Trial Outcomes & Findings for A Study to Compare the Efficacy and Safety of Different Dosings of Olodaterol Administered With the Respimat® Inhaler in Patients With Moderate to Severe Asthma (NCT NCT01311661)

NCT ID: NCT01311661

Last Updated: 2014-05-01

Results Overview

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 206 participants
• Primary outcome timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks
• Results posted on: 2014-05-01

Participant Flow

Participant milestones

Measure	Study Total This was a double-blind, 3-period crossover trial. 206 patients were assigned randomly to one of 12 treatment sequences with either 5 microgram (mcg) Olodaterol (Olo) once daily (qd) and 2.5 mcg Olodaterol twice daily (bid) and placebo (6 sequences) or 10 mcg Olodaterol qd and 5 mcg Olodaterol bid and placebo (6 sequences). The duration of each treatment period was 3 weeks separated by washout periods of 2 weeks.
Overall Study STARTED	206
Overall Study Received Placebo	201
Overall Study Received Olo 2.5 mcg Bid	101
Overall Study Received Olo 5 mcg qd	101
Overall Study Received Olo 5 mcg Bid	101
Overall Study Received Olo 10 mcg qd	102
Overall Study COMPLETED	199
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Study Total This was a double-blind, 3-period crossover trial. 206 patients were assigned randomly to one of 12 treatment sequences with either 5 microgram (mcg) Olodaterol (Olo) once daily (qd) and 2.5 mcg Olodaterol twice daily (bid) and placebo (6 sequences) or 10 mcg Olodaterol qd and 5 mcg Olodaterol bid and placebo (6 sequences). The duration of each treatment period was 3 weeks separated by washout periods of 2 weeks.
Overall Study Adverse Event	2
Overall Study Protocol Violation	3
Overall Study Withdrawal by Subject	2

Baseline Characteristics

A Study to Compare the Efficacy and Safety of Different Dosings of Olodaterol Administered With the Respimat® Inhaler in Patients With Moderate to Severe Asthma

Baseline characteristics by cohort

Measure	Study Total n=206 Participants This was a double-blind, 3-period crossover trial. 206 patients were assigned randomly to one of 12 treatment sequences with either 5 microgram (mcg) Olodaterol (Olo) once daily (qd) and 2.5 mcg Olodaterol twice daily (bid) and placebo (6 sequences) or 10 mcg Olodaterol qd and 5 mcg Olodaterol bid and placebo (6 sequences). The duration of each treatment period was 3 weeks separated by washout periods of 2 weeks.
Age, Continuous	43.7 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	109 Participants n=5 Participants
Sex: Female, Male Male	97 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: Full analysis set (FAS). FAS is defined as all patients in the treated set for whom the baseline (pre-dose) value is available, and who have a value for the primary endpoint for at least one crossover period.

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.

Outcome measures

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period	0.022 Liter Standard Error 0.020	0.213 Liter Standard Error 0.024	0.173 Liter Standard Error 0.024	0.250 Liter Standard Error 0.024	0.231 Liter Standard Error 0.024

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Outcome measures

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period	0.052 Liter Standard Error 0.020	0.242 Liter Standard Error 0.024	0.212 Liter Standard Error 0.024	0.266 Liter Standard Error 0.024	0.272 Liter Standard Error 0.024

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period	-0.010 Liter Standard Error 0.020	0.186 Liter Standard Error 0.025	0.135 Liter Standard Error 0.025	0.233 Liter Standard Error 0.025	0.189 Liter Standard Error 0.025

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak FEV1 within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Peak FEV1 Within 24 Hours Post-dose Response	0.227 Liter Standard Error 0.021	0.410 Liter Standard Error 0.027	0.380 Liter Standard Error 0.027	0.449 Liter Standard Error 0.027	0.437 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Trough FEV1 Response	0.033 Liter Standard Error 0.022	0.189 Liter Standard Error 0.027	0.134 Liter Standard Error 0.027	0.229 Liter Standard Error 0.027	0.205 Liter Standard Error 0.027

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response	-0.004 Liter Standard Error 0.022	0.132 Liter Standard Error 0.027	0.119 Liter Standard Error 0.027	0.138 Liter Standard Error 0.026	0.143 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response	-0.056 Liter Standard Error 0.023	0.102 Liter Standard Error 0.028	0.081 Liter Standard Error 0.028	0.114 Liter Standard Error 0.028	0.079 Liter Standard Error 0.028

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response	-0.029 Liter Standard Error 0.021	0.116 Liter Standard Error 0.026	0.099 Liter Standard Error 0.026	0.127 Liter Standard Error 0.026	0.111 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post-dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Peak FVC Within 24 Hours Post-dose Response	0.246 Liter Standard Error 0.024	0.382 Liter Standard Error 0.030	0.371 Liter Standard Error 0.030	0.390 Liter Standard Error 0.030	0.373 Liter Standard Error 0.029

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Trough FVC Response	-0.013 Liter Standard Error 0.024	0.096 Liter Standard Error 0.031	0.079 Liter Standard Error 0.031	0.105 Liter Standard Error 0.031	0.098 Liter Standard Error 0.031

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.

Outcome measures

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response	0.101 Liter/sec Standard Error 0.060	0.730 Liter/sec Standard Error 0.075	0.703 Liter/sec Standard Error 0.075	0.732 Liter/sec Standard Error 0.074	0.787 Liter/sec Standard Error 0.074

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response	-0.135 Liter/sec Standard Error 0.061	0.530 Liter/sec Standard Error 0.077	0.430 Liter/sec Standard Error 0.076	0.567 Liter/sec Standard Error 0.076	0.464 Liter/sec Standard Error 0.076

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.

Outcome measures

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response	-0.014 Liter/sec Standard Error 0.059	0.627 Liter/sec Standard Error 0.073	0.563 Liter/sec Standard Error 0.073	0.653 Liter/sec Standard Error 0.073	0.629 Liter/sec Standard Error 0.073

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post dose measured following the morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Peak PEF Within 24 Hours Post-dose Response	0.663 Liter/sec Standard Error 0.068	1.254 Liter/sec Standard Error 0.087	1.185 Liter/sec Standard Error 0.087	1.257 Liter/sec Standard Error 0.086	1.286 Liter/sec Standard Error 0.086

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks

Population: FAS

Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=99 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=100 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Trough PEF Response	-0.009 Liter/sec Standard Error 0.062	0.520 Liter/sec Standard Error 0.078	0.401 Liter/sec Standard Error 0.078	0.594 Liter/sec Standard Error 0.077	0.472 Liter/sec Standard Error 0.077

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

PEF a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Mean Pre-dose Morning PEF (PEF a.m.)	395.36 Liter/min Standard Error 2.857	428.32 Liter/min Standard Error 3.586	427.99 Liter/min Standard Error 3.575	427.02 Liter/min Standard Error 3.562	424.26 Liter/min Standard Error 3.562

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

PEF p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Mean Pre-dose Evening PEF (PEF p.m.)	409.93 Liter/min Standard Error 2.717	438.80 Liter/min Standard Error 3.418	441.98 Liter/min Standard Error 3.407	441.74 Liter/min Standard Error 3.395	443.25 Liter/min Standard Error 3.395

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
PEF Daily Variability	10.157 Percentage Standard Error 0.288	8.576 Percentage Standard Error 0.371	8.732 Percentage Standard Error 0.369	8.419 Percentage Standard Error 0.368	9.468 Percentage Standard Error 0.368

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

FEV1 a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Mean Pre-dose Morning FEV1 (FEV1 a.m.)	2425.1 mL Standard Error 17.870	2598.5 mL Standard Error 22.276	2580.2 mL Standard Error 22.208	2574.3 mL Standard Error 22.133	2575.5 mL Standard Error 22.133

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

FEV1 p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Mean Pre-dose Evening FEV1 (FEV1 p.m.)	2474.3 mL Standard Error 17.692	2616.6 mL Standard Error 21.949	2606.5 mL Standard Error 21.884	2616.5 mL Standard Error 21.810	2631.7 mL Standard Error 21.809

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Mean Number of Puffs of Rescue Medication During the Whole Day	1.665 Puffs Standard Error 0.091	1.110 Puffs Standard Error 0.120	1.028 Puffs Standard Error 0.119	1.077 Puffs Standard Error 0.119	1.119 Puffs Standard Error 0.119

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

Percentage of asthma-symptom free days of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM3 device.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Percentage of Asthma Symptom Free Days	23.630 Percentage of asthma symptom free days Standard Error 2.235	33.929 Percentage of asthma symptom free days Standard Error 3.554	36.306 Percentage of asthma symptom free days Standard Error 3.644	28.844 Percentage of asthma symptom free days Standard Error 3.271	28.049 Percentage of asthma symptom free days Standard Error 3.368

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

Assessed by patients at home using the AM3 device during each period of randomised treatment.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) Did not wake up	93 Number of patients	50 Number of patients	53 Number of patients	44 Number of patients	47 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) Woke up once	67 Number of patients	31 Number of patients	36 Number of patients	41 Number of patients	32 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) Woke up 2-5 times	36 Number of patients	18 Number of patients	10 Number of patients	14 Number of patients	19 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) Woke up > 5 times	5 Number of patients	0 Number of patients	1 Number of patients	0 Number of patients	2 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) Was awake all night	0 Number of patients	0 Number of patients	0 Number of patients	2 Number of patients	1 Number of patients

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

Assessed by patients at home using the AM3 device during each period of randomised treatment .

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) No asthma symptoms	31 Number of patients	24 Number of patients	27 Number of patients	18 Number of patients	20 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) Mild asthma symptoms	66 Number of patients	45 Number of patients	42 Number of patients	42 Number of patients	41 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) Moderate asthma symptoms	85 Number of patients	25 Number of patients	27 Number of patients	36 Number of patients	37 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) Severe asthma symptoms	18 Number of patients	4 Number of patients	3 Number of patients	4 Number of patients	2 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) Very severe asthma symptoms	1 Number of patients	1 Number of patients	1 Number of patients	1 Number of patients	1 Number of patients

SECONDARY outcome

Timeframe: 0-3 weeks

Population: FAS

Assessed by patients at home using the AM3 device during each period of randomised treatment.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) No asthma symptoms	39 Number of patients	32 Number of patients	29 Number of patients	21 Number of patients	21 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) Mild asthma symptoms	76 Number of patients	35 Number of patients	38 Number of patients	48 Number of patients	40 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) Moderate asthma symptoms	74 Number of patients	26 Number of patients	32 Number of patients	29 Number of patients	35 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) Severe asthma symptoms	9 Number of patients	4 Number of patients	1 Number of patients	2 Number of patients	3 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) Very severe asthma symptoms	3 Number of patients	2 Number of patients	0 Number of patients	1 Number of patients	2 Number of patients

SECONDARY outcome

Timeframe: 3 weeks

Population: FAS

Control of asthma as assessed by the ACQ at the end of each 3-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=99 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=100 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=101 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Total Asthma Control Questionnaire (ACQ) Score	1.613 Units on a scale Standard Error 0.040	1.256 Units on a scale Standard Error 0.053	1.317 Units on a scale Standard Error 0.053	1.312 Units on a scale Standard Error 0.053	1.311 Units on a scale Standard Error 0.053

SECONDARY outcome

Timeframe: 3 weeks + 12 days

Population: Treated set

Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.

Outcome measures

Measure	Placebo n=201 Participants Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=101 Participants Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=101 Participants Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=102 Participants Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Atrioventricular block first degree	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Sinus tachycardia	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Aspartate aminotransferase increased	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Blood creatinine increased	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Blood glucose increased	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Blood urea abnormal	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Gamma-glutamyltransferase increased	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Blood creatine phosphokinase increased	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Blood urine present	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Anaemia	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Hypertension	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Olo 2.5 mcg Bid

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Olo 5 mcg qd

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Olo 5 mcg Bid

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Olo 10 mcg qd

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=201 participants at risk Matching Placebo delivered by the Respimat Inhaler. Two actuations bid (morning and evening dosing).	Olo 2.5 mcg Bid n=101 participants at risk Olodaterol 2.5 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=101 participants at risk Olodaterol 5 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=101 participants at risk Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=102 participants at risk Olodaterol 10 mcg qd (morning) and matching Placebo in the evening delivered by the Respimat Inhaler.
Infections and infestations Gastroenteritis	0.00% 0/201 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.99% 1/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/102 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Infections and infestations Diverticulitis	0.50% 1/201 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/102 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Injury, poisoning and procedural complications Concussion	0.00% 0/201 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.99% 1/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/102 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Injury, poisoning and procedural complications Fall	0.00% 0/201 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.99% 1/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/102 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Injury, poisoning and procedural complications Laceration	0.00% 0/201 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.99% 1/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/102 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Injury, poisoning and procedural complications Meniscus lesion	0.50% 1/201 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/101 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.	0.00% 0/102 • 3 weeks treatment period + 12 days Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.

Other adverse events

Adverse event data not reported

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