A Randomised, Open-label, Parallel-group Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After 3 Weeks Once Daily Treatment in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

CLR,t1-t2,ss (Olodaterol)

时间窗: from 0 to 4 hours following drug administration on day 21

Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

AUC0-tz,ss (Tiotropium)

时间窗: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

AUCt1-t2,ss (Olodaterol)

时间窗: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

AUC0-tz,ss (Olodaterol)

时间窗: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

Tmax,ss (Olodaterol)

时间窗: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21

Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

Cmax,ss (Olodaterol)

时间窗: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21

Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

Aet1-t2,ss (Olodaterol)

时间窗: from 0 to 4 hours following drug administration on day 21

Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

fe t1-t2,ss (Olodaterol)

时间窗: from 0 to 4 hours following drug administration on day 21

Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

Aet1-t2,ss (Tiotropium)

时间窗: from 0 to 4 hours following drug administration on day 21

Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

fe t1-t2,ss (Tiotropium)

时间窗: from 0 to 4 hours following drug administration on day 21

Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

CLR,t1-t2,ss (Tiotropium)

时间窗: from 0 to 4 hours following drug administration on day 21

Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type. Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).

Cmax,ss (Tiotropium)

时间窗: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21

Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

AUCt1-t2,ss (Tiotropium)

时间窗: 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21

Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

Tmax,ss (Tiotropium)

时间窗: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21

Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss). Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.