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Pharmacokinetics of Empagliflozin (BI 10773) in Patients With Impaired Liver Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01111318
Recruitment Status : Completed
First Posted : April 27, 2010
Results First Posted : June 13, 2014
Last Update Posted : June 13, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE April 26, 2010
First Posted Date  ICMJE April 27, 2010
Results First Submitted Date  ICMJE May 16, 2014
Results First Posted Date  ICMJE June 13, 2014
Last Update Posted Date June 13, 2014
Study Start Date  ICMJE July 2010
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2014)
  • Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
  • Maximum Measured Concentration (Cmax) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Maximum measured concentration of empagliflozin (empa) in plasma. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Original Primary Outcome Measures  ICMJE
 (submitted: April 26, 2010)
  • maximum measured concentration of the analyte in plasma [ Time Frame: 5 days ]
  • area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity [ Time Frame: 5 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2014)
  • Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h 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. The standard deviation is actually the coefficient of variation.
  • Time From Dosing to Maximum Concentration (Tmax) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration. ]
    Time from dosing to maximum concentration of empagliflozin (empa) in plasma.
  • Terminal Rate Constant (λz) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Terminal rate constant in plasma. The standard deviation is actually the coefficient of variation.
  • Terminal Half-Life (t1/2) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Terminal half-life of empagliflozin (empa) in plasma. The standard deviation is actually the coefficient of variation.
  • Mean Residence Time (MRTpo) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Mean residence time of empagliflozin (empa) in the body. The standard deviation is actually the coefficient of variation.
  • Apparent Clearance After Extravascular Administration (CL/F) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Apparent clearance of empagliflozin (empa) in the plasma after extravascular administration. The standard deviation is actually the coefficient of variation.
  • Apparent Volume of Distribution During the Terminal Phase (Vz/F) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Apparent volume of distribution during the terminal phase (λz). The standard deviation is actually the coefficient of variation.
  • Amount of Empagliflozin That is Eliminated in Urine (Ae0-96) [ Time Frame: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration ]
    Amount of empagliflozin (empa) that is eliminated in urine over the time interval 0 to 96 hours. The standard deviation is actually the coefficient of variation.
  • Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96)) [ Time Frame: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration ]
    Fraction of empagliflozin (empa) excreted unchanged in urine from time points 0 to 96 hours. The standard deviation is actually the coefficient of variation.
  • Renal Clearance After Extravascular Administration (CL R) [ Time Frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration ]
    Renal clearance of empagliflozin (empa) in plasma after extravascular administration. The standard deviation is actually the coefficient of variation.
  • Urinary Glucose Excretion (UGE) [ Time Frame: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration ]
    Urinary glucose excretion, this endpoint was measured using Ae0-96. The standard deviation is actually the coefficient of variation.
  • Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator [ Time Frame: Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days ]
    Clinically relevant abnormalities for physical examination, vital signs, ECG, clinical laboratory tests and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AE).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2010)
  • area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point [ Time Frame: 5 days ]
  • time from last dosing to maximum concentration of the analyte in plasma after the first dose [ Time Frame: 5 days ]
  • terminal rate constant in plasma [ Time Frame: 5 days ]
  • terminal half-life of the analyte in plasma [ Time Frame: 5 days ]
  • mean residence time of the analyte in the body [ Time Frame: 5 days ]
  • apparent clearance of the analyte in the plasma after extravascular administration [ Time Frame: 5 days ]
  • apparent volume of distribution during the terminal phase ¿z [ Time Frame: 5 days ]
  • amount of analyte that is eliminated in urine over the time interval t1 to t2 h [ Time Frame: 5 days ]
  • fraction of analyte excreted unchanged in urine from time points t1 to t2 h [ Time Frame: 5 days ]
  • renal clearance of the analyte in plasma after extravascular administration [ Time Frame: 5 days ]
  • Total urinary glucose excretion will be determined by measuring the glucose concentration in the collected urine and calculating the amount of glucose. [ Time Frame: 5 days ]
  • Physical examination [ Time Frame: 2 days ]
  • Vital signs (Blood pressure and Pulse Rate) [ Time Frame: 3 days ]
  • 12-lead Electrocardiogram [ Time Frame: 3 days ]
  • clinical laboratory tests (haematology, clinical chemistry and urinanalysis) [ Time Frame: 3 days ]
  • Adverse events [ Time Frame: 5 days ]
  • Assessment of tolerability by investigator [ Time Frame: 5 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics of Empagliflozin (BI 10773) in Patients With Impaired Liver Function
Official Title  ICMJE Pharmacokinetics, Safety and Tolerability of BI 10773 50 mg Single Dose in Male and Female Subjects With Different Degrees of Liver Impairment (Child-Pugh Classification A, B and C) as Compared to Male and Female Healthy Subjects (a Non-blinded, Parallel Group Study of Phase I)
Brief Summary The main objective of this study is to assess the effect of mild, moderate and severe hepatic impairment on the pharmacokinetics, safety and tolerability of BI 10773 following oral administration of BI 10773 as a single dose.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatic Insufficiency
  • Healthy
Intervention  ICMJE Drug: BI 10773
2 tablets BI 10773 25 mg single dose
Study Arms  ICMJE Experimental: BI 10773
50 mg single dose
Intervention: Drug: BI 10773
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2010)
36
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date November 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

Healthy males and females. Hepatically impaired male and female subjects. Age: 18 - 75 years, BMI: 18-34 kg/m2 Creatinine clearance >80 mL/min (except for patients with severe hepatic impairment, see exclusion criteria.

Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion criteria:

Healthy subjects (group 1)

  1. Significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders as judged by the investigator.
  2. Relevant gastrointestinal tract surgery.
  3. Diseases of the central nervous system or psychiatric disorders or relevant neurological disorders.
  4. History of relevant orthostatic hypotension, fainting spells or blackouts; systolic blood pressure < 100 or > 160 mm Hg, diastolic blood pressure < 60 or > 100 mm Hg, pulse rate < 50 or > 100 1/min.
  5. Chronic or relevant acute infections.
  6. History of allergy/hypersensitivity.
  7. Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial.
  8. Use within 10 days prior to administration or during the trial of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation
  9. Participation in another trial with an investigational drug within 2 months after a multiple dose study or within 1 month after a single dose study.
  10. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day).
  11. Inability to refrain from smoking when confined to the study site on trial days.
  12. Alcohol abuse, drug abuse.
  13. Veins unsuited for iv puncture on either arm.
  14. Blood donation (more than 100 mL within four weeks prior to administration or during the trial).
  15. Excessive physical activities (within 48 hours prior to trial or during the trial).
  16. Any laboratory value outside the reference range that is of clinical relevance.
  17. Inability to comply with dietary regimen of study centre.
  18. Subjects not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

    Hepatically impaired subjects (group 2-4):

  19. Decompensated gastrointestinal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders.
  20. For patients with severe liver impairment (Child-Pugh C): Severe concurrent renal dysfunction (e.g., due to hepato-renal syndrome) and a creatinine clearance <40mL/min.
  21. Relevant gastrointestinal tract surgery.
  22. Diseases of the central nervous system or psychiatric disorders or relevant neurological disorders.
  23. Chronic or relevant acute infections.
  24. History of allergy/hypersensitivity.
  25. Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial.
  26. Use within 10 days prior to administration or during the trial of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation. Co-medication known to inhibit or induce P-glycoprotein (such as quinidine, cyclosporine, amiodarone) is not allowed. In dubious cases, a case by case decision will be made after consultation with the sponsor.
  27. Participation in another trial with an investigational drug within 2 months after a multiple dose study or within 1 month after a single dose study.
  28. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day).
  29. Inability to refrain from smoking when confined to the study site on trial days.
  30. Alcohol abuse, Drug abuse.
  31. Blood donation (more than 100 mL within four weeks prior to administration or during the trial).
  32. Excessive physical activities (within 48 hours prior to trial or during the trial).
  33. Clinically relevant laboratory abnormalities.
  34. Inability to comply with dietary regimen of study centre.
  35. Subjects not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions

    For female subjects of all groups:

  36. Pregnancy
  37. Positive pregnancy test
  38. No adequate contraception during the study and until 2 months after study completion.
  39. Lactation period.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Romania
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01111318
Other Study ID Numbers  ICMJE 1245.13
2009-017202-36 ( EudraCT Number: EudraCT )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP