The main objective of this study was to investigate the influence of mild and moderate liver impairment on the pharmacokinetics, safety and selected pharmacodynamic parameters of BI 1744 CL in comparison to a control group with normal hepatic function after single orally inhaled administration of BI 1744 CL with the Respimat® Inhaler.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
AUC0-∞,norm (dose-normalized area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
Cmax,norm (dose-normalized maximum concentration of the analyte in plasma)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
Cmax (maximum concentration of the analyte in plasma)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
AUC0-tz(,norm) ((dose-normalized ) 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: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
%AUCtz-∞ (the percentage of the AUC 0-∞ that is obtained by extrapolation)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
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λz (terminal rate constant in plasma)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
t1/2 (terminal half-life of the analyte in plasma)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
MRTih (mean residence time of the analyte in plasma in the body after inhalation)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to t2)
Time frame: before and 0-8, 8-12, 12-24, 24-48, 48-72 hours following drug administration
fet1-t2 (fraction of analyte excreted in urine from the time point t1 to t2)
Time frame: before and 0-8, 8-12, 12-24, 24-48, 48-72 hours following drug administration
CLR,t1-t2 (renal clearance of the analyte in urine from the time point t1 to t2)
Time frame: before and 0-8, 8-12, 12-24, 24-48, 48-72 hours following drug administration
Plasma protein binding
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
CL (total clearance of the analyte in plasma after intravascular administration)
Time frame: before and 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, and 72:00 hours following drug administration
Number of patients with abnormal findings in physical examination
Time frame: Baseline, day 14
Number of patients with clinically significant changes in vital signs (blood pressure (BP), pulse rate (PR))
Time frame: Baseline, up to day 14
Number of patients with abnormal findings in 12-lead ECG (electrocardiogram)
Time frame: Baseline, up to day 14
Number of patients with clinically significant changes in clinical laboratory tests
Time frame: Baseline, up to day 14
Number of patients with adverse events
Time frame: 5 weeks
Assessment of tolerability by the investigator on a 4-point scale
Time frame: Day 14