Study to investigate safety and tolerability of single, inhaled doses (2.5 μg, 5 μg, 10 μg, 20 μg and 40 μg) of BI 1744 CL in free dose combination with tiotropium bromide 5 μg (for doses up to and including 20 μg BI 1744 CL) and 10 μg (for doses of 20 μg and 40 μg BI 1744 CL), both administered by Respimat® in healthy male volunteers. Also, to investigate the pharmacokinetics of BI 1744 BS and tiotropium bromide in such combinations, to explore their dose proportionality, and to explore the pharmacodynamic effects of the treatments on selected metabolic and respiratory parameters
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
48
Number of participants with abnormal findings in physical examination
Time frame: up to 12 days after drug administration
Number of participants with abnormal changes in laboratory parameters
Time frame: up to 12 days after drug administration
Number of participants with clinically significant changes in vital signs
blood pressure (BP), pulse rate (PR), respiratory rate (RR)
Time frame: up to 12 days after drug administration
Number of participants with adverse events
Time frame: up to 12 days after drug administration
Number of participants with clinically significant changes in 12-lead ECG
cardiac axis, heart rate, PQ interval, QRS interval, uncorrected QT interval, HR-corrected QT-interval according to Bazett and Fridericia
Time frame: up to 12 days after drug administration
Number of abnormal findings on oropharyngeal inspection
Time frame: up to 24 hours after drug administration
Number of abnormal findings on pulmonary auscultation
Time frame: up to 24 hours after drug administration
Assessment of tolerability by investigator on a 4-point scale
Time frame: 12 days after drug administration
Change in Airway resistance (Raw)
measured by whole-body plethysmography
Time frame: up to 24 hours after drug administration
Change in specific conductance (sGaw)
measured by whole-body plethysmography
Time frame: up to 24 hours after drug administration
Change in Cyclic aminomonophosphate (cAMP)
Time frame: up to 6 hours after drug administration
Change in potassium
Time frame: up to 6 hours after drug administration
Cmax (maximum measured concentration of BI 1744 BS and tiotropium in plasma)
Time frame: up to 96 hours after drug administration
tmax (time from dosing to maximum measured concentration)
Time frame: up to 96 hours after drug administration
AUC0-∞ (area under the concentration-time curve of BI 1744 BS and tiotropium in plasma over the time interval from 0 extrapolated to infinity)
Time frame: up to 96 hours after drug administration
AUC0-tz (area under the concentration-time curve of the analyte salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time frame: up to 96 hours after drug administration
%AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞)
Time frame: up to 96 hours after drug administration
λz (terminal rate constant in plasma)
Time frame: up to 96 hours after drug administration
t1/2 (terminal half-life of BI 1744 BS and tiotropium in plasma)
Time frame: up to 96 hours after drug administration
MRTih (mean residence time of BI 1744 BS and tiotropium in the body after inhalation)
Time frame: up to 96 hours after drug administration
CL/F (apparent clearance of BI 1744 BS and tiotropium in plasma after extravascular administration)
Time frame: up to 96 hours after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time frame: up to 96 hours after drug administration
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Aet1-t2 (amount of BI 1744 BS and tiotropium eliminated in urine from the time point t1 to time point t2)
Time frame: up to 96 hours after drug administration
fet1-t2 (fraction of BI 1744 BS and tiotropium eliminated in urine from time point t1 to time point t2)
Time frame: up to 96 hours after drug administration
CLR,t1-t2 (renal clearance of BI 1744 BS and tiotropium from the time point t1 until the time point t2)
Time frame: up to 96 hours after drug administration