Trial Outcomes & Findings for Characterisation of 24-hour FEV1-time Profiles of Inhaled BI 1744 CL and Inhaled Foradil in Patients With Chronic Obstructive Pulmonary Disease (NCT NCT00932646)

NCT ID: NCT00932646

Last Updated: 2016-02-05

Results Overview

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 100 participants
• Primary outcome timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
• Results posted on: 2016-02-05

Participant Flow

This was a randomised, double-blind, double dummy, placebo- and active-controlled, 4 way crossover trial. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.

Participant milestones

Measure	Placebo / Olo 5mcg / Olo 10mcg / Foradil 12mcg Patients were administered placebo in the first period, Olodaterol 5 mcg qd in the second period, Olodaterol 10 mcg qd in the third period and Foradil 12 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.	Olo 5mcg / Foradil 12mcg / Placebo / Olo 10mcg Patients were administered Olodaterol 5mcg qd in the first period, Foradil 12 mcg bid in the second period, placebo in the third period and Olodaterol 10 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.	Olo 10mcg / Placebo / Foradil 12mcg / Olo 5mcg Patients were administered Olodaterol 10 mcg qd in the first period, placebo in the second period, Foradil 12 mcg bid in the third period and Olodaterol 5 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.	Foradil 12mcg / Olo 10mcg / Olo 5mcg / Placebo Patients were administered Foradil 12 mcg bid in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period and placebo in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.
Overall Study STARTED	25	25	25	25
Overall Study COMPLETED	20	22	21	24
Overall Study NOT COMPLETED	5	3	4	1

Reasons for withdrawal

Measure	Placebo / Olo 5mcg / Olo 10mcg / Foradil 12mcg Patients were administered placebo in the first period, Olodaterol 5 mcg qd in the second period, Olodaterol 10 mcg qd in the third period and Foradil 12 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.	Olo 5mcg / Foradil 12mcg / Placebo / Olo 10mcg Patients were administered Olodaterol 5mcg qd in the first period, Foradil 12 mcg bid in the second period, placebo in the third period and Olodaterol 10 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.	Olo 10mcg / Placebo / Foradil 12mcg / Olo 5mcg Patients were administered Olodaterol 10 mcg qd in the first period, placebo in the second period, Foradil 12 mcg bid in the third period and Olodaterol 5 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.	Foradil 12mcg / Olo 10mcg / Olo 5mcg / Placebo Patients were administered Foradil 12 mcg bid in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period and placebo in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.
Overall Study Adverse Event	2	1	1	1
Overall Study Lost to Follow-up	2	1	0	0
Overall Study Withdrawal by Subject	1	1	3	0

Baseline Characteristics

Characterisation of 24-hour FEV1-time Profiles of Inhaled BI 1744 CL and Inhaled Foradil in Patients With Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Measure	Study Total n=100 Participants Total number of patients treated in the study. This was a randomised, double-blind, double dummy, placebo- and active-controlled, 4 way crossover trial. 99 patients were assigned randomly to one of 4 treatment sequences in which they received each of 4 treatments, two doses (5 microgram (mcg) or 10 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo delivered by Respimat Inhaler or Aerolizer Inhaler. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.
Age, Continuous	63.5 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment

Population: Full analysis set (FAS). FAS is defined as all patients with the baseline (pre-dose) date and any evaluable post-dosing data for the first co-primary endpoint FEV1AUC 0-12h.

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment	-0.022 Liter Standard Error 0.024	0.150 Liter Standard Error 0.024	0.152 Liter Standard Error 0.024	0.136 Liter Standard Error 0.024

PRIMARY outcome

Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

Population: Full analysis set (FAS).

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment	-0.048 Liter Standard Error 0.025	0.069 Liter Standard Error 0.025	0.072 Liter Standard Error 0.025	0.107 Liter Standard Error 0.025

SECONDARY outcome

Timeframe: 1 h and 10 min prior to am dose on the first day of the treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.

Population: FAS

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

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment	-0.035 Liter Standard Error 0.024	0.110 Liter Standard Error 0.024	0.112 Liter Standard Error 0.024	0.121 Liter Standard Error 0.024

SECONDARY outcome

Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to am dose after six weeks of treatment

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment	0.004 Liter Standard Error 0.024	0.190 Liter Standard Error 0.025	0.202 Liter Standard Error 0.025	0.217 Liter Standard Error 0.025

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak FEV1 (0-3h) Response	0.076 Liter Standard Error 0.026	0.268 Liter Standard Error 0.026	0.273 Liter Standard Error 0.026	0.293 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Trough FEV1 Response	0.012 Liter Standard Error 0.030	0.109 Liter Standard Error 0.030	0.115 Liter Standard Error 0.030	0.093 Liter Standard Error 0.030

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment

Population: FAS

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

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response	-0.032 Liter Standard Error 0.040	0.219 Liter Standard Error 0.040	0.214 Liter Standard Error 0.040	0.203 Liter Standard Error 0.040

SECONDARY outcome

Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

Population: FAS

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

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response	-0.078 Liter Standard Error 0.041	0.083 Liter Standard Error 0.041	0.079 Liter Standard Error 0.041	0.144 Liter Standard Error 0.041

SECONDARY outcome

Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.

Population: FAS

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

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response	-0.055 Liter Standard Error 0.039	0.151 Liter Standard Error 0.039	0.147 Liter Standard Error 0.039	0.174 Liter Standard Error 0.039

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Peak FVC (0-3h) Response	0.138 Liter Standard Error 0.043	0.436 Liter Standard Error 0.043	0.440 Liter Standard Error 0.043	0.475 Liter Standard Error 0.043

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: FAS

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

Outcome measures

Measure	Placebo n=91 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=92 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=90 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=90 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Trough FVC Response	-0.007 Liter Standard Error 0.053	0.125 Liter Standard Error 0.053	0.133 Liter Standard Error 0.054	0.141 Liter Standard Error 0.054

SECONDARY outcome

Timeframe: 6 weeks

Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. 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=94 Participants Matching Placebo delivered by the Respimat Inhaler or Aerolizer Inhaler.	Olo 5 mcg qd n=93 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=95 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Bid n=93 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Tachycardia	0 participants	0 participants	0 participants	1 participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG ECG QT prolonged	0 participants	0 participants	1 participants	0 participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Bundle branch block right	0 participants	0 participants	1 participants	0 participants

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Olo 5 mcg

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

Olo 10 mcg

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Form 12 mcg

Serious events: 5 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=94 participants at risk Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.	Olo 5 mcg n=93 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=95 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=93 participants at risk Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/94 • 6 weeks	1.1% 1/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Cardiac disorders Cardiac failure congestive	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	1.1% 1/95 • 6 weeks	0.00% 0/93 • 6 weeks
Cardiac disorders Coronary artery disease	0.00% 0/94 • 6 weeks	1.1% 1/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Cardiac disorders Ventricular fibrillation	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	1.1% 1/95 • 6 weeks	0.00% 0/93 • 6 weeks
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/94 • 6 weeks	1.1% 1/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Infections and infestations Lung infection pseudomonal	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	1.1% 1/93 • 6 weeks
Injury, poisoning and procedural complications Fall	1.1% 1/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Injury, poisoning and procedural complications Fractured sacrum	1.1% 1/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Injury, poisoning and procedural complications Pelvic fracture	1.1% 1/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.1% 1/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/94 • 6 weeks	1.1% 1/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Nervous system disorders Cerebrovascular accident	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	1.1% 1/93 • 6 weeks
Nervous system disorders Migraine	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	1.1% 1/93 • 6 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.1% 1/94 • 6 weeks	0.00% 0/93 • 6 weeks	1.1% 1/95 • 6 weeks	3.2% 3/93 • 6 weeks
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/94 • 6 weeks	1.1% 1/93 • 6 weeks	0.00% 0/95 • 6 weeks	0.00% 0/93 • 6 weeks
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	1.1% 1/95 • 6 weeks	0.00% 0/93 • 6 weeks
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/94 • 6 weeks	0.00% 0/93 • 6 weeks	0.00% 0/95 • 6 weeks	1.1% 1/93 • 6 weeks

Other adverse events

Measure	Placebo n=94 participants at risk Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.	Olo 5 mcg n=93 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=95 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=93 participants at risk Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Infections and infestations Upper respiratory tract infection	4.3% 4/94 • 6 weeks	4.3% 4/93 • 6 weeks	5.3% 5/95 • 6 weeks	5.4% 5/93 • 6 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	5.3% 5/94 • 6 weeks	5.4% 5/93 • 6 weeks	7.4% 7/95 • 6 weeks	2.2% 2/93 • 6 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 Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication
• Publication restrictions are in place

Restriction type: OTHER