearance of empagliflozin (empa) in the plasma at steady state following multiple oral dose administration.
|
5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Apparent Volume of Distribution During the Terminal Phase λz (Vz/Fss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Apparent volume of distribution during the terminal phase λz at steady state following oral administration after multiple dosing
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
|
Amount of Analyte Eliminated in Urine at Steady State in Time Interval 0 Hours to 24 Hours (Ae 0-24,ss)
Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Amount of empagliflozin (empa) eliminated in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.
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Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Fraction of Empagliflozin Excreted Unchanged in Urine at Steady State in the Time Interval 0 Hours to 24 Hours (fe 0-24,ss)
Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
|
Fraction of empagliflozin (empa) excreted unchanged in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.
|
Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
|
Renal Clearance at Steady State (CL R,ss)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
|
Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after multiple dosing.
|
5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9
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Accumulation Ratio Based on AUC (R A,AUC)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration on days 1 and 9
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Accumulation ratio of empagliflozin (empa) based on AUC, after multiple dosing
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration on days 1 and 9
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Accumulation Ratio Based on Cmax (R A,Cmax)
Time Frame: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration between days 5 and 9
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Accumulation ratio of empagliflozin (empa) based on Cmax, after multiple dosing
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5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration between days 5 and 9
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Predose Plasma Concentration Before Planned Dose x (Cpre,x)
Time Frame: 5 minutes before drug administration
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Predose plasma concentration of empagliflozin (empa) before planned dose by day. This endpoint in steady state is identical to Cmin,ss. |
5 minutes before drug administration
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Urinary Glucose Excretion (UGE) Change From Baseline
Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
|
Change from day -1 in urinary glucose excretion in a 24 hour collection period per time point.
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Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Fasting Plasma Glucose (FPG) Change From Baseline
Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
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Fasting Plasma Glucose (FPG) change from baseline between day 1 and day 9.
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Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Relevant Abnormalities for Protocol-Specified Significant Adverse Events, Hypoglycaemic Events, Vital Signs, Blood Chemistry, Rescue Therapy, Body Weight and Waist Circumference
Time Frame: Drug administration until end of trial, up to 21 days
|
Clinically relevant abnormalities for protocol-specified significant adverse events, hypoglycaemic events, vital signs, blood chemistry, use of rescue therapy, change in body weight and change in waist circumference. Results shown are for hypoglycaemic events, as this was the only event that occurred for this endpoint. |
Drug administration until end of trial, up to 21 days
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1245.44
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