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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 1744 CL/BI 54903 XX FDC | Experimental |
| |
| BI 54903 XX | Active Comparator |
| |
| BI 1744 CL | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1744 CL/BI 54903 XX FDC | Drug |
| ||
| BI 54903 XX |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | up to 24 hours after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-t (area under the concentration time curve of the analyte in plasma from 0 to time t) | up to 24 hours after drug administration | |
| Cmax (maximum measured concentration of the analyte in plasma) | for BI 54903 XX |
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Inclusion Criteria:
Exclusion Criteria:
For female subjects:
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|
| BI 1744 CL | Drug |
|
| up to 24 hours after drug administration |
| Cpre (pre-dose concentration of the analyte in plasma (at steady state) | 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) | 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) | up to 24 hours after drug administration |
| AUCτ (area under the plasma concentration-time curve over a uniform dosing interval τ) | 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) | up to 24 hours after drug administration |
| %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) | up to 24 hours after drug administration |
| tmax (time from dosing to the maximum concentration of the analyte in plasma) | up to 24 hours after drug administration |
| λz (terminal rate constant of the analyte in plasma) | up to 24 hours after drug administration |
| t½ (terminal half-life of the analyte in plasma) | up to 24 hours after drug administration |
| MRTih (mean residence time of the analyte in the body after inhaled administration) | 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) | up to 24 hours after drug administration |
| fet1-t2 (fraction of the analyte eliminated in urine from time point t1 to time point t2) | 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) | 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 | 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 | up to 24 hours after drug administration |
| Number of patients with adverse events | up to 16 weeks |
| Assessment of tolerability by investigator on 4-point scale | 28 days after each treatment period |
| ID | Term |
|---|---|
| C549647 | olodaterol |
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