Hepatic Insufficiency
Conditions
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
Interventions
DRUGBI 1356
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients with hepatic impairment determined by results of screening classified as mild (Child-Pugh class A, score 6 points), moderate (Child-Pugh class B, score 7 to 9 points) or severe (Child-Pugh class C, score 10 to 15 points) * Healthy males and females based on a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests * Subjects in the respective groups were matched with regard to age (±10 years), weight (±20%) and gender * Age 18 to 70 years, inclusive * Body mass index 18.5 to 29.9 kg/m2, inclusive * Creatinine clearance ≥80 mL/min (except for patients with severe hepatic impairment, see
Exclusion criteria
) according to Cockroft & Gault * Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice and local legislation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | 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 | 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 | up to 24 hours after drug administration |
| Cmax (maximum concentration of the analyte in plasma) for patients with severe liver impairment | up to day 6 |
Secondary
| Measure | Time frame |
|---|---|
| Plasma DPP-4 concentration | Day 1 (Baseline) |
| Number of patients with adverse events | up to 47 days |
| Number of patients with clinically significant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR)) | Baseline, up to day 19 |
| Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG) | Baseline, up to day 19 |
| Number of patients with clinically relevant findings in clinical laboratory tests | Baseline, up to day 19 |
| Assessment of tolerability by investigator on a 4-point scale | 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 | 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 | 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 | up to day 12 |
| Plasma protein binding | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | up to day 6 |
| 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 | up to day 12 |
| Model-derived AUCτ,ss for patients with severe liver impairment | up to day 6 |
| Model-derived Cmax,ss for patients with severe liver impairment | up to day 6 |
| Plasma dipeptidyl peptidase-4 (DPP-4) activity | up to day 6 |
Outcome results
None listed