Trial Outcomes & Findings for Effect of Treatment BI 1744 CL (5 and 10 mcg) Versus Placebo on Exercise Endurance Time During Constant Work Rate Cycle Ergometry I (NCT NCT01040130)

Results Overview

Primary endpoint was endurance time during constant work rate ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. Mixed effects model on log10 transformation data. Adjusted means are back transformed to report as geometric means. Standard errors (SEs) are calculated using the delta method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

151 participants

Primary outcome timeframe

6 weeks

Results posted on

2014-07-08

Participant Flow

This was a randomised, double-blind, placebo-controlled, 3-way crossover trial. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.

Participant milestones

Participant milestones
Measure	Placebo / Olo 5mcg / Olo 10mcg Patients were administered placebo in the first period, Olodaterol 5 mcg qd in the second period and Olodaterol 10 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Placebo / Olo 10mcg / Olo 5mcg Patients were administered placebo in the first period, Olodaterol 10 mcg qd in the second period and Olodaterol 5 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg / Placebo / Olo 10mcg Patients were administered Olodaterol 5 mcg qd in the first period, placebo in the second period and Olodaterol 10 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg / Olo 10mcg / Placebo Patients were administered Olodaterol 5 mcg qd in the first period, Olodaterol 10 mcg qd in the second period and placebo in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg / Placebo / Olo 5mcg Patients were administered Olodaterol 10 mcg qd in the first period, placebo in the second period and Olodaterol 5 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg / Olo 5mcg / Placebo Patients were administered Olodaterol 10 mcg qd in the first period, Olodaterol 5 mcg qd in the second period and placebo in the third period. Olodaterol was administered via the Respimat inhaler.
Overall Study STARTED	25	25	25	25	25	26
Overall Study COMPLETED	22	22	23	20	25	22
Overall Study NOT COMPLETED	3	3	2	5	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo / Olo 5mcg / Olo 10mcg Patients were administered placebo in the first period, Olodaterol 5 mcg qd in the second period and Olodaterol 10 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Placebo / Olo 10mcg / Olo 5mcg Patients were administered placebo in the first period, Olodaterol 10 mcg qd in the second period and Olodaterol 5 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg / Placebo / Olo 10mcg Patients were administered Olodaterol 5 mcg qd in the first period, placebo in the second period and Olodaterol 10 mcg qd in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg / Olo 10mcg / Placebo Patients were administered Olodaterol 5 mcg qd in the first period, Olodaterol 10 mcg qd in the second period and placebo in the third period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg / Olo 5mcg / Placebo Patients were administered Olodaterol 10 mcg qd in the first period, Olodaterol 5 mcg qd in the second period and placebo in the third period. Olodaterol was administered via the Respimat inhaler.
Overall Study Adverse Event	1	1	0	5	3
Overall Study Protocol Violation	0	0	2	0	0
Overall Study Withdrawal by Subject	0	2	0	0	1
Overall Study Other reasons not listed above	2	0	0	0	0

Baseline Characteristics

Effect of Treatment BI 1744 CL (5 and 10 mcg) Versus Placebo on Exercise Endurance Time During Constant Work Rate Cycle Ergometry I

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Total n=151 Participants Total number of patients treated in the study. This was a randomised, double-blind, placebo-controlled, 3-way crossover trial. 151 patients were assigned randomly to one of 3 treatment sequences in which they received each of 3 treatments. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.
Age, Continuous	60.6 years STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint.

Primary endpoint was endurance time during constant work rate ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. Mixed effects model on log10 transformation data. Adjusted means are back transformed to report as geometric means. Standard errors (SEs) are calculated using the delta method.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=136 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Endurance Time After 6 Weeks	369.81 seconds Standard Error 11.941	421.58 seconds Standard Error 13.459	420.72 seconds Standard Error 13.602

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=135 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks	1.917 liters Standard Error 0.038	2.099 liters Standard Error 0.038	2.091 liters Standard Error 0.038

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint.

Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods. Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=136 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks	5.870 Scores on a scale Standard Error 0.185	5.104 Scores on a scale Standard Error 0.182	5.235 Scores on a scale Standard Error 0.185

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=134 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=139 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=133 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks	2.220 liters Standard Error 0.032	2.478 liters Standard Error 0.032	2.513 liters Standard Error 0.032

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=135 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks	1.887 liters Standard Error 0.035	2.067 liters Standard Error 0.035	2.024 liters Standard Error 0.035

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=135 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks	0.288 Scores on a scale Standard Error 0.041	0.185 Scores on a scale Standard Error 0.040	0.224 Scores on a scale Standard Error 0.041

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint.

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=136 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks	6.978 Scores on a scale Standard Error 0.143	6.890 Scores on a scale Standard Error 0.141	7.234 Scores on a scale Standard Error 0.143

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=134 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=139 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=134 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks	4.977 liters Standard Error 0.062	4.855 liters Standard Error 0.061	4.862 liters Standard Error 0.062

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=134 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=139 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=134 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks	4.950 liters Standard Error 0.064	4.740 liters Standard Error 0.063	4.577 liters Standard Error 0.064

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Measured using body plethysmography

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=134 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks	2.170 liters Standard Error 0.040	2.289 liters Standard Error 0.040	2.262 liters Standard Error 0.040

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Measured using body plethysmography

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=134 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks	2.221 liters Standard Error 0.040	2.427 liters Standard Error 0.040	2.437 liters Standard Error 0.040

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Measured using body plethysmography

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=134 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks	7.142 liters Standard Error 0.064	7.148 liters Standard Error 0.063	7.121 liters Standard Error 0.064

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=140 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=134 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks	7.156 liters Standard Error 0.066	7.142 liters Standard Error 0.066	6.997 liters Standard Error 0.067

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=137 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=137 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks	1.475 liters Standard Error 0.017	1.564 liters Standard Error 0.017	1.576 liters Standard Error 0.017

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=137 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=137 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks	1.473 liters Standard Error 0.019	1.698 liters Standard Error 0.019	1.699 liters Standard Error 0.019

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=136 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=136 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks	3.212 liters Standard Error 0.037	3.319 liters Standard Error 0.037	3.310 liters Standard Error 0.037

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=136 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=136 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks	3.187 liters Standard Error 0.034	3.471 liters Standard Error 0.034	3.477 liters Standard Error 0.034

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=136 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=137 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=137 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks	4.374 liters/second Standard Error 0.059	4.692 liters/second Standard Error 0.059	4.677 liters/second Standard Error 0.059

SECONDARY outcome

Timeframe: 6 weeks

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.