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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01316341
First received: March 15, 2011
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: BI10773
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Maximum measured concentration of the analyte in plasma after the first dose on day 1.

  • 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 ] [ Designated as safety issue: No ]
    Time from dosing to the maximum measured concentration of the analyte in plasma, after the first dose on day 1.

  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Terminal Rate Constant in Plasma (λz), after the first dose on day 1

  • 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 ] [ Designated as safety issue: No ]
    Terminal half-life of empagliflozin (empa) in plasma after the first dose on day 1

  • 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 ] [ Designated as safety issue: No ]
    Mean residence time of empagliflozin (empa) in the body after the first dose on day 1.

  • 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 ] [ Designated as safety issue: No ]
    Apparent clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

  • 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 ] [ Designated as safety issue: No ]
    Apparent volume of distribution during the terminal phase λz, 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) [ Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration ] [ Designated as safety issue: No ]
    Amount of empagliflozin (empa) eliminated in urine in the time interval 0 hours to 24 hours, 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). [ Time Frame: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration ] [ Designated as safety issue: No ]
    Fraction of empagliflozin (empa) excreted unchanged in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

  • 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 ] [ Designated as safety issue: No ]
    Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

  • 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 ] [ Designated as safety issue: No ]
    Maximum measured concentration of empagliflozin (empa) in plasma at steady state over a uniform dosing interval.

  • 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 ] [ Designated as safety issue: No ]
    Time from last dosing to maximum measured concentration of empagliflozin (empa) in plasma over a uniform dosing interval at steady state, after multiple dosing.

  • 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 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve of empagliflozin (empa) in plasma at steady state over a uniform dosing interval, after multiple dosing

  • 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 ] [ Designated as safety issue: No ]
    Terminal rate constant in plasma at steady state, after multiple dosing.

  • 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 ] [ Designated as safety issue: No ]
    Terminal half-life of empagliflozin (empa) in plasma at steady state, after multiple dosing.

  • 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 ] [ Designated as safety issue: No ]
    Mean residence time of empagliflozin (empa) in the body at steady state after multiple oral administrations

  • 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 ] [ Designated as safety issue: No ]
    Apparent clearance of empagliflozin (empa) in the plasma at steady state following multiple oral dose administration.

  • 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 ] [ Designated as safety issue: No ]
    Apparent volume of distribution during the terminal phase λz at steady state following oral administration after multiple dosing

  • 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 ] [ Designated as safety issue: No ]
    Amount of empagliflozin (empa) eliminated in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.

  • 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after multiple dosing.

  • 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 ] [ Designated as safety issue: No ]
    Accumulation ratio of empagliflozin (empa) based on AUC, after multiple dosing

  • 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 ] [ Designated as safety issue: No ]
    Accumulation ratio of empagliflozin (empa) based on Cmax, after multiple dosing

  • Predose Plasma Concentration Before Planned Dose x (Cpre,x) [ Time Frame: 5 minutes before drug administration ] [ Designated as safety issue: No ]

    Predose plasma concentration of empagliflozin (empa) before planned dose by day.

    This endpoint in steady state is identical to Cmin,ss.


  • 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 ] [ Designated as safety issue: No ]
    Change from day -1 in urinary glucose excretion in a 24 hour collection period per time point.

  • 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 ] [ Designated as safety issue: No ]
    Fasting Plasma Glucose (FPG) change from baseline between day 1 and day 9.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 24
Study Start Date: March 2011
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI10773 low dose Per Os(p.o.)
patient to receive a tablet containing low dose BI10773 Per Os(p.o.) plus one placebo
Drug: Placebo
patient to receive two placebos
Drug: BI10773
patient to receive a tablet containing low dose BI10773 p.o. plus one placebo
Placebo Comparator: Placebo
patient to receive two placebos
Drug: Placebo
patient to receive two placebos
Experimental: BI10773 high dose Per Os(p.o.)
patient to receive a tablet containing high dose BI10773 Per Os(p.o.) plus one placebo
Drug: BI10773
patient to receive a tablet containing high dose BI10773 p.o. plus one placebo
Drug: Placebo
patient to receive two placebos

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. 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
  2. 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
  3. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation.

Exclusion criteria:

  1. Patient who did not discontinue the antidiabetic treatment with insulin or glitazones, DPP-IV at least before 12 weeks before randomization
  2. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast at screening visit
  3. 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316341

Locations
China
1245.44.86001 Boehringer Ingelheim Investigational Site
Beijing, China
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01316341     History of Changes
Other Study ID Numbers: 1245.44
Study First Received: March 15, 2011
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 25, 2014