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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01111318
First received: April 26, 2010
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Liver Diseases
Healthy
Drug: BI 10773
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • maximum measured concentration of the analyte in plasma [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity [ Time Frame: 5 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • time from last dosing to maximum concentration of the analyte in plasma after the first dose [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • terminal rate constant in plasma [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • terminal half-life of the analyte in plasma [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • mean residence time of the analyte in the body [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • apparent clearance of the analyte in the plasma after extravascular administration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • apparent volume of distribution during the terminal phase [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • amount of analyte that is eliminated in urine over the time interval t1 to t2 h [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • fraction of analyte excreted unchanged in urine from time points t1 to t2 h [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • renal clearance of the analyte in plasma after extravascular administration [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Physical examination [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
  • Vital signs (Blood pressure and Pulse Rate) [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
  • 12-lead Electrocardiogram [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
  • clinical laboratory tests (haematology, clinical chemistry and urinanalysis) [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Assessment of tolerability by investigator [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: July 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 10773
50 mg single dose
Drug: BI 10773
2 tablets BI 10773 25 mg single dose

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111318

Locations
Romania
1245.13.40001 Boehringer Ingelheim Investigational Site
Timisoara, Romania
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01111318     History of Changes
Other Study ID Numbers: 1245.13, 2009-017202-36
Study First Received: April 26, 2010
Last Updated: October 4, 2012
Health Authority: Romania: National Medicines Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 17, 2014