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Phase 1 Completed N=24 Randomized Double-blind Treatment

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

Source: ClinicalTrials.gov NCT01316341 ↗
Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Jun 2014
Primary outcomePrimary: Maximum Measured Concentration (Cmax) — 436; 1090 nmol/L

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Maximum Measured Concentration (Cmax)
436; 1090
PRIMARY
Time to Maximum Measured Concentration (Tmax)
1.13; 1.50
PRIMARY
Area Under the Curve 0 to Infinity (AUC0-∞) After Single Dosing
2560; 7250
PRIMARY
Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
2510; 7070
PRIMARY
Terminal Rate Constant (λz)
0.0749; 0.0664
PRIMARY
Terminal Half-life (t1/2)
9.25; 10.4
PRIMARY
Mean Residence Time (MRTpo)
9.29; 10.2
PRIMARY
Apparent Clearance of Empagliflozin After Extravascular Administration (CL/F)
144; 127
PRIMARY
Apparent Volume of Distribution During the Terminal Phase λz (Vz/F)
115; 115
PRIMARY
Amount of Empagliflozin Eliminated in Urine in the Time Interval 0 Hours to 24 Hours (Ae 0-24)
4030; 9940
PRIMARY
Fraction of Empagliflozin Excreted Unchanged in Urine in the Time Interval 0 Hours to 24 Hours (fe 0-24).
18.2; 17.9
PRIMARY
Renal Clearance After Extravascular Administration (CL R,0-48)
28.9; 25.6
PRIMARY
Maximum Measured Concentration Over a Uniform Dosing Interval (Cmax,ss)
489; 1250
PRIMARY
Time From Last Dosing to Maximum Measured Concentration Over a Uniform Dosing Interval at Steady State (Tmax,ss)
1.17; 1.37
PRIMARY
Area Under the Concentration-time Curve in Plasma at Steady State Over a Uniform Dosing Interval (AUCτ,ss)
2650; 7520
PRIMARY
Terminal Rate Constant in Plasma at Steady State (λz,ss)
0.0559; 0.0588
PRIMARY
Terminal Half-life in Plasma at Steady State (t1/2,ss)
12.4; 11.8
PRIMARY
Mean Residence Time at Steady State (MRTpo,ss)
10.5; 10.2
PRIMARY
Apparent Clearance of Empagliflozin After Extravascular Administration (CL/Fss)
139; 123
PRIMARY
Apparent Volume of Distribution During the Terminal Phase λz (Vz/Fss)
150; 125
PRIMARY
Amount of Analyte Eliminated in Urine at Steady State in Time Interval 0 Hours to 24 Hours (Ae 0-24,ss)
4420; 11600
PRIMARY
Fraction of Empagliflozin Excreted Unchanged in Urine at Steady State in the Time Interval 0 Hours to 24 Hours (fe 0-24,ss)
19.9; 20.9
PRIMARY
Renal Clearance at Steady State (CL R,ss)
27.8; 26.1
PRIMARY
Accumulation Ratio Based on AUC (R A,AUC)
1.14; 1.17
PRIMARY
Accumulation Ratio Based on Cmax (R A,Cmax)
1.12; 1.15
PRIMARY
Predose Plasma Concentration Before Planned Dose x (Cpre,x)
24.64; 70.54; 25.70; 80.27; 25.24; 78.96
PRIMARY
Urinary Glucose Excretion (UGE) Change From Baseline
-988.38; 87680.85; 82791.86; -4106.10; 95765.72; 82633.88
PRIMARY
Fasting Plasma Glucose (FPG) Change From Baseline
-3.67; -25.56; -31.44
SECONDARY
Clinical Relevant Abnormalities for Protocol-Specified Significant Adverse Events, Hypoglycaemic Events, Vital Signs, Blood Chemistry, Rescue Therapy, Body Weight and Waist Circumference
0; 1; 0

Eligibility Criteria

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) =7.0% at screening, age>=21 and age =19 and 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 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01316341). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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