Trial Outcomes & Findings for Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients (NCT NCT01533922)
NCT ID: NCT01533922
Last Updated: 2015-09-15
Results Overview
Inspiratory capacity (IC) at rest before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap). Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1. The presented means are adjusted means from the MMRM (Mixed Effects Model Repeated Measures) model.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
295 participants
Primary outcome timeframe
6 weeks
Results posted on
2015-09-15
Participant Flow
This was a randomised, 4-period incomplete block cross-over trial. 295 patients were randomized to one of five treatments sequences and treated. It was a double-blind trial in which each treatment period lasted 6 weeks with a washout period of 21 days between each.
Participant milestones
| Measure |
Tio+Olo 2.5/5 / Tio+Olo 5/5 / Tio / Olo
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
* Tiotropium fixed dose 5 µg
* Olodaterol fixed dose 5 µg
|
Tio+Olo 5/5 / Tio / Olo / Placebo
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
* Tiotropium fixed dose 5 µg
* Olodaterol fixed dose 5 µg
* Oral inhalation of placebo
|
Tio / Olo / Placebo / Tio+Olo 2.5/5
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Tiotropium fixed dose 5 µg
* Olodaterol fixed dose 5 µg
* Oral inhalation of placebo
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
|
Olo / Placebo / Tio+Olo 2.5/5 / Tio+Olo 5/5
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Olodaterol fixed dose 5 µg
* Oral inhalation of placebo
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
|
Placebo / Tio+Olo 2.5/5 / Tio+Olo 5/5 / Tio
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Oral inhalation of placebo
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
* Tiotropium fixed dose 5 µg
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
59
|
59
|
60
|
58
|
59
|
|
Overall Study
Received Placebo
|
0
|
49
|
57
|
57
|
59
|
|
Overall Study
Received Olo 5
|
51
|
52
|
57
|
57
|
0
|
|
Overall Study
Received Tio 5
|
54
|
58
|
59
|
1
|
54
|
|
Overall Study
Received Tio+Olo 2.5/5
|
59
|
0
|
52
|
55
|
56
|
|
Overall Study
Received Tio+Olo 5/5
|
58
|
59
|
0
|
53
|
56
|
|
Overall Study
COMPLETED
|
49
|
47
|
50
|
53
|
53
|
|
Overall Study
NOT COMPLETED
|
10
|
12
|
10
|
5
|
6
|
Reasons for withdrawal
| Measure |
Tio+Olo 2.5/5 / Tio+Olo 5/5 / Tio / Olo
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
* Tiotropium fixed dose 5 µg
* Olodaterol fixed dose 5 µg
|
Tio+Olo 5/5 / Tio / Olo / Placebo
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
* Tiotropium fixed dose 5 µg
* Olodaterol fixed dose 5 µg
* Oral inhalation of placebo
|
Tio / Olo / Placebo / Tio+Olo 2.5/5
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Tiotropium fixed dose 5 µg
* Olodaterol fixed dose 5 µg
* Oral inhalation of placebo
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
|
Olo / Placebo / Tio+Olo 2.5/5 / Tio+Olo 5/5
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Olodaterol fixed dose 5 µg
* Oral inhalation of placebo
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
|
Placebo / Tio+Olo 2.5/5 / Tio+Olo 5/5 / Tio
Patients received a total of four treatments, and each treatment period is separated by a washout period of 21 days. The treatments administered orally via the respimat inhaler, once daily, in the morning were:
* Oral inhalation of placebo
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
* Tiotropium fixed dose 5 µg
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
5
|
8
|
6
|
3
|
4
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
0
|
3
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
1
|
2
|
2
|
1
|
|
Overall Study
Other reason not defined above
|
2
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients
Baseline characteristics by cohort
| Measure |
Overall Study
n=295 Participants
A randomised, double-blind, placebo controlled, 5 treatment, 4-period, incomplete, crossover study. Each treatment period was separated by a washout period of 21 days. The 5 treatments, administered orally via the respimat inhaler, once daily, in the morning were:
* Oral inhalation of placebo
* Olodaterol fixed dose 5 µg
* Tiotropium fixed dose 5 µg
* Fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg
* Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
Treatment sequence is not considered as a factor which may affect the treatment effect due to sufficient washout period added between treatment cycles. As a result, we only display baseline characteristics as a whole population, but not by treatment sequence
|
|---|---|
|
Age, Continuous
|
62.2 years
STANDARD_DEVIATION 7.5 • n=99 Participants
|
|
Sex: Female, Male
Female
|
82 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
213 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Full Analysis Set (FAS) : This patient set included all patients in the TS who had the study baseline and at least 1 evaluable post-dose measurement for 1 of the primary endpoints. Assignment to the FAS was done after implementation of any data handling rules,which set measurements to missing.
Inspiratory capacity (IC) at rest before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap). Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1. The presented means are adjusted means from the MMRM (Mixed Effects Model Repeated Measures) model.
Outcome measures
| Measure |
Placebo
n=211 Participants
Oral inhalation of placebo, 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Olodaterol 5 µg
n=214 Participants
Oral inhalation of Olodaterol fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium 5 µg
n=213 Participants
Oral inhalation of Tiotropium fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 2.5/5
n=214 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg (Tiotropium: 1.25 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 5/5
n=219 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
|---|---|---|---|---|---|
|
Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
|
2.440 Litres
Standard Error 0.027
|
2.566 Litres
Standard Error 0.027
|
2.571 Litres
Standard Error 0.027
|
2.658 Litres
Standard Error 0.027
|
2.685 Litres
Standard Error 0.027
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: FAS
Endurance time during constant work rate cycle ergometry (CWRCE) to symptom limitation at 75% work capacity (Wcap). Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1. The presented means are adjusted mean from the MMRM model.
Outcome measures
| Measure |
Placebo
n=209 Participants
Oral inhalation of placebo, 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Olodaterol 5 µg
n=208 Participants
Oral inhalation of Olodaterol fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium 5 µg
n=209 Participants
Oral inhalation of Tiotropium fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 2.5/5
n=212 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg (Tiotropium: 1.25 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 5/5
n=212 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
|---|---|---|---|---|---|
|
Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
|
375.45 seconds
Standard Error 12.037
|
453.38 seconds
Standard Error 14.552
|
457.16 seconds
Standard Error 14.652
|
474.80 seconds
Standard Error 15.145
|
454.08 seconds
Standard Error 14.474
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: FAS
Slope of the intensity of breathing discomfort during Constant Work Rate Cycle Ergometry (CWRCE) to symptom limitation at 75% Work capacity (Wcap). The intensity of breathing discomfort was rated using the modified Borg scale with ratings from 0 (nothing at all) to 10 (maximal). Slope of breathing discomfort is defined as: (intensity of breathing discomfort at the end of exercise minus intensity of breathing discomfort at rest) / endurance time. A decrease in slope indicates improvement. The presented means are adjusted means from MMRM model.
Outcome measures
| Measure |
Placebo
n=209 Participants
Oral inhalation of placebo, 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Olodaterol 5 µg
n=208 Participants
Oral inhalation of Olodaterol fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium 5 µg
n=209 Participants
Oral inhalation of Tiotropium fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 2.5/5
n=212 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg (Tiotropium: 1.25 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 5/5
n=212 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
|---|---|---|---|---|---|
|
Slope of the Intensity of Breathing Discomfort During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity
|
0.018 units on a scale / second
Standard Error 0.001
|
0.016 units on a scale / second
Standard Error 0.001
|
0.016 units on a scale / second
Standard Error 0.001
|
0.015 units on a scale / second
Standard Error 0.001
|
0.016 units on a scale / second
Standard Error 0.001
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: FAS
Forced Expiratory Volume in 1 Second (FEV1) (one hour post-dose) The presented means are adjusted means from MMRM model.
Outcome measures
| Measure |
Placebo
n=216 Participants
Oral inhalation of placebo, 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Olodaterol 5 µg
n=214 Participants
Oral inhalation of Olodaterol fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium 5 µg
n=218 Participants
Oral inhalation of Tiotropium fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 2.5/5
n=216 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg (Tiotropium: 1.25 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 5/5
n=224 Participants
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (One Hour Post-dose)
|
1.497 Litres
Standard Error 0.013
|
1.689 Litres
Standard Error 0.013
|
1.706 Litres
Standard Error 0.013
|
1.783 Litres
Standard Error 0.013
|
1.820 Litres
Standard Error 0.013
|
Adverse Events
Placebo
Serious events: 4 serious events
Other events: 26 other events
Deaths: 0 deaths
Olodaterol 5 µg
Serious events: 3 serious events
Other events: 17 other events
Deaths: 0 deaths
Tiotropium 5 µg
Serious events: 8 serious events
Other events: 20 other events
Deaths: 0 deaths
Tiotropium + Olodaterol 2.5/5
Serious events: 5 serious events
Other events: 13 other events
Deaths: 0 deaths
Tiotropium + Olodaterol 5/5
Serious events: 6 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=222 participants at risk
Oral inhalation of placebo, 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Olodaterol 5 µg
n=217 participants at risk
Oral inhalation of Olodaterol fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium 5 µg
n=226 participants at risk
Oral inhalation of Tiotropium fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 2.5/5
n=222 participants at risk
Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg (Tiotropium: 1.25 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 5/5
n=226 participants at risk
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.46%
1/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Cardiac disorders
Bradycardia
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Congenital, familial and genetic disorders
Congenital cystic kidney disease
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
General disorders
Chest discomfort
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
General disorders
Chest pain
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
General disorders
Hypothermia
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Hepatobiliary disorders
Biliary tract disorder
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Infections and infestations
Kidney infection
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Infections and infestations
Pneumonia
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.88%
2/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Infections and infestations
Wound abscess
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Injury, poisoning and procedural complications
Splenic rupture
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blepharal papilloma
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.46%
1/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.46%
1/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Nervous system disorders
Vertebrobasilar insufficiency
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.88%
2/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.44%
1/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
|
Vascular disorders
Haematoma
|
0.00%
0/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/217 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
0.45%
1/222 • From drug administration until 21 days after the last administration, up to 120 days
|
0.00%
0/226 • From drug administration until 21 days after the last administration, up to 120 days
|
Other adverse events
| Measure |
Placebo
n=222 participants at risk
Oral inhalation of placebo, 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Olodaterol 5 µg
n=217 participants at risk
Oral inhalation of Olodaterol fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium 5 µg
n=226 participants at risk
Oral inhalation of Tiotropium fixed dose 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 2.5/5
n=222 participants at risk
Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 µg and Olodaterol 5 µg (Tiotropium: 1.25 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
Tiotropium + Olodaterol 5/5
n=226 participants at risk
Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
11.7%
26/222 • From drug administration until 21 days after the last administration, up to 120 days
|
7.8%
17/217 • From drug administration until 21 days after the last administration, up to 120 days
|
8.8%
20/226 • From drug administration until 21 days after the last administration, up to 120 days
|
5.9%
13/222 • From drug administration until 21 days after the last administration, up to 120 days
|
8.4%
19/226 • From drug administration until 21 days after the last administration, up to 120 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER