Trial Outcomes & Findings for A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma. (NCT NCT01013753)

NCT ID: NCT01013753

Last Updated: 2014-06-27

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

198 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, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks

Results posted on

2014-06-27

Participant Flow

Participant milestones

Participant milestones
Measure
Study Total
This was a randomised, double-blind, double dummy, placebo- and active-controlled, 6 treatment, 4 period incomplete crossover trial. 198 patients were assigned randomly to one of 30 treatment sequences, each sequence comprising 4 out of the 6 treatments listed: one of four doses (20 microgram (mcg), 10 mcg, 5 mcg or 2 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo. The duration of each treatment period was 4 weeks with no washout periods between treatments.
Overall Study
STARTED
198
Overall Study
Received Placebo
125
Overall Study
Received Olo 2 mcg qd
121
Overall Study
Received Olo 5 mcg qd
130
Overall Study
Received Olo 10 mcg qd
127
Overall Study
Received Olo 20 mcg qd
124
Overall Study
Received Form 12 mcg Bid
125
Overall Study
COMPLETED
182
Overall Study
NOT COMPLETED
16

Reasons for withdrawal

Reasons for withdrawal
Measure
Study Total
This was a randomised, double-blind, double dummy, placebo- and active-controlled, 6 treatment, 4 period incomplete crossover trial. 198 patients were assigned randomly to one of 30 treatment sequences, each sequence comprising 4 out of the 6 treatments listed: one of four doses (20 microgram (mcg), 10 mcg, 5 mcg or 2 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo. The duration of each treatment period was 4 weeks with no washout periods between treatments.
Overall Study
Adverse Event
8
Overall Study
Protocol Violation
3
Overall Study
Lost to Follow-up
1
Overall Study
Withdrawal by Subject
2
Overall Study
Other
2

Baseline Characteristics

A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Study Total
n=198 Participants
This was a randomised, double-blind, double dummy, placebo- and active-controlled, 6 treatment, 4 period incomplete crossover trial. 198 patients were assigned randomly to one of 30 treatment sequences, each sequence comprising 4 out of the 6 treatments listed: one of four doses (20 microgram (mcg), 10 mcg, 5 mcg or 2 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo. The duration of each treatment period was 4 weeks with no washout periods between treatments.
Age, Continuous
45.0 years
STANDARD_DEVIATION 11.8 • n=99 Participants
Sex: Female, Male
Female
112 Participants
n=99 Participants
Sex: Female, Male
Male
86 Participants
n=99 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, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer 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
-0.004 Liter
Standard Error 0.025
0.135 Liter
Standard Error 0.025
0.178 Liter
Standard Error 0.025
0.201 Liter
Standard Error 0.025
0.225 Liter
Standard Error 0.025
0.164 Liter
Standard Error 0.025

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, 11 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period
-0.039 Liter
Standard Error 0.026
0.124 Liter
Standard Error 0.026
0.173 Liter
Standard Error 0.026
0.194 Liter
Standard Error 0.026
0.211 Liter
Standard Error 0.026
0.145 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, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period
0.031 Liter
Standard Error 0.026
0.147 Liter
Standard Error 0.026
0.183 Liter
Standard Error 0.025
0.208 Liter
Standard Error 0.026
0.238 Liter
Standard Error 0.026
0.183 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, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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 evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak FEV1 Within 24 Hours Post-dose Response
0.224 Liter
Standard Error 0.026
0.326 Liter
Standard Error 0.027
0.359 Liter
Standard Error 0.026
0.385 Liter
Standard Error 0.027
0.404 Liter
Standard Error 0.027
0.390 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 evening dose after 4 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 the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Trough FEV1 Response
0.013 Liter
Standard Error 0.026
0.116 Liter
Standard Error 0.026
0.146 Liter
Standard Error 0.026
0.182 Liter
Standard Error 0.026
0.211 Liter
Standard Error 0.026
0.115 Liter
Standard Error 0.026

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, 11 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
-0.047 Liter
Standard Error 0.029
0.056 Liter
Standard Error 0.029
0.109 Liter
Standard Error 0.029
0.094 Liter
Standard Error 0.029
0.122 Liter
Standard Error 0.029
0.055 Liter
Standard Error 0.029

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, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
-0.005 Liter
Standard Error 0.029
0.055 Liter
Standard Error 0.029
0.109 Liter
Standard Error 0.028
0.110 Liter
Standard Error 0.029
0.139 Liter
Standard Error 0.029
0.085 Liter
Standard Error 0.029

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 min, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
-0.026 Liter
Standard Error 0.028
0.056 Liter
Standard Error 0.028
0.109 Liter
Standard Error 0.028
0.102 Liter
Standard Error 0.028
0.131 Liter
Standard Error 0.028
0.070 Liter
Standard Error 0.028

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, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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 trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak FVC Within 24 Hours Post-dose Response
0.253 Liter
Standard Error 0.031
0.300 Liter
Standard Error 0.031
0.356 Liter
Standard Error 0.031
0.342 Liter
Standard Error 0.031
0.380 Liter
Standard Error 0.031
0.326 Liter
Standard Error 0.031

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 evening dose after 4 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 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Trough FVC Response
-0.022 Liter
Standard Error 0.029
0.015 Liter
Standard Error 0.029
0.069 Liter
Standard Error 0.029
0.088 Liter
Standard Error 0.029
0.107 Liter
Standard Error 0.029
0.029 Liter
Standard Error 0.029

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, 11 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response
-0.117 Liter/sec
Standard Error 0.076
0.291 Liter/sec
Standard Error 0.077
0.449 Liter/sec
Standard Error 0.076
0.495 Liter/sec
Standard Error 0.077
0.553 Liter/sec
Standard Error 0.077
0.471 Liter/sec
Standard Error 0.076

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, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response
0.043 Liter/sec
Standard Error 0.075
0.380 Liter/sec
Standard Error 0.075
0.528 Liter/sec
Standard Error 0.075
0.575 Liter/sec
Standard Error 0.075
0.692 Liter/sec
Standard Error 0.075
0.594 Liter/sec
Standard Error 0.075

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response
-0.038 Liter/sec
Standard Error 0.074
0.336 Liter/sec
Standard Error 0.074
0.489 Liter/sec
Standard Error 0.074
0.534 Liter/sec
Standard Error 0.074
0.623 Liter/sec
Standard Error 0.074
0.532 Liter/sec
Standard Error 0.074

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, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 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 evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak PEF Within 24 Hours Post-dose Response
0.664 Liter/sec
Standard Error 0.079
0.966 Liter/sec
Standard Error 0.079
1.093 Liter/sec
Standard Error 0.078
1.130 Liter/sec
Standard Error 0.079
1.198 Liter/sec
Standard Error 0.079
1.168 Liter/sec
Standard Error 0.079

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 evening dose after 4 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 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Trough PEF Response
0.031 Liter/sec
Standard Error 0.078
0.295 Liter/sec
Standard Error 0.078
0.499 Liter/sec
Standard Error 0.077
0.515 Liter/sec
Standard Error 0.078
0.655 Liter/sec
Standard Error 0.078
0.478 Liter/sec
Standard Error 0.078

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

PEF a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Mean Pre-dose Morning PEF (PEF a.m.)
361.89 Liter/min
Standard Error 4.548
383.90 Liter/min
Standard Error 4.567
390.91 Liter/min
Standard Error 4.519
389.78 Liter/min
Standard Error 4.539
394.82 Liter/min
Standard Error 4.560
385.42 Liter/min
Standard Error 4.539

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

PEF p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Mean Pre-dose Evening PEF (PEF p.m.)
379.44 Liter/min
Standard Error 4.398
394.36 Liter/min
Standard Error 4.418
404.28 Liter/min
Standard Error 4.368
403.06 Liter/min
Standard Error 4.389
407.89 Liter/min
Standard Error 4.410
399.88 Liter/min
Standard Error 4.389

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

PEF daily variability was assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks 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

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=122 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
PEF Daily Variability
11.688 Percentage
Standard Error 0.480
9.694 Percentage
Standard Error 0.484
9.593 Percentage
Standard Error 0.475
9.851 Percentage
Standard Error 0.480
9.899 Percentage
Standard Error 0.483
10.417 Percentage
Standard Error 0.479

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

FEV1 a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Mean Pre-dose Morning FEV1 (FEV1 a.m.)
2.309 L
Standard Error 0.028
2.402 L
Standard Error 0.028
2.438 L
Standard Error 0.028
2.445 L
Standard Error 0.028
2.479 L
Standard Error 0.028
2.403 L
Standard Error 0.028

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

FEV1 p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Mean Pre-dose Evening FEV1 (FEV1 p.m.)
2.378 L
Standard Error 0.027
2.428 L
Standard Error 0.027
2.460 L
Standard Error 0.027
2.467 L
Standard Error 0.027
2.495 L
Standard Error 0.027
2.457 L
Standard Error 0.027

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Mean Number of Puffs of Rescue Medication During the Whole Day
1.749 Number of Puffs
Standard Error 0.130
1.222 Number of Puffs
Standard Error 0.130
1.317 Number of Puffs
Standard Error 0.128
1.271 Number of Puffs
Standard Error 0.129
1.092 Number of Puffs
Standard Error 0.130
1.300 Number of Puffs
Standard Error 0.129

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Percentage of asthma-symptom free days after the first 2 weeks 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 AM2+ device.

Outcome measures

Outcome measures
Measure
Placebo
n=123 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Percentage of Asthma Symptom Free Days
18.502 Percentage of asthma symptom free days
Standard Error 2.494
26.430 Percentage of asthma symptom free days
Standard Error 2.973
22.348 Percentage of asthma symptom free days
Standard Error 2.835
23.624 Percentage of asthma symptom free days
Standard Error 2.951
21.326 Percentage of asthma symptom free days
Standard Error 2.803
23.664 Percentage of asthma symptom free days
Standard Error 2.797

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Did not wake up
55 Number of patients
60 Number of patients
58 Number of patients
56 Number of patients
63 Number of patients
59 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Woke up once
37 Number of patients
36 Number of patients
34 Number of patients
34 Number of patients
34 Number of patients
29 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Woke up 2-5 times
26 Number of patients
17 Number of patients
30 Number of patients
30 Number of patients
20 Number of patients
33 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Woke up > 5 times
3 Number of patients
5 Number of patients
2 Number of patients
1 Number of patients
2 Number of patients
2 Number of patients
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
Was awake all night
1 Number of patients
1 Number of patients
2 Number of patients
2 Number of patients
1 Number of patients
0 Number of patients

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
No asthma symptoms
20 Number of patients
26 Number of patients
29 Number of patients
23 Number of patients
21 Number of patients
24 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
Mild asthma symptoms
31 Number of patients
46 Number of patients
29 Number of patients
37 Number of patients
38 Number of patients
37 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
Moderate asthma symptoms
56 Number of patients
37 Number of patients
51 Number of patients
52 Number of patients
54 Number of patients
49 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
Severe asthma symptoms
15 Number of patients
10 Number of patients
12 Number of patients
10 Number of patients
6 Number of patients
12 Number of patients
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
Very severe asthma symptoms
0 Number of patients
0 Number of patients
5 Number of patients
1 Number of patients
1 Number of patients
1 Number of patients

SECONDARY outcome

Timeframe: 2-4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=123 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=120 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=123 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
No asthma symptoms
27 Number of patients
31 Number of patients
22 Number of patients
25 Number of patients
27 Number of patients
26 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
Mild asthma symptoms
32 Number of patients
47 Number of patients
48 Number of patients
40 Number of patients
45 Number of patients
39 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
Moderate asthma symptoms
49 Number of patients
29 Number of patients
45 Number of patients
46 Number of patients
43 Number of patients
46 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
Severe asthma symptoms
14 Number of patients
10 Number of patients
11 Number of patients
10 Number of patients
5 Number of patients
10 Number of patients
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
Very severe asthma symptoms
0 Number of patients
2 Number of patients
0 Number of patients
2 Number of patients
0 Number of patients
2 Number of patients

SECONDARY outcome

Timeframe: 4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Total score from the Standardised Asthma Quality of Life Questionnaire (AQLQ (s)) at the end of each 4 week treatment period. The AQLQ(s) contains 32 questions, each question has a 7 point scale from 1 (highest intensity) till 7 (no symptoms). Total score was defined as the sum of all items divided by the number of items.

Outcome measures

Outcome measures
Measure
Placebo
n=122 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=125 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=121 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=118 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Total Asthma Quality of Life Questionnaire (AQLQ(s)) Score
5.174 units on a scale
Standard Error 0.063
5.463 units on a scale
Standard Error 0.064
5.383 units on a scale
Standard Error 0.063
5.437 units on a scale
Standard Error 0.063
5.491 units on a scale
Standard Error 0.064
5.489 units on a scale
Standard Error 0.063

SECONDARY outcome

Timeframe: 4 weeks

Population: FAS including all patients who contributed data for this endpoint.

Control of asthma as assessed by the ACQ at the end of each 4-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

Outcome measures
Measure
Placebo
n=123 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=119 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=126 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=122 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=119 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=122 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Total Asthma Control Questionnaire (ACQ) Score
1.882 units on a scale
Standard Error 0.058
1.561 units on a scale
Standard Error 0.058
1.589 units on a scale
Standard Error 0.057
1.556 units on a scale
Standard Error 0.058
1.488 units on a scale
Standard Error 0.058
1.536 units on a scale
Standard Error 0.058

SECONDARY outcome

Timeframe: 4 weeks

Population: Treated set

Effect on potassium evaluated 1 hour pre-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale.

Outcome measures

Outcome measures
Measure
Placebo
n=119 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=118 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=122 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=117 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=117 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=119 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Potassium 1 Hour Pre-dose
4.067 mmol/L
Interval 4.019 to 4.114
4.051 mmol/L
Interval 4.004 to 4.099
4.051 mmol/L
Interval 4.005 to 4.097
4.061 mmol/L
Interval 4.014 to 4.109
4.057 mmol/L
Interval 4.01 to 4.105
4.080 mmol/L
Interval 4.032 to 4.128

SECONDARY outcome

Timeframe: 4 weeks

Population: Treated set

Effect on potassium evaluated 1 hour post-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale.

Outcome measures

Outcome measures
Measure
Placebo
n=115 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=113 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=118 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=114 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=109 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=114 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Potassium 1 Hour Post-dose
4.097 mmol/L
Interval 4.04 to 4.155
4.069 mmol/L
Interval 4.012 to 4.126
4.013 mmol/L
Interval 3.958 to 4.069
4.004 mmol/L
Interval 3.948 to 4.06
4.015 mmol/L
Interval 3.957 to 4.073
4.059 mmol/L
Interval 4.003 to 4.117

SECONDARY outcome

Timeframe: 4 weeks

Population: Treated set

Effect on potassium evaluated 3 hours post-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale.

Outcome measures

Outcome measures
Measure
Placebo
n=113 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=110 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=119 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=114 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=105 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=114 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Potassium 3 Hours Post-dose
4.029 mmol/L
Interval 3.98 to 4.079
4.026 mmol/L
Interval 3.976 to 4.076
3.997 mmol/L
Interval 3.95 to 4.045
3.979 mmol/L
Interval 3.931 to 4.027
3.992 mmol/L
Interval 3.942 to 4.043
4.007 mmol/L
Interval 3.959 to 4.056

SECONDARY outcome

Timeframe: 4 weeks

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.

Outcome measures

Outcome measures
Measure
Placebo
n=125 Participants
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg qd
n=121 Participants
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg qd
n=130 Participants
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg qd
n=127 Participants
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg qd
n=124 Participants
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg Bid
n=125 Participants
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Atrioventricular block first degree
0 Participants
0 Participants
0 Participants
0 Participants
1 Participants
1 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Blood creatine phosphokinase MB increased
0 Participants
0 Participants
0 Participants
1 Participants
0 Participants
0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Blood creatine phosphokinase increased
0 Participants
0 Participants
0 Participants
1 Participants
0 Participants
0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Blood pressure increased
0 Participants
1 Participants
0 Participants
0 Participants
0 Participants
0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Hypothyroidism
0 Participants
0 Participants
1 Participants
0 Participants
0 Participants
0 Participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Hypertension
0 Participants
0 Participants
1 Participants
1 Participants
1 Participants
0 Participants

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Olo 2 mcg

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Olo 5 mcg

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Olo 10 mcg

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Olo 20 mcg

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Form 12 mcg

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=125 participants at risk
Equivalent Placebo (morning and evening) delivered by the matching Inhaler (Respimat or Aerolizer).
Olo 2 mcg
n=121 participants at risk
Olodaterol 2 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 5 mcg
n=130 participants at risk
Olodaterol 5 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 10 mcg
n=127 participants at risk
Olodaterol 10 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Olo 20 mcg
n=124 participants at risk
Olodaterol 20 mcg qd (evening, equivalent placebo morning) delivered by the Respimat Inhaler.
Form 12 mcg
n=125 participants at risk
Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Infections and infestations
Appendicitis
0.00%
0/125 • 4 weeks
0.00%
0/121 • 4 weeks
0.00%
0/130 • 4 weeks
0.79%
1/127 • 4 weeks
0.00%
0/124 • 4 weeks
0.00%
0/125 • 4 weeks

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

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