Trial Outcomes & Findings for Pharmacokinetics and Safety of BI 1744 CL Plus Tiotropium Bromide in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02231177)
NCT ID: NCT02231177
Last Updated: 2016-01-07
Results Overview
Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)). As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint. The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
COMPLETED
PHASE1
47 participants
Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
2016-01-07
Participant Flow
A randomised, double-blind, 3-way crossover study, each patient received each of the three treatments for 21 days according to randomisation.
Participant milestones
| Measure |
Tio+Olo 5/10 μg, Olo 10 μg, Tio 5 μg
Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
* Olodaterol (Olo) 10 µg.
* Tiotropium (Tio) 5 µg.
|
Tio+Olo 5/10 μg, Tio 5 μg, Olo 10 μg
Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
* Tiotropium 5 µg.
* Olodaterol 10 µg.
|
Olo 10 μg, Tio+Olo 5/10 μg, Tio 5 μg
Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Olodaterol 10 µg.
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
* Tiotropium 5 µg.
|
Olo 10 μg, Tio 5 μg, Tio+Olo 5/10 μg
Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Olodaterol 10 µg.
* Tiotropium 5 µg.
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
|
Tio 5 μg, Tio+Olo 5/10 μg, Olo 10 μg
Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Tiotropium 5 µg.
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
* Olodaterol 10 µg.
|
Tio 5 μg, Olo 10 μg, Tio+Olo 5/10 μg
Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Tiotropium 5 µg.
* Olodaterol 10 µg.
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (21 Days)
STARTED
|
8
|
7
|
8
|
7
|
8
|
9
|
|
Treatment Period 1 (21 Days)
COMPLETED
|
8
|
7
|
8
|
7
|
8
|
9
|
|
Treatment Period 1 (21 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2 (21 Days)
STARTED
|
8
|
7
|
8
|
7
|
8
|
9
|
|
Treatment Period 2 (21 Days)
COMPLETED
|
8
|
7
|
8
|
7
|
8
|
9
|
|
Treatment Period 2 (21 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (21 Days)
STARTED
|
8
|
7
|
8
|
7
|
8
|
9
|
|
Treatment Period 3 (21 Days)
COMPLETED
|
8
|
7
|
8
|
7
|
8
|
9
|
|
Treatment Period 3 (21 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics and Safety of BI 1744 CL Plus Tiotropium Bromide in Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
All Subjects
n=47 Participants
A randomised, active-controlled, double-blind, 3-way crossover study in patients with COPD (chronic obstructive pulmonary disease). All participants received each of the three treatment arms in a randomly assigned order, the three treatments, which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg
* Olodaterol 10 µg.
* Tiotropium 5 µg.
|
|---|---|
|
Age, Continuous
|
59.8 years
STANDARD_DEVIATION 7.4 • n=99 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic (PK) set which included all patients in the treated set who provided at least one of the PK parameters in at least one treatment period and completed the trial without any important protocol violations, it is however restricted to patients with evaluable data for this endpoint.
Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)). As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint. The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=39 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=37 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
AUC(0-1h,ss) of Olodaterol
|
4.67 pg*h/mL
Geometric Coefficient of Variation 32.15
|
4.15 pg*h/mL
Geometric Coefficient of Variation 32.15
|
—
|
PRIMARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=44 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Cmax,ss of Olodaterol
|
5.87 pg/mL
Geometric Coefficient of Variation 27.17
|
5.28 pg/mL
Geometric Coefficient of Variation 27.17
|
—
|
PRIMARY outcome
Timeframe: Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=43 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Ae(0-24h,ss) of Tiotropium
|
900.57 ng
Geometric Coefficient of Variation 20.43
|
918.63 ng
Geometric Coefficient of Variation 20.43
|
—
|
SECONDARY outcome
Timeframe: Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Amount of Olodaterol that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=46 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=43 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Ae(0-24h,ss) of Olodaterol
|
360.98 ng
Geometric Coefficient of Variation 19.85
|
344.17 ng
Geometric Coefficient of Variation 19.85
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=6 h at steady state (AUC(0-6h,ss)). As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Tiotropium. Based on the given definition AUC(0-6h,ss) was selected as secondary endpoint. The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=36 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=35 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
AUC(0-6h,ss) of Tiotropium
|
29.97 pg*h/mL
Geometric Coefficient of Variation 19.81
|
33.24 pg*h/mL
Geometric Coefficient of Variation 19.81
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=45 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Cmax,ss of Tiotropium
|
15.55 pg/mL
Geometric Coefficient of Variation 29.92
|
16.15 pg/mL
Geometric Coefficient of Variation 29.92
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Area under the concentration time curve of Olodaterol in plasma over the time interval 0 to 2 hours at steady state (AUC(0-2h,ss)). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=37 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=30 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
AUC(0-2h,ss) of Olodaterol
|
8.52 pg*h/mL
Geometric Coefficient of Variation 21.33
|
8.36 pg*h/mL
Geometric Coefficient of Variation 21.33
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=4 h at steady state (AUC(0-4h,ss)). The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=44 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=39 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
AUC(0-4h,ss) of Tiotropium
|
21.92 pg*h/mL
Geometric Coefficient of Variation 22.61
|
24.00 pg*h/mL
Geometric Coefficient of Variation 22.61
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Olodaterol. The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=44 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
AUC(0-tz,ss) of Olodaterol
|
12.20 pg*h/mL
Geometric Coefficient of Variation 96.12
|
9.25 pg*h/mL
Geometric Coefficient of Variation 96.12
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Tiotropium. The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=45 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
AUC(0-tz,ss) of Tiotropium
|
32.67 pg*h/mL
Geometric Coefficient of Variation 72.08
|
32.91 pg*h/mL
Geometric Coefficient of Variation 72.08
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Time from dosing to the maximum concentration of Olodaterol in plasma at steady state (tmax,ss).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=44 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Tmax,ss of Olodaterol
|
0.25 h
Interval 0.05 to 2.02
|
0.25 h
Interval 0.083 to 1.0
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Time from dosing to the maximum concentration of Tiotropium in plasma at steady state (tmax,ss).
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=45 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Tmax,ss of Tiotropium
|
0.083 h
Interval 0.033 to 0.333
|
0.083 h
Interval 0.033 to 0.333
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Fraction of Olodaterol eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)). The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=46 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=43 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
fe(0-24,ss) of Olodaterol
|
3.62 percentage of olodaterol dose
Geometric Coefficient of Variation 43.8
|
3.57 percentage of olodaterol dose
Geometric Coefficient of Variation 47.7
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Fraction of Tiotropium eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)). The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=43 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
fe(0-24,ss) of Tiotropium
|
18.2 percentage of tiotropium dose
Geometric Coefficient of Variation 41.5
|
18.6 percentage of tiotropium dose
Geometric Coefficient of Variation 46.1
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss). The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=44 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Cmin,ss of Olodaterol
|
2.30 pg/mL
Geometric Coefficient of Variation 12.6
|
2.26 pg/mL
Geometric Coefficient of Variation 12.0
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss). The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=45 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Cmin,ss of Tiotropium
|
2.95 pg/mL
Geometric Coefficient of Variation 14.9
|
2.89 pg/mL
Geometric Coefficient of Variation 9.84
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=45 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=44 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Tmin,ss of Olodaterol
|
2.00 h
Interval 0.0 to 24.0
|
1.01 h
Interval 0.0 to 12.0
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=45 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Tmin,ss of Tiotropium
|
6.00 h
Interval 0.0 to 24.0
|
8.00 h
Interval 0.33 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333\_8), C(0.333\_14,ss) and C(0.333\_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21. The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=43 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=40 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Concentration of Olodaterol in Plasma
C(0.333_8) (N=38, 34)
|
5.09 pg/mL
Geometric Coefficient of Variation 48.0
|
4.48 pg/mL
Geometric Coefficient of Variation 48.2
|
—
|
|
Concentration of Olodaterol in Plasma
C(0.333_14,ss) (N=41, 38)
|
5.13 pg/mL
Geometric Coefficient of Variation 41.4
|
4.66 pg/mL
Geometric Coefficient of Variation 52.5
|
—
|
|
Concentration of Olodaterol in Plasma
C(0.333_21,ss) (N=43, 40)
|
5.23 pg/mL
Geometric Coefficient of Variation 53.7
|
4.80 pg/mL
Geometric Coefficient of Variation 54.5
|
—
|
SECONDARY outcome
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.Population: Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.
Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333\_8), C(0.333\_14,ss) and C(0.333\_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21. The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=46 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=44 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Concentration of Tiotropium in Plasma
C(0.333_14,ss) (N=43, 40)
|
9.08 pg/mL
Geometric Coefficient of Variation 53.3
|
9.02 pg/mL
Geometric Coefficient of Variation 60.3
|
—
|
|
Concentration of Tiotropium in Plasma
C(0.333_8) (N=40, 38)
|
8.90 pg/mL
Geometric Coefficient of Variation 60.7
|
9.58 pg/mL
Geometric Coefficient of Variation 52.9
|
—
|
|
Concentration of Tiotropium in Plasma
C(0.333_21,ss) (N=46, 44)
|
8.34 pg/mL
Geometric Coefficient of Variation 53.2
|
9.21 pg/mL
Geometric Coefficient of Variation 58.8
|
—
|
SECONDARY outcome
Timeframe: 0:30 and 1:00 h after drug administration on the first day of each treatment periodPopulation: Treated Set.
Mean change from baseline in forced vital capacity (FVC). Pulmonary function test. The baseline value was measured pre-dose on day 1 of the first treatment period.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=47 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
n=47 Participants
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
FVC Change From Baseline
0:30 h after drug administration (N=47, 47, 47)
|
0.485 L
Standard Deviation 0.354
|
0.450 L
Standard Deviation 0.406
|
0.436 L
Standard Deviation 0.321
|
|
FVC Change From Baseline
1:00 h after drug administration (N=47, 46, 47)
|
0.547 L
Standard Deviation 0.409
|
0.522 L
Standard Deviation 0.375
|
0.470 L
Standard Deviation 0.387
|
SECONDARY outcome
Timeframe: 0:30 and 1:00 h after drug administration on the first day of each treatment periodPopulation: Treated Set.
Mean change from baseline in forced expiratory volume in one second (FEV1). Pulmonary function test. The baseline value was measured pre-dose on day 1 of the first treatment period.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=47 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
n=47 Participants
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
FEV1 Change From Baseline
0:30 h after drug administration (N=47, 47, 47)
|
0.275 L
Standard Deviation 0.202
|
0.292 L
Standard Deviation 0.233
|
0.271 L
Standard Deviation 0.211
|
|
FEV1 Change From Baseline
1:00 h after drug administration (N=47, 46, 47)
|
0.335 L
Standard Deviation 0.250
|
0.357 L
Standard Deviation 0.237
|
0.284 L
Standard Deviation 0.206
|
SECONDARY outcome
Timeframe: From drug administration until 14 days following the last drug administrationPopulation: Treated Set. All randomised patients who received at least one dose of trial medication were included in the treated set.
Clinically relevant abnormalities in vital signs (blood pressure and pulse rate), physical examination, blood chemistry, haematology, urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Any adverse events which occurred within 14 days following the last drug administration were assigned to the last study treatment administered.
Outcome measures
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=47 Participants
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
n=47 Participants
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Tiotropium+Olodaterol 5/10 μg
Olodaterol 10 µg
Tiotropium 5 µg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tiotropium+Olodaterol 5/10 μg
n=47 participants at risk
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Olodaterol 10 µg
n=47 participants at risk
Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
Tiotropium 5 µg
n=47 participants at risk
Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
4.3%
2/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
8.5%
4/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
6.4%
3/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
|
Nervous system disorders
Headache
|
6.4%
3/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
6.4%
3/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
10.6%
5/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.1%
1/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
10.6%
5/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
2.1%
1/47 • From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.
At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER