Clinical Trial: Pharmacokinetics and Pharmacodynamics of BI 1356 in Subjects With Different Degrees of Liver Impairment as Compared to Healthy Subjects

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pharmacokinetics and Pharmacodynamics of BI 1356 5 mg Once Daily in Male and Female Subjects With Different Degrees of Liver Impairment (Child Pugh Classification A-C) as Compared to Male and Female H

Brief Summary: To investigate the influence of mild, moderate, and severe liver impairment on the pharmacokinetics and pharmacodynamics of linagliptin in comparison with a control group with normal hepatic function after single or multiple oral administration of 5 mg linagliptin tablets

Detailed Summary:
Sponsor: Boehringer Ingelheim

Current Primary Outcome:

  • AUCτ,ss (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the last dose at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • Cmax,ss (maximum concentration of the analyte in plasma at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the first dose) for patients with severe liver impairment [ Time Frame: up to 24 hours after drug administration ]
  • Cmax (maximum concentration of the analyte in plasma) for patients with severe liver impairment [ Time Frame: up to day 6 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Plasma protein binding [ Time Frame: up to day 12 ]
  • Model-derived AUCτ,ss for patients with severe liver impairment [ Time Frame: up to day 6 ]
  • Model-derived Cmax,ss for patients with severe liver impairment [ Time Frame: up to day 6 ]
  • Plasma dipeptidyl peptidase-4 (DPP-4) activity [ Time Frame: up to day 6 ]
  • Plasma DPP-4 concentration [ Time Frame: Day 1 (Baseline) ]
  • Number of patients with adverse events [ Time Frame: up to 47 days ]
  • Number of patients with clinically significant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR)) [ Time Frame: Baseline, up to day 19 ]
  • Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG) [ Time Frame: Baseline, up to day 19 ]
  • Number of patients with clinically relevant findings in clinical laboratory tests [ Time Frame: Baseline, up to day 19 ]
  • Assessment of tolerability by investigator on a 4-point scale [ Time Frame: day 19 ]
  • tmax(ss) (time from last dose to maximum concentration of the analyte in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • C24(ss) (concentration of the analyte in plasma at steady state after administration of the first or last dose at the end of the dosing interval) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • λz(ss) (terminal rate constant in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • t1/2(ss) (terminal half-life of the analyte in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • MRTpo(ss) (mean residence time of the analyte in the body after oral administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • CL/F(ss) (apparent clearance of the analyte in the plasma after extravascular administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • Vz/F(ss) (apparent volume of distribution during the terminal phase λz following extravascular administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 h after the first dose for multiple dose groups) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to 24 hours after the first dose ]
  • Cmax (maximum concentration of the analyte in plasma after the first dose in multiple dose groups) for healthy patients and patients with mild and moderate liver impairment [ Time Frame: up to day 12 ]
  • %AUCtz-∞ (percentage of area under the concentration-time curve of the analyte in plasma over the time interval from the time of the last quantifiable data point extrapolated to infinity after single dose) in patients with severe liver impairment [ Time Frame: up to day 6 ]
  • AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity after single dose in patients with severe liver impairment) [ Time Frame: up to day 6 ]
  • AUC0-tz (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 after single dose in patients with severe liver impairment) [ Time Frame: up to day 6 ]


Original Secondary Outcome: Same as current

Information By: Boehringer Ingelheim

Dates:
Date Received: July 4, 2014
Date Started: July 2008
Date Completion:
Last Updated: July 4, 2014
Last Verified: July 2014