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

NCT01316341 | Completed Phase 1 Results

• 1 other identifier: 1245.44
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (28)

• Maximum Measured Concentration (Cmax)

  Maximum measured concentration of the analyte in plasma after the first dose on day 1.

  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 to Maximum Measured Concentration (Tmax)

  Time from dosing to the maximum measured concentration of the analyte in plasma, after the first dose on day 1.

  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 Curve 0 to Infinity (AUC0-∞) After Single Dosing

  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

  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 Curve 0 to the Last Quantifiable Data Point (AUC0-tz)

  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.

  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 (λz)

  Terminal Rate Constant in Plasma (λz), after the first dose on day 1

  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 (t1/2)

  Terminal half-life of empagliflozin (empa) in plasma after the first dose on day 1

  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 (MRTpo)

  Mean residence time of empagliflozin (empa) in the body after the first dose on day 1.

  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 After Extravascular Administration (CL/F)

  Apparent clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

  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 (Vz/F)

  Apparent volume of distribution during the terminal phase λz, after the first dose on day 1.

  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

• Amount of Empagliflozin Eliminated in Urine in the Time Interval 0 Hours to 24 Hours (Ae 0-24)

  Amount of empagliflozin (empa) eliminated in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

  Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

• Fraction of Empagliflozin Excreted Unchanged in Urine in the Time Interval 0 Hours to 24 Hours (fe 0-24).

  Fraction of empagliflozin (empa) excreted unchanged in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

  Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

• Renal Clearance After Extravascular Administration (CL R,0-48)

  Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

  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 Over a Uniform Dosing Interval (Cmax,ss)

  Maximum measured concentration of empagliflozin (empa) in plasma at steady state over a uniform dosing interval.

  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 Over a Uniform Dosing Interval at Steady State (Tmax,ss)

  Time from last dosing to maximum measured concentration of empagliflozin (empa) in plasma over a uniform dosing interval 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

• Area Under the Concentration-time Curve in Plasma at Steady State Over a Uniform Dosing Interval (AUCτ,ss)

  Area under the concentration-time curve of empagliflozin (empa) in plasma at steady state over a uniform dosing interval, 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

• Terminal Rate Constant in Plasma at Steady State (λz,ss)

  Terminal rate constant 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

• Terminal Half-life in Plasma at Steady State (t1/2,ss)

  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

• Mean Residence Time at Steady State (MRTpo,ss)

  Mean residence time of empagliflozin (empa) in the body at steady state after multiple oral administrations

  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 After Extravascular Administration (CL/Fss)

  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

• Apparent Volume of Distribution During the Terminal Phase λz (Vz/Fss)

  Apparent volume of distribution during the terminal phase λz at steady state following oral 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

• Amount of Analyte Eliminated in Urine at Steady State in Time Interval 0 Hours to 24 Hours (Ae 0-24,ss)

  Amount of empagliflozin (empa) eliminated 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

• Fraction of Empagliflozin Excreted Unchanged in Urine at Steady State in the Time Interval 0 Hours to 24 Hours (fe 0-24,ss)

  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)

  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

• Accumulation Ratio Based on AUC (R A,AUC)

  Accumulation ratio of empagliflozin (empa) based on AUC, 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, and16h after drug administration on days 1 and 9

• Accumulation Ratio Based on Cmax (R A,Cmax)

  Accumulation ratio of empagliflozin (empa) based on Cmax, 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, and16h after drug administration between days 5 and 9

• Predose Plasma Concentration Before Planned Dose x (Cpre,x)

  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

• Urinary Glucose Excretion (UGE) Change From Baseline

  Change from day -1 in urinary glucose excretion in a 24 hour collection period per time point.

  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

  Fasting Plasma Glucose (FPG) change from baseline between day 1 and day 9.

  Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Secondary Outcomes (1)

• 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

Study Arms (3)

BI10773 low dose Per Os(p.o.)

EXPERIMENTAL

patient to receive a tablet containing low dose BI10773 Per Os(p.o.) plus one placebo

Drug: Placebo; Drug: BI10773

Placebo

PLACEBO COMPARATOR

patient to receive two placebos

Drug: Placebo

BI10773 high dose Per Os(p.o.)

EXPERIMENTAL

patient to receive a tablet containing high dose BI10773 Per Os(p.o.) plus one placebo

Drug: BI10773; Drug: Placebo

Interventions

BI10773 DRUG

patient to receive a tablet containing high dose BI10773 p.o. plus one placebo

BI10773 high dose Per Os(p.o.)

Placebo DRUG

patient to receive two placebos

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1245.44.86001 Boehringer Ingelheim Investigational Site

Beijing, China

Location

Related Publications (1)

• Zhao X, Cui Y, Zhao S, Lang B, Broedl UC, Salsali A, Pinnetti S, Macha S. Pharmacokinetic and Pharmacodynamic Properties and Tolerability of Single- and multiple-dose Once-daily Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, in Chinese Patients With Type 2 Diabetes Mellitus. Clin Ther. 2015 Jul 1;37(7):1493-502. doi: 10.1016/j.clinthera.2015.05.001. Epub 2015 Jun 19.

  PMID: 26101175 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 16, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2012
• Last Updated: June 17, 2014
• Results First Posted: June 17, 2014

Record last verified: 2014-05

Locations

CN (1)