Pharmacokinetics of Empagliflozin (BI 10773) in Patients With Impaired Liver Function
Condition: Hepatic Insufficiency; Healthy
MeSH terms: Hepatic Insufficiency; Liver Failure
Intervention: BI 10773
Intervention description: 2 tablets BI 10773 25 mg single dose
Intervention MeSH terms: Empagliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility 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.