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 II (NCT NCT01040793)

NCT ID: NCT01040793

Last Updated: 2014-07-08

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: 157 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

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	26	26	26	26	26	27
Overall Study COMPLETED	20	21	23	22	22	26
Overall Study NOT COMPLETED	6	5	3	4	4	1

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 / 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 Adverse Event	5	3	0	2	2	1
Overall Study Protocol Violation	1	1	1	0	1	0
Overall Study Lost to Follow-up	0	1	1	0	0	0
Overall Study Withdrawal by Subject	0	0	0	2	0	0
Overall Study Other reasons not listed above	0	0	1	0	1	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 II

Baseline characteristics by cohort

Measure	Overall Study n=157 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	41 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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Endurance Time After 6 Weeks	354.33 seconds Standard Error 12.069	396.31 seconds Standard Error 13.680	391.45 seconds Standard Error 13.566

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks	2.162 liters Standard Error 0.039	2.246 liters Standard Error 0.039	2.328 liters Standard Error 0.039

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks	5.585 Scores on a scale Standard Error 0.177	5.250 Scores on a scale Standard Error 0.180	5.520 Scores on a scale Standard Error 0.181

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=138 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks	2.273 liters Standard Error 0.036	2.437 liters Standard Error 0.036	2.468 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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks	2.158 liters Standard Error 0.039	2.236 liters Standard Error 0.040	2.330 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.

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks	0.389 Scores on a scale Standard Error 0.062	0.315 Scores on a scale Standard Error 0.063	0.364 Scores on a scale 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.

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=141 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks	7.010 Scores on a scale Standard Error 0.129	7.101 Scores on a scale Standard Error 0.131	7.351 Scores on a scale Standard Error 0.132

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

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=145 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=141 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks	4.842 liters Standard Error 0.062	4.757 liters Standard Error 0.063	4.723 liters Standard Error 0.063

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

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=145 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=141 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks	4.770 liters Standard Error 0.065	4.557 liters Standard Error 0.065	4.583 liters Standard Error 0.065

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

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=146 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=142 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks	2.463 liters Standard Error 0.041	2.613 liters Standard Error 0.041	2.618 liters Standard Error 0.042

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

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=146 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=142 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks	2.493 liters Standard Error 0.040	2.725 liters Standard Error 0.040	2.696 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

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=146 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=142 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks	7.311 liters Standard Error 0.067	7.368 liters Standard Error 0.067	7.340 liters Standard Error 0.068

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

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=146 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=142 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks	7.262 liters Standard Error 0.069	7.285 liters Standard Error 0.069	7.272 liters Standard Error 0.069

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 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	1.520 liters Standard Error 0.024	1.630 liters Standard Error 0.025	1.630 liters Standard Error 0.025

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 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	1.577 liters Standard Error 0.026	1.768 liters Standard Error 0.026	1.771 liters Standard Error 0.026

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks	3.103 liters Standard Error 0.039	3.222 liters Standard Error 0.040	3.222 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.

Outcome measures

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks	3.144 liters Standard Error 0.039	3.409 liters Standard Error 0.040	3.425 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.

Outcome measures

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks	4.258 liters/second Standard Error 0.081	4.539 liters/second Standard Error 0.081	4.549 liters/second Standard Error 0.082

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

Measure	Placebo n=146 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks	4.324 liters/second Standard Error 0.085	4.904 liters/second Standard Error 0.085	4.876 liters/second Standard Error 0.086

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Treated set. Statistics only include patients with both a baseline and a post dose value.

Change from Baseline to Day 43 in Blood Pressure with spirometry. Baseline is defined as mean of pre-treatment values at a given time point.

Outcome measures

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=144 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Change From Baseline to Day 43 in Blood Pressure Systolic blood pressure	-0.5 mmHg Standard Deviation 15.87	-1.5 mmHg Standard Deviation 15.47	-1.4 mmHg Standard Deviation 15.31
Change From Baseline to Day 43 in Blood Pressure Diastolic blood pressure	-0.8 mmHg Standard Deviation 8.95	-1.8 mmHg Standard Deviation 8.35	-2.2 mmHg Standard Deviation 9.5

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Treated set. Statistics only include patients with both a baseline and a post dose value.

Change from Baseline to Day 43 in Pulse rate with spirometry. Baseline is defined as mean of pre-treatment values at a given time point.

Outcome measures

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=144 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=139 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Change From Baseline to Day 43 in Pulse Rate	-2.3 beats/min Standard Deviation 12.33	-1.8 beats/min Standard Deviation 11.69	-1.6 beats/min Standard Deviation 10.36

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Treated set.

Number of Patients with notable changes in heart rate (HR). Notable HR increase defined as >=25% increase and on-treatment HR > 100 bpm; Notable HR decrease defined as >=25% decrease and on-treatment HR < 50 bpm.

Outcome measures

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Number of Patients With Notable Changes in Heart Rate 30 min pre-dose: no notable change	98.6 percentage of participants	97.9 percentage of participants	97.1 percentage of participants
Number of Patients With Notable Changes in Heart Rate 40 min post-dose: increase (N=147,142,140)	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Number of Patients With Notable Changes in Heart Rate 40 min post-dose: no notable change(N=147,142,140)	99.3 percentage of participants	95.8 percentage of participants	96.4 percentage of participants
Number of Patients With Notable Changes in Heart Rate 30 min pre-dose: increase	0.7 percentage of participants	0.7 percentage of participants	0.0 percentage of participants
Number of Patients With Notable Changes in Heart Rate 30 min pre-dose: decrease	0.7 percentage of participants	1.4 percentage of participants	2.9 percentage of participants
Number of Patients With Notable Changes in Heart Rate 40 min post-dose: decrease (N=147,142,140)	0.7 percentage of participants	4.2 percentage of participants	3.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Treated set.

Number of Patients with notable increase in PR intervals. Notable PR interval increase defined as >=25% increase and on-treatment PR interval > 200 ms.

Outcome measures

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Number of Patients With Notable Increase in PR Intervals 30 min pre-dose: increase	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Number of Patients With Notable Increase in PR Intervals 30 min pre-dose: no increase	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Number of Patients With Notable Increase in PR Intervals 40 min post-dose: no increase (N=147, 142, 140)	99.3 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Number of Patients With Notable Increase in PR Intervals 40 min post-dose: increase (N=147, 142, 140)	0.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Treated set.

Number of Patients with notable increase in QRS intervals. Notable QRS interval increase defined as >=10% increase and on-treatment QRS interval > 110 ms.

Outcome measures

Measure	Placebo n=147 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=143 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 10 mcg qd n=140 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Number of Patients With Notable Increase in QRS Intervals 30 min pre-dose: increase	0.7 percentage of participants	0.7 percentage of participants	0.7 percentage of participants
Number of Patients With Notable Increase in QRS Intervals 40 min post-dose: no increase (N=147, 142, 140)	98.6 percentage of participants	99.3 percentage of participants	99.3 percentage of participants
Number of Patients With Notable Increase in QRS Intervals 30 min pre-dose: no increase	99.3 percentage of participants	99.3 percentage of participants	99.3 percentage of participants
Number of Patients With Notable Increase in QRS Intervals 40 min post-dose: increase (N=147, 142, 140)	1.4 percentage of participants	0.7 percentage of participants	0.7 percentage of participants

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Olo 5 mcg

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Olo 10 mcg

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=149 participants at risk Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.	Olo 5 mcg n=150 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=147 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Cardiac disorders Atrial fibrillation	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Gastrointestinal disorders Mallory-Weiss syndrome	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
General disorders Death	0.00% 0/149 • 6 weeks	0.00% 0/150 • 6 weeks	0.68% 1/147 • 6 weeks
Infections and infestations Erysipelas	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Infections and infestations Pyelonephritis	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Injury, poisoning and procedural complications Joint injury	0.00% 0/149 • 6 weeks	0.00% 0/150 • 6 weeks	0.68% 1/147 • 6 weeks
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/149 • 6 weeks	0.00% 0/150 • 6 weeks	0.68% 1/147 • 6 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.67% 1/149 • 6 weeks	0.00% 0/150 • 6 weeks	0.00% 0/147 • 6 weeks
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Nervous system disorders Cerebrovascular accident	0.00% 0/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.67% 1/149 • 6 weeks	0.67% 1/150 • 6 weeks	0.00% 0/147 • 6 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/149 • 6 weeks	0.00% 0/150 • 6 weeks	0.68% 1/147 • 6 weeks
Respiratory, thoracic and mediastinal disorders Foreign body aspiration	0.67% 1/149 • 6 weeks	0.00% 0/150 • 6 weeks	0.00% 0/147 • 6 weeks

Other adverse events

Measure	Placebo n=149 participants at risk Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.	Olo 5 mcg n=150 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=147 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	6.0% 9/149 • 6 weeks	5.3% 8/150 • 6 weeks	2.7% 4/147 • 6 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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
• Publication restrictions are in place

Restriction type: OTHER