Trial Outcomes & Findings for Efficacy and Safety of 4 Weeks of Treatment With Orally Inhaled BI1744/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00720499)

NCT ID: NCT00720499

Last Updated: 2015-08-17

Results Overview

Trough FEV1 was defined as the mean of the 2 FEV1 values at the end of the dosing interval, 24 hours post-drug administration. Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period. The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 141 participants
• Primary outcome timeframe: 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29
• Results posted on: 2015-08-17

Participant Flow

This was a randomised, 2-way cross-over trial. 141 patients were randomized to one of 2 treatments sequences and treated. It was a double-blind trial in which each treatment period lasted 4 weeks. During the 2 week pre-treatment run-in and during the 2 week washout between treatment periods, patients received open-label tiotropium 5µg.

Participant milestones

Measure	Tio+Olo 5/2µg / Tio+Olo5/5µg Patients received fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 2 µg followed by fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 5 µg. Both treatments were administered once daily in the morning via the respimat inhaler.	Tio+Olo5/5µg / Tio+Olo5/2µg Patients received fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 5 µg followed by fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 2 µg. Both treatments were administered once daily in the morning via the respimat inhaler.
Treatment Period 1 (4 Weeks) STARTED	69	72
Treatment Period 1 (4 Weeks) COMPLETED	66	70
Treatment Period 1 (4 Weeks) NOT COMPLETED	3	2
Washout Period (2 Weeks) STARTED	66	70
Washout Period (2 Weeks) COMPLETED	66	70
Washout Period (2 Weeks) NOT COMPLETED	0	0
Treatment Period 2 (4 Weeks) STARTED	66	70
Treatment Period 2 (4 Weeks) COMPLETED	64	67
Treatment Period 2 (4 Weeks) NOT COMPLETED	2	3

Reasons for withdrawal

Measure	Tio+Olo 5/2µg / Tio+Olo5/5µg Patients received fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 2 µg followed by fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 5 µg. Both treatments were administered once daily in the morning via the respimat inhaler.	Tio+Olo5/5µg / Tio+Olo5/2µg Patients received fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 5 µg followed by fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol (BI1744) 2 µg. Both treatments were administered once daily in the morning via the respimat inhaler.
Treatment Period 1 (4 Weeks) Adverse Event	2	0
Treatment Period 1 (4 Weeks) Protocol Violation	1	2
Treatment Period 2 (4 Weeks) Adverse Event	2	3

Baseline Characteristics

Efficacy and Safety of 4 Weeks of Treatment With Orally Inhaled BI1744/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	Overall Study n=141 Participants A randomised, double-blind, 2-way cross-over study. The two treatment periods were separated by a wash-out period of 14 days during which they received open-label Tiotropium 5 mcg. The 2 treatments, administered once daily in the morning via the respimat inhaler, were : * Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg * Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 5 µg
Age, Continuous	63.67 years STANDARD_DEVIATION 8.19 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants
Sex: Female, Male Male	93 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

Population: Full analysis Set (FAS) which included all randomized patients who received at least one dose of study medication and had baseline data and Washout Period for at least 1 efficacy endpoint for each treatment period.

Trough FEV1 was defined as the mean of the 2 FEV1 values at the end of the dosing interval, 24 hours post-drug administration.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment.	0.057 Litres Standard Error 0.013	0.055 Litres Standard Error 0.013

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15

Population: FAS

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
Trough FEV1 Response [L] After 2 Weeks of Treatment	0.037 Litres Standard Error 0.015	0.059 Litres Standard Error 0.015

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

Population: FAS

Individual FEV1 measurements [L] at each time point on Day 29.

The presented means are adjusted.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
Individual FEV1 Measurements 3:00	1.601 Litres Standard Error 0.015	1.606 Litres Standard Error 0.015
Individual FEV1 Measurements 4:00	1.582 Litres Standard Error 0.016	1.606 Litres Standard Error 0.016
Individual FEV1 Measurements -1:00	1.426 Litres Standard Error 0.013	1.417 Litres Standard Error 0.013
Individual FEV1 Measurements -0:10	1.434 Litres Standard Error 0.014	1.438 Litres Standard Error 0.014
Individual FEV1 Measurements 0:05	1.497 Litres Standard Error 0.014	1.498 Litres Standard Error 0.014
Individual FEV1 Measurements 0:30	1.541 Litres Standard Error 0.012	1.534 Litres Standard Error 0.012
Individual FEV1 Measurements 1:00	1.570 Litres Standard Error 0.012	1.570 Litres Standard Error 0.012
Individual FEV1 Measurements 2:00	1.617 Litres Standard Error 0.012	1.614 Litres Standard Error 0.012
Individual FEV1 Measurements 5:00	1.571 Litres Standard Error 0.013	1.570 Litres Standard Error 0.014
Individual FEV1 Measurements 6:00	1.547 Litres Standard Error 0.013	1.551 Litres Standard Error 0.013

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

Population: FAS

FEV1 Area Under the Curve (AUC) 0-3h, response [L] on days 1, 15 and 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
FEV1 AUC 0-3h, Response Day 1	0.168 Litres Standard Error 0.006	0.173 Litres Standard Error 0.006
FEV1 AUC 0-3h, Response Day 15	0.174 Litres Standard Error 0.012	0.194 Litres Standard Error 0.012
FEV1 AUC 0-3h, Response Day 29	0.201 Litres Standard Error 0.011	0.200 Litres Standard Error 0.011

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

Population: FAS

FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response [L] on days 1, 15 and 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
FEV1 Peak 0-3h Response Day 1	0.269 Litres Standard Error 0.008	0.262 Litres Standard Error 0.008
FEV1 Peak 0-3h Response Day 15	0.257 Litres Standard Error 0.014	0.279 Litres Standard Error 0.015
FEV1 Peak 0-3h Response Day 29	0.288 Litres Standard Error 0.014	0.294 Litres Standard Error 0.014

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

Population: FAS

FEV1, AUC (0-6h) response [L] on day 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
FEV1, AUC (0-6h) Response	0.202 Litres Standard Error 0.012	0.206 Litres Standard Error 0.012

SECONDARY outcome

Timeframe: 6 hours (h), 9h and 12h after drug administration on day 29

Population: FAS

FEV1 (unsupervised) AUC (6-12h) response [L] on day 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=130 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=132 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.
FEV1 (Unsupervised) AUC (6-12h) Response	0.106 Litres Standard Error 0.029	0.114 Litres Standard Error 0.029

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15, in addition 4h, 5h, 6h after drug administration on day 29

Population: FAS

Trough Forced Vital Capacity (FVC) response [L] on days 15 and 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
Trough FVC Response Day 15	0.072 Litres Standard Error 0.024	0.104 Litres Standard Error 0.025
Trough FVC Response Day 29	0.066 Litres Standard Error 0.022	0.076 Litres Standard Error 0.023

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

Population: FAS

Individual FVC measurements [L] at each time point

The categories correspond to the planned times for FVC measurements on Day 29.

The presented means are adjusted.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
Individual FVC Measurements 5:00	3.109 Litres Standard Error 0.025	3.131 Litres Standard Error 0.025
Individual FVC Measurements -1:00	2.894 Litres Standard Error 0.023	2.899 Litres Standard Error 0.024
Individual FVC Measurements -0:10	2.892 Litres Standard Error 0.024	2.907 Litres Standard Error 0.024
Individual FVC Measurements 0:05	3.009 Litres Standard Error 0.024	3.032 Litres Standard Error 0.025
Individual FVC Measurements 0:30	3.067 Litres Standard Error 0.023	3.083 Litres Standard Error 0.024
Individual FVC Measurements 1:00	3.093 Litres Standard Error 0.023	3.112 Litres Standard Error 0.023
Individual FVC Measurements 2:00	3.154 Litres Standard Error 0.023	3.189 Litres Standard Error 0.023
Individual FVC Measurements 3:00	3.147 Litres Standard Error 0.037	3.201 Litres Standard Error 0.038
Individual FVC Measurements 4:00	3.143 Litres Standard Error 0.039	3.204 Litres Standard Error 0.040
Individual FVC Measurements 6:00	3.061 Litres Standard Error 0.023	3.083 Litres Standard Error 0.023

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

Population: FAS

FVC AUC (0-3h) response [L] on days 1, 15 and 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
FVC AUC (0-3h) Response Day 1	0.273 Litres Standard Error 0.012	0.275 Litres Standard Error 0.012
FVC AUC (0-3h) Response Day 15	0.271 Litres Standard Error 0.020	0.308 Litres Standard Error 0.021
FVC AUC (0-3h) Response Day 29	0.275 Litres Standard Error 0.021	0.303 Litres Standard Error 0.022

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

Population: FAS

FVC AUC (0-6h) response [L] on day 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
FVC AUC (0-6h) Response	0.283 Litres Standard Error 0.023	0.318 Litres Standard Error 0.024

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 29

Population: FAS

FVC peak 0-3h response [L] on day 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
FVC Peak 0-3h Response	0.444 Litres Standard Error 0.033	0.490 Litres Standard Error 0.034

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

Population: FAS

Peak Expiratory Flow Rate (PEFR) AUC (0-3h) response [L/min] on days 1, 15 and 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
PEFR AUC (0-3h) Response Day 1	27.159 Litres / minute Standard Error 1.604	28.143 Litres / minute Standard Error 1.619
PEFR AUC (0-3h) Response Day 15	27.817 Litres / minute Standard Error 2.483	34.128 Litres / minute Standard Error 2.507
PEFR AUC (0-3h) Response Day 29	32.395 Litres / minute Standard Error 2.101	33.947 Litres / minute Standard Error 2.121

SECONDARY outcome

Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

Population: FAS

PEFR peak 0-3h response [L/min] on days 1, 15 and 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=136 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
PEFR Peak 0-3h Response Day 1	49.125 Litres / minute Standard Error 1.843	48.946 Litres / minute Standard Error 1.861
PEFR Peak 0-3h Response Day 15	46.355 Litres / minute Standard Error 2.801	52.835 Litres / minute Standard Error 2.827
PEFR Peak 0-3h Response Day 29	52.497 Litres / minute Standard Error 2.466	55.596 Litres / minute Standard Error 2.490

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes before drug administration on day 1 and 6h, 9h and 12h after drug administration on day 29

Population: FAS

PEFR AUC (6-12h) response [L] on day 29.

Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.

The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed).

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=130 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=132 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.
PEFR AUC (6-12h) Response	24.830 Litres / minute Standard Error 3.634	24.130 Litres / minute Standard Error 3.599

SECONDARY outcome

Timeframe: Weeks 1,2,3 and 4

Population: FAS

Weekly mean morning PEFR [L/min] on weeks 1,2,3 and 4.

The presented means are adjusted.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=131 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=132 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.
Weekly Mean Morning PEFR Week 2	242.38 Litres / minute Standard Error 1.842	243.72 Litres / minute Standard Error 1.821
Weekly Mean Morning PEFR Week 1	244.16 Litres / minute Standard Error 1.713	245.28 Litres / minute Standard Error 1.693
Weekly Mean Morning PEFR Week 3	242.31 Litres / minute Standard Error 1.805	242.97 Litres / minute Standard Error 1.784
Weekly Mean Morning PEFR Week 4	242.90 Litres / minute Standard Error 2.000	244.56 Litres / minute Standard Error 1.977

SECONDARY outcome

Timeframe: Weeks 1,2,3 and 4

Population: FAS

Weekly mean evening PEFR [L/min] on weeks 1,2,3 and 4.

The presented means are adjusted.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=131 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=130 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.
Weekly Mean Evening PEFR Week 1	262.21 Litres / minute Standard Error 2.026	265.51 Litres / minute Standard Error 2.024
Weekly Mean Evening PEFR Week 2	261.08 Litres / minute Standard Error 2.146	262.47 Litres / minute Standard Error 2.144
Weekly Mean Evening PEFR Week 3	258.62 Litres / minute Standard Error 1.959	260.32 Litres / minute Standard Error 1.956
Weekly Mean Evening PEFR Week 4	261.38 Litres / minute Standard Error 1.942	260.34 Litres / minute Standard Error 1.940

SECONDARY outcome

Timeframe: Weeks 1,2,3 and 4

Population: FAS

Weekly mean number of occasions of rescue therapy used per day (as occasion require (PRN) salbutamol [albuterol]) on weeks 1,2,3 and 4.

The means presented are the adjusted mean of weekly mean.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=131 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=132 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.
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) Week 1	1.294 number of occasions / day Standard Error 0.063	1.305 number of occasions / day Standard Error 0.062
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) Week 2	1.472 number of occasions / day Standard Error 0.068	1.352 number of occasions / day Standard Error 0.067
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) Week 3	1.369 number of occasions / day Standard Error 0.071	1.367 number of occasions / day Standard Error 0.070
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol]) Week 4	1.403 number of occasions / day Standard Error 0.071	1.363 number of occasions / day Standard Error 0.069

SECONDARY outcome

Timeframe: 4 weeks

Population: FAS

Patient global rating scores treatment comparison after 4 weeks

The score was evaluated on a 7-point scale :

• 1 : very much better
• 2 : much better
• 3 : a little better
• 4 : no change
• 5 : a little worse
• 6 : much worse
• 7 : very much worse

The presented means are adjusted.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=133 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=135 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.
Patient Global Rating	3.207 units on a scale Standard Error 0.091	3.093 units on a scale Standard Error 0.090

SECONDARY outcome

Timeframe: Days 15 and 29

Population: FAS

Physician's global evaluation score on days 15 and 29

The score was evaluated on a 8-points scale :

• Poor : 1,2
• Fair : 3,4
• Good : 5,6
• Excellent : 7,8

The presented means are adjusted

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=135 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=136 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.
Physician's Global Evaluation Day 15	5.084 units on a scale Standard Error 0.070	5.079 units on a scale Standard Error 0.070
Physician's Global Evaluation Day 29	5.085 units on a scale Standard Error 0.063	5.065 units on a scale Standard Error 0.063

SECONDARY outcome

Timeframe: 14 weeks

Population: Treated Set (TS) including all randomized patients who received at least one dose of study medication.

Clinically significant abnormalities for blood chemistry, haematology, urinalysis and physical examination

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=138 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination Urinalysis	0 participants	0 participants
Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination Creatinine phosphokinase increased	8 participants	7 participants
Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination Eosinophils increased	3 participants	3 participants

SECONDARY outcome

Timeframe: Baseline to week 14

Population: TS

Overall marked changes from baseline in systolic blood pressure, diastolic blood pressure and pulse rate.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
Overall Marked Changes From Baseline in Vital Signs Systolic blood pressure increased	16 participants	23 participants
Overall Marked Changes From Baseline in Vital Signs Systolic blood pressure decreased	10 participants	11 participants
Overall Marked Changes From Baseline in Vital Signs Diastolic blood pressure increased	19 participants	15 participants
Overall Marked Changes From Baseline in Vital Signs Diastolic blood pressure decreased	13 participants	17 participants
Overall Marked Changes From Baseline in Vital Signs Pulse rate increased	10 participants	13 participants
Overall Marked Changes From Baseline in Vital Signs Pulse rate decreased	19 participants	10 participants

SECONDARY outcome

Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

Population: TS

12-lead Electrocardiogram (ECG) Heart rate baseline and change from baseline values at other time points in Beats Per Minute (BPM)

Statistics for each planned time from baseline to day 29.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
12-lead ECG Heart Rate Baseline	72.96 BPM Standard Deviation 12.86	72.38 BPM Standard Deviation 11.96
12-lead ECG Heart Rate Day1 0:10	-1.44 BPM Standard Deviation 6.04	-1.01 BPM Standard Deviation 5.63
12-lead ECG Heart Rate Day1 1:00	-2.09 BPM Standard Deviation 7.6	-1.6 BPM Standard Deviation 7.45
12-lead ECG Heart Rate Day15 -0:30 (N=137, 137)	0.42 BPM Standard Deviation 11.09	1.1 BPM Standard Deviation 8.88
12-lead ECG Heart Rate Day15 0:10 (N=135, 136)	-1.61 BPM Standard Deviation 8.77	-0.79 BPM Standard Deviation 8.97
12-lead ECG Heart Rate Day29 -0:30 (N=134, 136)	-0.69 BPM Standard Deviation 8.71	1.68 BPM Standard Deviation 9.43
12-lead ECG Heart Rate Day29 0:10 (N=132, 135)	-2.14 BPM Standard Deviation 9.25	-0.24 BPM Standard Deviation 9.5
12-lead ECG Heart Rate Day29 1:00 (N=132, 135)	-2.34 BPM Standard Deviation 9.75	-0.73 BPM Standard Deviation 8.98

SECONDARY outcome

Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

Population: TS

12-lead ECG PR intervals baseline and change from baseline at other timepoints in milliseconds.

Statistics for each planned time from baseline to day 29.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
12-lead ECG PR Intervals Baseline	160.03 mS Standard Deviation 24.94	160.69 mS Standard Deviation 29.28
12-lead ECG PR Intervals Day1 0:10	-1.02 mS Standard Deviation 12.05	-1.86 mS Standard Deviation 17.53
12-lead ECG PR Intervals Day1 1:00 (N=139, 137)	2.12 mS Standard Deviation 13.94	0.09 mS Standard Deviation 11.07
12-lead ECG PR Intervals Day15 -0:30 (N=136, 137)	0.55 mS Standard Deviation 12.56	-0.95 mS Standard Deviation 20.17
12-lead ECG PR Intervals Day15 0:10 (N=135, 136)	0.28 mS Standard Deviation 12.17	-1.24 mS Standard Deviation 15.08
12-lead ECG PR Intervals Day29 -0:30 (N=134, 135)	-1.29 mS Standard Deviation 13.45	-0.19 mS Standard Deviation 15.35
12-lead ECG PR Intervals Day29 0:10 (N=132, 135)	-0.29 mS Standard Deviation 13.9	-2.05 mS Standard Deviation 16.39
12-lead ECG PR Intervals Day29 1:00 (N=132, 135)	1.98 mS Standard Deviation 17.91	0.22 mS Standard Deviation 13.05

SECONDARY outcome

Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

Population: TS

12-lead ECG QRS intervals baseline and change from baseline at other time points in milliseconds

Statistics for each planned time from baseline to day 29.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
12-lead ECG QRS Intervals Day29 0:10 (N=132, 135)	-1.27 mS Standard Deviation 6.63	-0.82 mS Standard Deviation 7.16
12-lead ECG QRS Intervals Baseline	92.71 mS Standard Deviation 11.92	92.41 mS Standard Deviation 12.14
12-lead ECG QRS Intervals Day1 0:10	-0.28 mS Standard Deviation 6.29	-0.65 mS Standard Deviation 6.63
12-lead ECG QRS Intervals Day1 1:00	-0.47 mS Standard Deviation 6.39	0.31 mS Standard Deviation 6.34
12-lead ECG QRS Intervals Day15 -0:30 (N=137, 137)	-0.55 mS Standard Deviation 7.48	-0.44 mS Standard Deviation 7.73
12-lead ECG QRS Intervals Day15 0:10 (N=135, 136)	-0.67 mS Standard Deviation 6.73	-0.32 mS Standard Deviation 7.9
12-lead ECG QRS Intervals Day29 -0:30 (N=134, 136)	-0.44 mS Standard Deviation 7.55	-0.75 mS Standard Deviation 7.4
12-lead ECG QRS Intervals Day29 1:00 (N=132, 135)	-0.33 mS Standard Deviation 7.5	-0.39 mS Standard Deviation 7.9

SECONDARY outcome

Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

Population: TS

12-lead ECG corrected heart rate (QT) interval, using Fridericia method (QTcF), baseline and change from baseline at other time points in milliseconds.

Statistics for each planned time from baseline to day 29.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
12-lead ECG QTcF Intervals Baseline	405.63 mS Standard Deviation 21.42	403.53 mS Standard Deviation 20.49
12-lead ECG QTcF Intervals Day1 0:10	-0.89 mS Standard Deviation 12.85	0.97 mS Standard Deviation 13.49
12-lead ECG QTcF Intervals Day1 1:00 (N=138, 138)	-0.69 mS Standard Deviation 12.79	-0.61 mS Standard Deviation 15.19
12-lead ECG QTcF Intervals Day15 -0:30 (N=137, 137)	0.55 mS Standard Deviation 14.28	-0.03 mS Standard Deviation 16.5
12-lead ECG QTcF Intervals Day15 0:10 (N=135, 136)	-1.16 mS Standard Deviation 16.67	-1.02 mS Standard Deviation 17.37
12-lead ECG QTcF Intervals Day29 -0:30 (N=134, 136)	-1.35 mS Standard Deviation 17.18	-0.24 mS Standard Deviation 17.39
12-lead ECG QTcF Intervals Day29 0:10 (N=132, 135)	-1.22 mS Standard Deviation 15.05	-2.08 mS Standard Deviation 16.56
12-lead ECG QTcF Intervals Day29 1:00 (N=132, 135)	-0.56 mS Standard Deviation 18.24	-1.05 mS Standard Deviation 16.49

SECONDARY outcome

Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

Population: TS

12-lead ECG heart rate corrected QT interval, using Bazett method (QTcB), baseline and change from baseline at other time points in milliseconds.

Statistics for each planned time from baseline to day 29.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
12-lead ECG QTcB Intervals Baseline	418.12 mS Standard Deviation 24.67	415.56 mS Standard Deviation 23.35
12-lead ECG QTcB Intervals Day1 0:10	-2.18 mS Standard Deviation 16.32	0.05 mS Standard Deviation 16.14
12-lead ECG QTcB Intervals Day1 1:00 (N=138, 138)	-2.57 mS Standard Deviation 15.95	-2.2 mS Standard Deviation 18.05
12-lead ECG QTcB Intervals Day15 -0:30 (N=137, 137)	0.93 mS Standard Deviation 18.23	0.91 mS Standard Deviation 19.72
12-lead ECG QTcB Intervals Day15 0:10 (N=135, 136)	-2.51 mS Standard Deviation 20.37	-1.76 mS Standard Deviation 20.51
12-lead ECG QTcB Intervals Day29 -0:30 (N=134, 136)	-1.87 mS Standard Deviation 20.43	1.43 mS Standard Deviation 21.52
12-lead ECG QTcB Intervals Day29 0:10 (N=132, 135)	-3.13 mS Standard Deviation 19.45	-2.33 mS Standard Deviation 20.35
12-lead ECG QTcB Intervals Day29 1:00 (N=132, 135)	-2.55 mS Standard Deviation 23.88	-1.69 mS Standard Deviation 19.75

SECONDARY outcome

Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

Population: TS

12-lead ECG QT intervals baseline and change from baseline at other time points in milliseconds.

Statistics for each planned time from baseline to day 29.

Outcome measures

Measure	Olo 2 µg + Tio 5 µg n=139 Participants Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
12-lead ECG QT Intervals Baseline	382.73 mS Standard Deviation 31.87	381.33 mS Standard Deviation 29.42
12-lead ECG QT Intervals Day1 0:10	1.59 mS Standard Deviation 13.09	2.69 mS Standard Deviation 13.82
12-lead ECG QT Intervals Day1 1:00 (N=138, 138)	2.97 mS Standard Deviation 15.89	2.33 mS Standard Deviation 18.02
12-lead ECG QT Intervals Day15 -0:30 (N=137, 137)	-0.09 mS Standard Deviation 19.95	-1.76 mS Standard Deviation 20.16
12-lead ECG QT Intervals Day15 0:10 (N=135, 136)	1.44 mS Standard Deviation 20.59	0.53 mS Standard Deviation 21.28
12-lead ECG QT Intervals Day29 -0:30 (N=134, 136)	-0.59 mS Standard Deviation 20.91	-3.14 mS Standard Deviation 20.13
12-lead ECG QT Intervals Day29 0:10 (N=132, 135)	2.27 mS Standard Deviation 19.24	-1.73 mS Standard Deviation 20.83
12-lead ECG QT Intervals Day29 1:00 (N=132, 135)	3.14 mS Standard Deviation 19.28	0.2 mS Standard Deviation 20.51

SECONDARY outcome

Timeframe: 4 weeks

Population: No patients analyzed in the study report.

• AUC (0-6h) for FEV1, and PEFR (unsupervised) after first dose and after 2 and 4 weeks of treatment were not analysed in the study report because the pertinent information from the unsupervised Pulmonary Function Tests (PFTs) was for the time interval from 6 to 12 hours post-dosing.
• FVC peak 0-3h response after the first dose and at Week 2 (supervised) and AUC (6-12h) for FEV1 and PEFR after the first dose and at Week 2 (unsupervised) were not analysed in the study report.
• Individual PEFR (supervised) measurements and individual FEV1 and PEFR (unsupervised) measurements at each time point were not analysed in the study report.

Outcome measures

Outcome data not reported

Adverse Events

Olo 2 µg + Tio 5 µg

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Olo 5 µg + Tio5 µg

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olo 2 µg + Tio 5 µg n=139 participants at risk Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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 Arteriosclerosis coronary artery	0.72% 1/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.00% 0/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Cardiac disorders Cardiac failure	0.72% 1/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.00% 0/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Cardiac disorders Coronary artery disease	0.72% 1/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.72% 1/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Gastrointestinal disorders Enteritis	0.00% 0/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.72% 1/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Infections and infestations Pneumonia	0.00% 0/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.72% 1/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.72% 1/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Nervous system disorders Cerebral infarction	0.72% 1/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.00% 0/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Nervous system disorders Intracranial aneurysm	0.72% 1/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	0.00% 0/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	1.4% 2/138 • From drug administration until 14 days after the last administration, up to 12 weeks.

Other adverse events

Measure	Olo 2 µg + Tio 5 µg n=139 participants at risk Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 2 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 1.0 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning.	Olo 5 µg + Tio5 µg n=138 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.
Infections and infestations Nasopharyngitis	10.8% 15/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	7.2% 10/138 • From drug administration until 14 days after the last administration, up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	5.8% 8/139 • From drug administration until 14 days after the last administration, up to 12 weeks.	5.8% 8/138 • From drug administration until 14 days after the last administration, up to 12 weeks.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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