The primary objective of this study was to compare the systemic exposure of BI 1744 BS and CD 1857 XX (the active metabolite of the pro-drug BI 54903 XX) at steady state following inhalation of the fixed dose combination (FDC) of 6.2 μg BI 1744 CL plus 727.3 μg BI 54903 XX (as ethanolic solution for inhalation, EIS) with the systemic exposure following inhalation of the mono compounds of 10 μg BI 1744 CL (as aqueous solution for inhalation, AIS) and 727.3 μg BI 54903 XX (EIS), respectively, when administered once-daily via Respimat® Inhaler (Respimat® A for AIS and Respimat® B for EIS) for 14 days in healthy volunteers. Secondary objectives were to compare exposure to BI 1744 BS and CD 1857 XX after a single dose of the BI 1744 CL/BI 54903 XX (6.2 μg/727.3 μg) FDC and the mono compounds, respectively; to compare exposure to BI 54903 XX after a single dose and at steady state after multiple doses of the BI 1744 CL/BI 54903 XX (6.2 μg/727.3 μg) FDC and the mono compounds, respectively; to compare the safety and tolerability of BI 1744 CL and BI 54903 XX when administered as BI 1744 CL/BI 54903 XX (6.2 μg/727.3 μg) FDC and as the mono compounds, respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
AUC0-t,ss (area under the concentration time curve of the analyte in plasma from 0 to time t at steady state)
for BI 1744 BS and CD 1857 XX
Time frame: up to 24 hours after drug administration
Cmax,ss (maximum measured concentration of the analyte in plasma at steady state)
for BI 1744 BS and CD 1857 XX
Time frame: up to 24 hours after drug administration
AUC0-t (area under the concentration time curve of the analyte in plasma from 0 to time t)
Time frame: up to 24 hours after drug administration
Cmax (maximum measured concentration of the analyte in plasma)
for BI 54903 XX
Time frame: up to 24 hours after drug administration
Cpre (pre-dose concentration of the analyte in plasma (at steady state)
Time frame: up to 24 hours after drug administration
AUCt1-t2 (area under the concentration time curve of the analyte in plasma over the time interval t1 to t2)
Time frame: up to 24 hours after drug administration
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)
Time frame: up to 24 hours after drug administration
AUCτ (area under the plasma concentration-time curve over a uniform dosing interval τ)
Time frame: up to 24 hours after 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: up to 24 hours after drug administration
%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
Time frame: up to 24 hours after drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Time frame: up to 24 hours after drug administration
λz (terminal rate constant of the analyte in plasma)
Time frame: up to 24 hours after drug administration
t½ (terminal half-life of the analyte in plasma)
Time frame: up to 24 hours after drug administration
MRTih (mean residence time of the analyte in the body after inhaled administration)
Time frame: up to 24 hours after drug administration
Aet1-t2 (amount of the analyte that is eliminated in urine from the time point t1 to time point t2)
Time frame: up to 24 hours after drug administration
fet1-t2 (fraction of the analyte eliminated in urine from time point t1 to time point t2)
Time frame: up to 24 hours after drug administration
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)
Time frame: up to 24 hours after drug administration
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
For BI 1744 BS and BI 54903 XX only
Time frame: up to 24 hours after drug administration
Vz/F (apparent volume of distribution of the analyte during the terminal phase following an extravascular dose)
For BI 1744 BS and BI 54903 XX only
Time frame: up to 24 hours after drug administration
Number of patients with adverse events
Time frame: up to 16 weeks
Assessment of tolerability by investigator on 4-point scale
Time frame: 28 days after each treatment period
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