Trial Outcomes & Findings for Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Patients With COPD. (NCT NCT00452400)
NCT ID: NCT00452400
Last Updated: 2014-06-27
Results Overview
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
COMPLETED
PHASE2
409 participants
Baseline and 4 weeks
2014-06-27
Participant Flow
409 patients were enrolled to the study, however 4 patients were assigned incorrect medication, so these patients were re-randomised, so only 405 patients actually started the study.
Participant milestones
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
79
|
81
|
80
|
86
|
79
|
|
Overall Study
COMPLETED
|
74
|
80
|
73
|
85
|
76
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
7
|
1
|
3
|
Reasons for withdrawal
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
5
|
0
|
2
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
0
|
0
|
0
|
|
Overall Study
Other reasons not listed above
|
0
|
0
|
0
|
1
|
1
|
Baseline Characteristics
Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Patients With COPD.
Baseline characteristics by cohort
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
Total
n=405 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
62.66 years
STANDARD_DEVIATION 9.74 • n=99 Participants
|
63.81 years
STANDARD_DEVIATION 8.63 • n=107 Participants
|
63.25 years
STANDARD_DEVIATION 9.47 • n=206 Participants
|
63.55 years
STANDARD_DEVIATION 7.92 • n=7 Participants
|
63.19 years
STANDARD_DEVIATION 9.00 • n=31 Participants
|
63.30 years
STANDARD_DEVIATION 8.92 • n=30 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
35 Participants
n=7 Participants
|
33 Participants
n=31 Participants
|
171 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=99 Participants
|
42 Participants
n=107 Participants
|
56 Participants
n=206 Participants
|
51 Participants
n=7 Participants
|
46 Participants
n=31 Participants
|
234 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: Baseline and 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Trough FEV1 Response After 4 Weeks
|
-0.014 Liter
Standard Error 0.021
|
0.046 Liter
Standard Error 0.021
|
0.082 Liter
Standard Error 0.021
|
0.109 Liter
Standard Error 0.021
|
0.118 Liter
Standard Error 0.021
|
SECONDARY outcome
Timeframe: Baseline and 1 weekPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Trough FEV1 Response After 1 Week
|
-0.029 Liter
Standard Error 0.019
|
0.059 Liter
Standard Error 0.018
|
0.108 Liter
Standard Error 0.019
|
0.099 Liter
Standard Error 0.018
|
0.140 Liter
Standard Error 0.019
|
SECONDARY outcome
Timeframe: Baseline and 2 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Trough FEV1 Response After 2 Weeks
|
-0.023 Liter
Standard Error 0.020
|
0.062 Liter
Standard Error 0.020
|
0.099 Liter
Standard Error 0.020
|
0.102 Liter
Standard Error 0.020
|
0.105 Liter
Standard Error 0.020
|
SECONDARY outcome
Timeframe: Baseline and 1 weekPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Trough FVC Response After 1 Week
|
-0.020 Liter
Standard Error 0.033
|
0.090 Liter
Standard Error 0.033
|
0.154 Liter
Standard Error 0.033
|
0.149 Liter
Standard Error 0.032
|
0.151 Liter
Standard Error 0.033
|
SECONDARY outcome
Timeframe: Baseline and 2 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Trough FVC Response After 2 Weeks
|
-0.000 Liter
Standard Error 0.040
|
0.090 Liter
Standard Error 0.040
|
0.171 Liter
Standard Error 0.040
|
0.149 Liter
Standard Error 0.039
|
0.148 Liter
Standard Error 0.040
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Trough FVC Response After 4 Weeks
|
-0.026 Liter
Standard Error 0.040
|
0.068 Liter
Standard Error 0.040
|
0.136 Liter
Standard Error 0.040
|
0.146 Liter
Standard Error 0.039
|
0.153 Liter
Standard Error 0.040
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
|
0.013 Liter
Standard Error 0.025
|
0.154 Liter
Standard Error 0.024
|
0.175 Liter
Standard Error 0.025
|
0.226 Liter
Standard Error 0.024
|
0.228 Liter
Standard Error 0.025
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Peak FEV1 (0-3h) Response After 4 Weeks
|
0.078 Liter
Standard Error 0.026
|
0.242 Liter
Standard Error 0.026
|
0.247 Liter
Standard Error 0.026
|
0.295 Liter
Standard Error 0.025
|
0.303 Liter
Standard Error 0.026
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
|
0.009 Liter
Standard Error 0.044
|
0.271 Liter
Standard Error 0.043
|
0.292 Liter
Standard Error 0.044
|
0.320 Liter
Standard Error 0.042
|
0.313 Liter
Standard Error 0.044
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Peak (0-3h) will be the maximum post-dose value during the first 3 hours. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Peak FVC (0-3h) Response After 4 Weeks
|
0.152 Liter
Standard Error 0.046
|
0.440 Liter
Standard Error 0.046
|
0.432 Liter
Standard Error 0.046
|
0.449 Liter
Standard Error 0.044
|
0.438 Liter
Standard Error 0.046
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours postdose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1
|
0.031 Liter
Standard Error 0.017
|
0.165 Liter
Standard Error 0.017
|
0.203 Liter
Standard Error 0.017
|
0.236 Liter
Standard Error 0.017
|
0.234 Liter
Standard Error 0.017
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1
|
-0.000 Liter
Standard Error 0.022
|
0.186 Liter
Standard Error 0.022
|
0.215 Liter
Standard Error 0.022
|
0.218 Liter
Standard Error 0.021
|
0.247 Liter
Standard Error 0.022
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2
|
0.006 Liter
Standard Error 0.024
|
0.166 Liter
Standard Error 0.024
|
0.200 Liter
Standard Error 0.024
|
0.209 Liter
Standard Error 0.023
|
0.211 Liter
Standard Error 0.024
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.Means are adjusted using a mixed effects model with baseline,treatment and centre (centre random, all other effects fixed).
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Peak FEV1 (0-3h) Response At Day 1
|
0.104 Liter
Standard Error 0.021
|
0.259 Liter
Standard Error 0.021
|
0.288 Liter
Standard Error 0.021
|
0.335 Liter
Standard Error 0.020
|
0.335 Liter
Standard Error 0.021
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 weekPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Peak FEV1 (0-3h) Response After 1 Weeks
|
0.062 Liter
Standard Error 0.024
|
0.264 Liter
Standard Error 0.023
|
0.293 Liter
Standard Error 0.024
|
0.295 Liter
Standard Error 0.023
|
0.321 Liter
Standard Error 0.024
|
SECONDARY outcome
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Peak FEV1 (0-3h) Response After 2 Weeks
|
0.079 Liter
Standard Error 0.025
|
0.243 Liter
Standard Error 0.025
|
0.267 Liter
Standard Error 0.025
|
0.282 Liter
Standard Error 0.024
|
0.280 Liter
Standard Error 0.025
|
SECONDARY outcome
Timeframe: baseline and day1Population: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Outcome measures
| Measure |
Placebo
n=73 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=75 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=79 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=72 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=73 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1
|
0.019 Liter
Standard Error 0.028
|
0.064 Liter
Standard Error 0.028
|
0.166 Liter
Standard Error 0.027
|
0.195 Liter
Standard Error 0.028
|
0.171 Liter
Standard Error 0.028
|
SECONDARY outcome
Timeframe: Baseline and 1 weekPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Outcome measures
| Measure |
Placebo
n=73 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=75 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=79 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=72 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=73 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week
|
-0.018 Liter
Standard Error 0.030
|
0.067 Liter
Standard Error 0.030
|
0.156 Liter
Standard Error 0.029
|
0.132 Liter
Standard Error 0.030
|
0.118 Liter
Standard Error 0.030
|
SECONDARY outcome
Timeframe: Baseline and 2 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Outcome measures
| Measure |
Placebo
n=73 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=75 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=79 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=72 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=73 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks
|
0.006 Liter
Standard Error 0.031
|
0.059 Liter
Standard Error 0.031
|
0.135 Liter
Standard Error 0.030
|
0.105 Liter
Standard Error 0.031
|
0.098 Liter
Standard Error 0.031
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.
Outcome measures
| Measure |
Placebo
n=73 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=75 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=79 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=72 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=73 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks
|
0.005 Liter
Standard Error 0.031
|
0.058 Liter
Standard Error 0.031
|
0.134 Liter
Standard Error 0.030
|
0.145 Liter
Standard Error 0.032
|
0.094 Liter
Standard Error 0.031
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Baseline PEFR was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.
Outcome measures
| Measure |
Placebo
n=78 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=79 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=77 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks
|
212.69 Liter/minute
Standard Error 4.431
|
226.39 Liter/minute
Standard Error 4.367
|
233.97 Liter/minute
Standard Error 4.425
|
250.77 Liter/minute
Standard Error 4.244
|
235.75 Liter/minute
Standard Error 4.471
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.
Outcome measures
| Measure |
Placebo
n=78 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=77 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=75 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Weekly Mean Evening PEFR After 4 Weeks
|
224.65 Liter/minute
Standard Error 4.581
|
235.09 Liter/minute
Standard Error 4.507
|
246.98 Liter/minute
Standard Error 4.621
|
262.88 Liter/minute
Standard Error 4.376
|
250.06 Liter/minute
Standard Error 4.678
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Full analysis set (FAS) is defined as all randomized patients who received at least one dose of treatment and had baseline data for at least one endpoint.
Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol (albuterol))
Outcome measures
| Measure |
Placebo
n=78 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=79 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=77 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
|
2.914 Number of puffs
Standard Error 0.260
|
2.393 Number of puffs
Standard Error 0.255
|
3.052 Number of puffs
Standard Error 0.258
|
1.949 Number of puffs
Standard Error 0.248
|
2.500 Number of puffs
Standard Error 0.262
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=44 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=58 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Area Under Curve From 0 to 3 Hours (AUC0-3)
Olodaterol (N=0;0;0;29;58)
|
—
|
—
|
—
|
13.3 Picogram*hours/milliliter
Geometric Coefficient of Variation 37.9
|
20.3 Picogram*hours/milliliter
Geometric Coefficient of Variation 56.0
|
|
Area Under Curve From 0 to 3 Hours (AUC0-3)
Olodaterol glucuronide (N=0;0;0;44;44)
|
—
|
—
|
—
|
11.6 Picogram*hours/milliliter
Geometric Coefficient of Variation 52.8
|
21.1 Picogram*hours/milliliter
Geometric Coefficient of Variation 67.8
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=54 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=71 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=69 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Maximum Concentration (Cmax)
Olodaterol (N=0;0;40;71;69)
|
—
|
—
|
3.58 Picogram/milliliter
Geometric Coefficient of Variation 51.4
|
5.45 Picogram/milliliter
Geometric Coefficient of Variation 63.5
|
12.2 Picogram/milliliter
Geometric Coefficient of Variation 76.0
|
|
Maximum Concentration (Cmax)
Olodaterol glucuronide (N=0;0;54;71;66)
|
—
|
—
|
3.94 Picogram/milliliter
Geometric Coefficient of Variation 97.5
|
5.24 Picogram/milliliter
Geometric Coefficient of Variation 97.4
|
10.6 Picogram/milliliter
Geometric Coefficient of Variation 88.1
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=54 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=71 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=69 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Time From Dosing to the Maximum Concentration (Tmax)
Olodaterol (N=0;0;40;71;69)
|
—
|
—
|
0.167 hours
Interval 0.083 to 1.0
|
0.183 hours
Interval 0.05 to 1.58
|
0.200 hours
Interval 0.033 to 1.27
|
|
Time From Dosing to the Maximum Concentration (Tmax)
Olodaterol glucuronide (N=0;0;54;71;66)
|
—
|
—
|
2.95 hours
Interval 0.083 to 3.38
|
3.00 hours
Interval 0.083 to 3.92
|
3.00 hours
Interval 0.083 to 3.6
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3 at steady state.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=55 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=69 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=70 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
Olodaterol (N=0;0;0;63;70)
|
—
|
—
|
NA Picogram*hours/milliliter
Geometric Coefficient of Variation NA
No patients analyzed.
|
15.6 Picogram*hours/milliliter
Geometric Coefficient of Variation 49.9
|
27.7 Picogram*hours/milliliter
Geometric Coefficient of Variation 64.3
|
|
Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
Olodaterol glucuronide (N=0;0;55;69;63)
|
—
|
—
|
9.29 Picogram*hours/milliliter
Geometric Coefficient of Variation 43.3
|
11.4 Picogram*hours/milliliter
Geometric Coefficient of Variation 69.0
|
23.9 Picogram*hours/milliliter
Geometric Coefficient of Variation 68.9
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=6 at steady state.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=32 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=55 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=69 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
Olodaterol (N=0;0;0;55;69)
|
—
|
—
|
NA Picogram*hours/milliliter
Geometric Coefficient of Variation NA
No patients analyzed.
|
29.7 Picogram*hours/milliliter
Geometric Coefficient of Variation 43.0
|
46.4 Picogram*hours/milliliter
Geometric Coefficient of Variation 57.3
|
|
Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
Olodaterol glucuronide (N=0;0;32;50;48)
|
—
|
—
|
21.4 Picogram*hours/milliliter
Geometric Coefficient of Variation 40.6
|
25.6 Picogram*hours/milliliter
Geometric Coefficient of Variation 60.2
|
49.4 Picogram*hours/milliliter
Geometric Coefficient of Variation 61.0
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=24 at steady state.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=39 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=60 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
Olodaterol
|
—
|
—
|
—
|
104 Picogram*hours/milliliter
Geometric Coefficient of Variation 40.9
|
145 Picogram*hours/milliliter
Geometric Coefficient of Variation 55.1
|
|
Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
Olodaterol glucuronide
|
—
|
—
|
—
|
NA Picogram*hours/milliliter
Geometric Coefficient of Variation NA
No patients analyzed.
|
NA Picogram*hours/milliliter
Geometric Coefficient of Variation NA
No patients analyzed.
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=60 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=72 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=72 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Maximum Concentration at Steady State (Cmax,ss)
Olodaterol glucuronide (N=0;0;60;72;66)
|
—
|
—
|
4.90 Picogram/milliliter
Geometric Coefficient of Variation 49.8
|
5.55 Picogram/milliliter
Geometric Coefficient of Variation 65.2
|
11.1 Picogram/milliliter
Geometric Coefficient of Variation 81.0
|
|
Maximum Concentration at Steady State (Cmax,ss)
Olodaterol (N=0;0;46;72;72)
|
—
|
—
|
4.02 Picogram/milliliter
Geometric Coefficient of Variation 46.7
|
7.13 Picogram/milliliter
Geometric Coefficient of Variation 63.8
|
14.1 Picogram/milliliter
Geometric Coefficient of Variation 83.4
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.
tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.
Outcome measures
| Measure |
Placebo
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=60 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=72 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=72 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
Olodaterol (N=0;0;46;72;72)
|
—
|
—
|
0.192 hours
Interval 0.083 to 1.02
|
0.200 hours
Interval 0.05 to 1.02
|
0.200 hours
Interval 0.083 to 1.0
|
|
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
Olodaterol glucuronide (N=0;0;60;72;66)
|
—
|
—
|
3.00 hours
Interval 0.1 to 6.13
|
3.00 hours
Interval 0.667 to 6.12
|
3.00 hours
Interval 0.0 to 6.03
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Treated set including all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=81 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=80 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=86 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=79 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Blood creatine phosphokinase increased
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Electrocardiogram QT prolonged
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
2 participants
|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Gamma-glutamyltransferase increased
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Atrioventricular block first degree
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Sinus arrhythmia
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Tachycardia
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
Palpitations
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and day 29Population: Treated set includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value.
Outcome measures
| Measure |
Placebo
n=64 Participants
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg qd
n=73 Participants
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg qd
n=67 Participants
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg qd
n=75 Participants
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg qd
n=66 Participants
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Laboratory Testing: Average Change From Baseline of Potassium
|
0.97 mmol/L
Inter-Quartile Range NA • Interval 0.93 to 1.01
|
0.99 mmol/L
Inter-Quartile Range NA • Interval 0.94 to 1.05
|
0.98 mmol/L
Inter-Quartile Range NA • Interval 0.94 to 1.04
|
0.97 mmol/L
Inter-Quartile Range NA • Interval 0.92 to 1.02
|
0.98 mmol/L
Inter-Quartile Range NA • Interval 0.93 to 1.02
|
Adverse Events
Placebo
Olo 2 mcg
Olo 5 mcg
Olo 10 mcg
Olo 20 mcg
Serious adverse events
| Measure |
Placebo
n=79 participants at risk
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg
n=81 participants at risk
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg
n=80 participants at risk
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg
n=86 participants at risk
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg
n=79 participants at risk
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
1.3%
1/79 • 4 weeks
|
|
Infections and infestations
Bronchitis
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
1.2%
1/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
1.2%
1/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
1.3%
1/79 • 4 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
1.2%
1/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
1.2%
1/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
1.2%
1/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/79 • 4 weeks
|
1.2%
1/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/79 • 4 weeks
|
1.2%
1/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/79 • 4 weeks
|
0.00%
0/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
1.2%
1/86 • 4 weeks
|
1.3%
1/79 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/79 • 4 weeks
|
1.2%
1/81 • 4 weeks
|
0.00%
0/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
0.00%
0/79 • 4 weeks
|
Other adverse events
| Measure |
Placebo
n=79 participants at risk
Matching Placebo delivered by the Respimat Inhaler.
|
Olo 2 mcg
n=81 participants at risk
Olodaterol 2 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 5 mcg
n=80 participants at risk
Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 10 mcg
n=86 participants at risk
Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
|
Olo 20 mcg
n=79 participants at risk
Olodaterol 20 mcg qd (morning) delivered by the Respimat Inhaler.
|
|---|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
1.3%
1/79 • 4 weeks
|
2.5%
2/81 • 4 weeks
|
7.5%
6/80 • 4 weeks
|
4.7%
4/86 • 4 weeks
|
2.5%
2/79 • 4 weeks
|
|
Nervous system disorders
Headache
|
5.1%
4/79 • 4 weeks
|
3.7%
3/81 • 4 weeks
|
1.2%
1/80 • 4 weeks
|
3.5%
3/86 • 4 weeks
|
1.3%
1/79 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.5%
2/79 • 4 weeks
|
4.9%
4/81 • 4 weeks
|
7.5%
6/80 • 4 weeks
|
2.3%
2/86 • 4 weeks
|
2.5%
2/79 • 4 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.6%
6/79 • 4 weeks
|
3.7%
3/81 • 4 weeks
|
2.5%
2/80 • 4 weeks
|
0.00%
0/86 • 4 weeks
|
3.8%
3/79 • 4 weeks
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER