Trial Outcomes & Findings for Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Japanese Patients With COPD (NCT NCT00824382)

NCT ID: NCT00824382

Last Updated: 2014-06-27

Results Overview

The change from baseline in trough FEV1 after 4 weeks of treatment. Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to next test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline . Baseline trough FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 prior to administration of the first dose of study medication.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 328 participants
• Primary outcome timeframe: baseline and after 4 weeks treatment
• Results posted on: 2014-06-27

Participant Flow

The first patient was enrolled in the trial on 13 January 2009 and the last patient made the last visit on 31 March 2010. A total of 515 patients were enrolled in the trial at 48 trial sites. Of the 515 patients, 328 patients were entered in the trial and were randomly assigned to receive either one of the four treatments for 4 weeks.

Informed consent was obtained prior to patient participation in the trial, which included medication washout procedures or restrictions. Upon obtaining consent, the patients were instructed on the medication washout and other restrictions for the screening PFT (Visit 1).

Participant milestones

Measure	Placebo Placebo	Olodaterol 2mcg Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg Olodaterol 10mcg inhalation solution via Respimat
Overall Study STARTED	79	84	79	86
Overall Study COMPLETED	74	82	76	81
Overall Study NOT COMPLETED	5	2	3	5

Reasons for withdrawal

Measure	Placebo Placebo	Olodaterol 2mcg Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg Olodaterol 10mcg inhalation solution via Respimat
Overall Study Adverse Event	4	1	1	4
Overall Study Protocol Violation	1	0	0	1
Overall Study Investigator's decision	0	1	2	0

Baseline Characteristics

Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Japanese Patients With COPD

Baseline characteristics by cohort

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat	Total n=328 Participants Total of all reporting groups
Age, Continuous	68.9 years STANDARD_DEVIATION 6.5 • n=5 Participants	68.9 years STANDARD_DEVIATION 7.6 • n=7 Participants	70.1 years STANDARD_DEVIATION 6.7 • n=5 Participants	69.3 years STANDARD_DEVIATION 7.4 • n=4 Participants	69.3 years STANDARD_DEVIATION 7.1 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	18 Participants n=21 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	79 Participants n=7 Participants	76 Participants n=5 Participants	80 Participants n=4 Participants	310 Participants n=21 Participants
Percent predicted normal FEV1	50.64 percent STANDARD_DEVIATION 12.32 • n=5 Participants	51.36 percent STANDARD_DEVIATION 14.15 • n=7 Participants	52.07 percent STANDARD_DEVIATION 12.82 • n=5 Participants	51.73 percent STANDARD_DEVIATION 11.81 • n=4 Participants	51.45 percent STANDARD_DEVIATION 12.76 • n=21 Participants
Percent predicted normal FEV1 < 30%	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Percent predicted normal FEV1 30 to < 50%	35 Participants n=5 Participants	40 Participants n=7 Participants	38 Participants n=5 Participants	41 Participants n=4 Participants	154 Participants n=21 Participants
Percent predicted normal FEV1 50% to 80%	43 Participants n=5 Participants	43 Participants n=7 Participants	41 Participants n=5 Participants	45 Participants n=4 Participants	172 Participants n=21 Participants

PRIMARY outcome

Timeframe: baseline and after 4 weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period - analysis with imputation

The change from baseline in trough FEV1 after 4 weeks of treatment. Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to next test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline . Baseline trough FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 prior to administration of the first dose of study medication.

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Trough FEV1 Response at Week 4	-0.032 Liter Standard Error 0.015	0.059 Liter Standard Error 0.015	0.100 Liter Standard Error 0.015	0.100 Liter Standard Error 0.015

SECONDARY outcome

Timeframe: baseline and after 2 weeks treatment

Population: The full analysis set (FAS) - analysis with imputation

Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to next test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline trough FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 prior to administration of the first dose of study medication

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Trough FEV1 Response at Week 2	-0.020 Liter Standard Error 0.016	0.061 Liter Standard Error 0.015	0.120 Liter Standard Error 0.016	0.136 Liter Standard Error 0.015

SECONDARY outcome

Timeframe: baseline and after 4 weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period - analysis with imputation

The change from baseline in FEV1 AUC(0-3) after 4 weeks of treatment. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in liters.

Due to normalization the unit is liters.

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
FEV1 AUC(0-3) Response at 4 Weeks	-0.020 Liter Standard Error 0.017	0.118 Liter Standard Error 0.016	0.177 Liter Standard Error 0.017	0.173 Liter Standard Error 0.016

SECONDARY outcome

Timeframe: baseline and after 4 weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period - analysis with imputation

The change from baseline in FEV1 peak(0-3) after 4 weeks of treatment.

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
FEV1 Peak(0-3) Response at 4 Weeks	0.025 Liter Standard Error 0.017	0.170 Liter Standard Error 0.017	0.227 Liter Standard Error 0.017	0.220 Liter Standard Error 0.017

SECONDARY outcome

Timeframe: baseline and after 4 weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period - analysis with imputation

The change from baseline in Trough FVC after 4 weeks of treatment

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Trough FVC Response at Week 4	-0.037 Liter Standard Error 0.033	0.154 Liter Standard Error 0.032	0.154 Liter Standard Error 0.033	0.150 Liter Standard Error 0.032

SECONDARY outcome

Timeframe: baseline and after 4 weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period - analysis with imputation

The change from baseline in FVC AUC(0-3) response after 4 weeks of treatment. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in liters.

Due to normalization the unit is liters.

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
FVC AUC(0-3) Response	0.004 Liter Standard Error 0.036	0.257 Liter Standard Error 0.035	0.254 Liter Standard Error 0.036	0.237 Liter Standard Error 0.035

SECONDARY outcome

Timeframe: baseline and after 4 weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period - analysis with imputation

The change from baseline in FVC peak(0-3) response after 4 weeks of treatment.

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
FVC Peak(0-3) Response	0.109 Liter Standard Error 0.038	0.362 Liter Standard Error 0.037	0.351 Liter Standard Error 0.038	0.335 Liter Standard Error 0.036

SECONDARY outcome

Timeframe: baseline and after 4weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period which is however restricted to patients with evaluable data for this endpoint - analysis with imputation

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect.

FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in liters.

Outcome measures

Measure	Placebo n=78 Participants Placebo	Olodaterol 2mcg n=80 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=85 Participants Olodaterol 10mcg inhalation solution via Respimat
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 0-6h (AUC 0-6h) Response After 4 Weeks	-0.022 Liter Standard Error 0.028	0.090 Liter Standard Error 0.027	0.195 Liter Standard Error 0.027	0.195 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline and after 4weeks treatment

Population: The full analysis set (FAS) for 4 weeks treatment period which is however restricted to patients with evaluable data for this endpoint - analysis with imputation

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect.

FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in liters.

Outcome measures

Measure	Placebo n=78 Participants Placebo	Olodaterol 2mcg n=80 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=85 Participants Olodaterol 10mcg inhalation solution via Respimat
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks	-0.005 Liter Standard Error 0.028	0.078 Liter Standard Error 0.027	0.171 Liter Standard Error 0.027	0.186 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: Week 4

Population: The full analysis set (FAS) for 4 weeks treatment period which is however restricted to patients with evaluable data for this endpoint - analysis with imputation

PEFR measurements were recorded by means of a patient diary on a daily basis. This diary was used to record the twice daily PEFs,

Morning measurements were performed immediately upon arising before administration of trial and/or rescue medication.The highest of three readings for each measurement were recorded.

Outcome measures

Measure	Placebo n=78 Participants Placebo	Olodaterol 2mcg n=83 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=78 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks	217.54 Liter/minute Standard Error 4.059	244.80 Liter/minute Standard Error 3.933	246.93 Liter/minute Standard Error 4.059	254.22 Liter/minute Standard Error 3.869

SECONDARY outcome

Timeframe: Week 4

Population: The full analysis set (FAS) for 4 weeks treatment period which is however restricted to patients with evaluable data for this endpoint - analysis with imputation

PEFR measurements were recorded by means of a patient diary on a daily basis. This diary was used to record the twice daily PEFs,

Evening measurements were performed at bedtime.The highest of three readings for each measurement were recorded.

Outcome measures

Measure	Placebo n=78 Participants Placebo	Olodaterol 2mcg n=83 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=78 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Weekly Mean Evening PEFR After 4 Weeks	227.39 Liter/minute Standard Error 4.085	256.44 Liter/minute Standard Error 3.955	258.34 Liter/minute Standard Error 4.083	264.58 Liter/minute Standard Error 3.890

SECONDARY outcome

Timeframe: Week 4

Population: The full analysis set (FAS) for 4 weeks treatment period which is however restricted to patients with evaluable data for this endpoint - analysis with imputation

Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol )

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=83 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks	0.778 Number of puffs Standard Error 0.110	0.587 Number of puffs Standard Error 0.107	0.324 Number of puffs Standard Error 0.109	0.392 Number of puffs Standard Error 0.105

SECONDARY outcome

Timeframe: 4 weeks

Population: Treated set.

Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical examination. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations).

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination Atrioventricular block second degree	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	1.2 percentage of participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination Blood lactate dehydrogenase increased	0.0 percentage of participants	0.0 percentage of participants	1.3 percentage of participants	0.0 percentage of participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination Blood glucose increased	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	1.2 percentage of participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination White blood cell count decreased	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	1.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Treated set.

Difference from baseline in Potassium (normalized values). Normalization means that the values from different laboratories are transformed in such a way that they are directly comparable.

Outcome measures

Measure	Placebo n=79 Participants Placebo	Olodaterol 2mcg n=84 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 Participants Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 Participants Olodaterol 10mcg inhalation solution via Respimat
Difference From Baseline in Potassium	0.0 mmol/L Standard Deviation 0.5	0.1 mmol/L Standard Deviation 0.6	-0.0 mmol/L Standard Deviation 0.5	0.1 mmol/L Standard Deviation 1.1

SECONDARY outcome

Timeframe: after first inhalated administration

Population: Treated set which is however restricted to patients with evaluable data for this endpoint (Patients in which all plasma concentration values were below limit of quantification (BLQ), were excluded from the analysis and were not included into the total number of participants affected for this outcome measure)

Cmax only calculated if >1/3 of the patients have available pharmacokinetic parameters,thus not applicable for the Olodaterol 2 mcg

Outcome measures

Measure	Placebo n=53 Participants Placebo	Olodaterol 2mcg n=81 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg Olodaterol 10mcg inhalation solution via Respimat
Cmax (Maximum Measured Concentration of the Analyte in Plasma)	4.17 pg/mL Geometric Coefficient of Variation 46.7	8.22 pg/mL Geometric Coefficient of Variation 58.3	—	—

SECONDARY outcome

Timeframe: visit at week 4

Population: Treated set which is however restricted to patients with evaluable data for this endpoint (Patients in which all plasma concentration values were below limit of quantification (BLQ), were excluded from the analysis and were not included into the total number of participants affected for this outcome measure)

Cmax,ss only calculated if >1/3 of the patients have available pharmacokinetic parameters, thus not applicable for the Olodaterol 2 mcg

Outcome measures

Measure	Placebo n=67 Participants Placebo	Olodaterol 2mcg n=78 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg Olodaterol 10mcg inhalation solution via Respimat
Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State)	5.92 pg/mL Geometric Coefficient of Variation 57.4	13.1 pg/mL Geometric Coefficient of Variation 58.6	—	—

SECONDARY outcome

Timeframe: after first inhalated administration

Population: Treated set which is however restricted to patients with evaluable data for this endpoint (Patients in which all plasma concentration values were below limit of quantification (BLQ), were excluded from the analysis and were not included into the total number of participants affected for this outcome measure)

Area under the concentration curve from 0 to 1 hour using trapezoid rule, only calculated if >1/3 of the patients have available pharmacokinetic parameters,thus not applicable for Olodaterol 2mcg group

Outcome measures

Measure	Placebo n=30 Participants Placebo	Olodaterol 2mcg n=77 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg Olodaterol 10mcg inhalation solution via Respimat
AUC0-1	3.67 pg*h/mL Geometric Coefficient of Variation 35.6	6.08 pg*h/mL Geometric Coefficient of Variation 50.8	—	—

SECONDARY outcome

Timeframe: visit at week 4

Population: Treated set which is however restricted to patients with evaluable data for this endpoint (Patients in which all plasma concentration values were below limit of quantification (BLQ), were excluded from the analysis and were not included into the total number of participants affected for this outcome measure)

Area under the concentration curve from 0 to 1 hour at steady state using trapezoid rule, only calculated if >1/3 of the patients have available pharmacokinetic parameters, thus not applicable for Olodaterol 2mcg group

Outcome measures

Measure	Placebo n=64 Participants Placebo	Olodaterol 2mcg n=77 Participants Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg Olodaterol 10mcg inhalation solution via Respimat
AUC0-1,ss	4.85 pg*h/mL Geometric Coefficient of Variation 54.6	10.8 pg*h/mL Geometric Coefficient of Variation 54.0	—	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Olodaterol 2mcg

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Olodaterol 5mcg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Olodaterol 10mcg

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=79 participants at risk Placebo	Olodaterol 2mcg n=84 participants at risk Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 participants at risk Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 participants at risk Olodaterol 10mcg inhalation solution via Respimat
Infections and infestations Influenza	1.3% 1/79 • 4 weeks	0.00% 0/84 • 4 weeks	0.00% 0/79 • 4 weeks	0.00% 0/86 • 4 weeks
Infections and infestations Herpes zoster	0.00% 0/79 • 4 weeks	0.00% 0/84 • 4 weeks	0.00% 0/79 • 4 weeks	1.2% 1/86 • 4 weeks
Eye disorders Cataract	0.00% 0/79 • 4 weeks	1.2% 1/84 • 4 weeks	0.00% 0/79 • 4 weeks	0.00% 0/86 • 4 weeks
Ear and labyrinth disorders Meniere's disease	0.00% 0/79 • 4 weeks	0.00% 0/84 • 4 weeks	0.00% 0/79 • 4 weeks	1.2% 1/86 • 4 weeks
Cardiac disorders Angina pectoris	0.00% 0/79 • 4 weeks	1.2% 1/84 • 4 weeks	0.00% 0/79 • 4 weeks	0.00% 0/86 • 4 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.3% 1/79 • 4 weeks	1.2% 1/84 • 4 weeks	1.3% 1/79 • 4 weeks	0.00% 0/86 • 4 weeks
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.3% 1/79 • 4 weeks	0.00% 0/84 • 4 weeks	0.00% 0/79 • 4 weeks	0.00% 0/86 • 4 weeks
Injury, poisoning and procedural complications Hand fracture	0.00% 0/79 • 4 weeks	0.00% 0/84 • 4 weeks	0.00% 0/79 • 4 weeks	1.2% 1/86 • 4 weeks

Other adverse events

Measure	Placebo n=79 participants at risk Placebo	Olodaterol 2mcg n=84 participants at risk Olodaterol 2mcg inhalation solution via Respimat	Olodaterol 5mcg n=79 participants at risk Olodaterol 5mcg inhalation solution via Respimat	Olodaterol 10mcg n=86 participants at risk Olodaterol 10mcg inhalation solution via Respimat
Infections and infestations Nasopharyngitis	3.8% 3/79 • 4 weeks	10.7% 9/84 • 4 weeks	3.8% 3/79 • 4 weeks	5.8% 5/86 • 4 weeks
Musculoskeletal and connective tissue disorders Myalgia	5.1% 4/79 • 4 weeks	0.00% 0/84 • 4 weeks	0.00% 0/79 • 4 weeks	0.00% 0/86 • 4 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place