Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Empagliflozin in Chinese Female and Male Patients With Type 2 Diabetes Mellitus

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Placebo; Drug: BI10773

• Registration Number: NCT01316341
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

the pharmacokinetics, pharmacodynamics and safety and tolerability of single and multiple oral doses of BI 10773 at low dose once daily (q.d.) and high dose q.d. administered to Chinese female and male patients with type 2 diabetes will be investigated.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-03-15
• Study First Submitted QC: 2011-03-15
• Study First Posted: 2011-03-16
• Primary Completion: 2012-01
• Status Verified: 2014-05
• Results First Submitted: 2014-05-16
• Results First Submitted QC: 2014-05-16
• Last Update Submitted: 2014-05-16
• Results First Posted: 2014-06-17
• Last Update Posted: 2014-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BI10773 low dose Per Os(p.o.)	BI10773	patient to receive a tablet containing low dose BI10773 Per Os(p.o.) plus one placebo
BI10773 low dose Per Os(p.o.)	Placebo	patient to receive a tablet containing low dose BI10773 Per Os(p.o.) plus one placebo
Placebo	Placebo	patient to receive two placebos
BI10773 high dose Per Os(p.o.)	BI10773	patient to receive a tablet containing high dose BI10773 Per Os(p.o.) plus one placebo
BI10773 high dose Per Os(p.o.)	Placebo	patient to receive a tablet containing high dose BI10773 Per Os(p.o.) plus one placebo

Primary Outcome Measures

Name	Time	Method
Apparent Clearance of Empagliflozin After Extravascular Administration (CL/F)	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	Apparent clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.
Renal Clearance After Extravascular Administration (CL R,0-48)	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	Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.
Terminal Half-life (t1/2)	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	Terminal half-life of empagliflozin (empa) in plasma after the first dose on day 1
Mean Residence Time (MRTpo)	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	Mean residence time of empagliflozin (empa) in the body after the first dose on day 1.
Amount of Empagliflozin Eliminated in Urine in the Time Interval 0 Hours to 24 Hours (Ae 0-24)	Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration	Amount of empagliflozin (empa) eliminated in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.
Time From Last Dosing to Maximum Measured Concentration Over a Uniform Dosing Interval at Steady State (Tmax,ss)	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	Time from last dosing to maximum measured concentration of empagliflozin (empa) in plasma over a uniform dosing interval at steady state, after multiple dosing.
Terminal Rate Constant in Plasma at Steady State (λz,ss)	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	Terminal rate constant in plasma at steady state, after multiple dosing.
Apparent Volume of Distribution During the Terminal Phase λz (Vz/Fss)	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	Apparent volume of distribution during the terminal phase λz at steady state following oral administration after multiple dosing
Area Under the Curve 0 to Infinity (AUC0-∞) After Single Dosing	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	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
Terminal Rate Constant (λz)	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	Terminal Rate Constant in Plasma (λz), after the first dose on day 1
Apparent Volume of Distribution During the Terminal Phase λz (Vz/F)	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	Apparent volume of distribution during the terminal phase λz, after the first dose on day 1.
Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)	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	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.
Area Under the Concentration-time Curve in Plasma at Steady State Over a Uniform Dosing Interval (AUCτ,ss)	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	Area under the concentration-time curve of empagliflozin (empa) in plasma at steady state over a uniform dosing interval, after multiple dosing
Mean Residence Time at Steady State (MRTpo,ss)	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	Mean residence time of empagliflozin (empa) in the body at steady state after multiple oral administrations
Amount of Analyte Eliminated in Urine at Steady State in Time Interval 0 Hours to 24 Hours (Ae 0-24,ss)	Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration	Amount of empagliflozin (empa) eliminated in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.
Maximum Measured Concentration (Cmax)	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.
Time to Maximum Measured Concentration (Tmax)	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.
Fraction of Empagliflozin Excreted Unchanged in Urine in the Time Interval 0 Hours to 24 Hours (fe 0-24).	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 in the time interval 0 hours to 24 hours, after the first dose on day 1.
Maximum Measured Concentration Over a Uniform Dosing Interval (Cmax,ss)	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	Maximum measured concentration of empagliflozin (empa) in plasma at steady state over a uniform dosing interval.
Terminal Half-life in Plasma at Steady State (t1/2,ss)	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	Terminal half-life of empagliflozin (empa) in plasma at steady state, after multiple dosing.
Apparent Clearance of Empagliflozin After Extravascular Administration (CL/Fss)	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	Apparent clearance of empagliflozin (empa) in the plasma at steady state following multiple oral dose administration.
Fraction of Empagliflozin Excreted Unchanged in Urine at Steady State in the Time Interval 0 Hours to 24 Hours (fe 0-24,ss)	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.
Renal Clearance at Steady State (CL R,ss)	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.
Accumulation Ratio Based on Cmax (R A,Cmax)	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	Accumulation ratio of empagliflozin (empa) based on Cmax, after multiple dosing
Predose Plasma Concentration Before Planned Dose x (Cpre,x)	5 minutes before drug administration	Predose plasma concentration of empagliflozin (empa) before planned dose by day.; This endpoint in steady state is identical to Cmin,ss.
Accumulation Ratio Based on AUC (R A,AUC)	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	Accumulation ratio of empagliflozin (empa) based on AUC, after multiple dosing
Urinary Glucose Excretion (UGE) Change From Baseline	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.
Fasting Plasma Glucose (FPG) Change From Baseline	Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration	Fasting Plasma Glucose (FPG) change from baseline between day 1 and day 9.

Secondary Outcome Measures

Name	Time	Method
Clinical Relevant Abnormalities for Protocol-Specified Significant Adverse Events, Hypoglycaemic Events, Vital Signs, Blood Chemistry, Rescue Therapy, Body Weight and Waist Circumference	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.

Trial Locations

Locations (1)

1245.44.86001 Boehringer Ingelheim Investigational Site; 🇨🇳 Beijing, China