Trial Outcomes & Findings for BI 1744 CL With Respimat Once Daily Versus Twice Daily in COPD (NCT NCT00846768)

NCT ID: NCT00846768

Last Updated: 2014-07-01

Results Overview

Response was defined as change from baseline. Baseline FEV1 AUC (0-12) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 47 participants
• Primary outcome timeframe: Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose
• Results posted on: 2014-07-01

Participant Flow

This was a multi-centre, randomised, double-blind, 4-way crossover trial. The duration of each treatment period was 3 weeks with no washout period between treatments.

Participant milestones

Measure	Olo 2mcg Bid / Olo 10mcg qd / Olo 5mcg qd / Olo 5mcg Bid Patients were administered Olodaterol 2 mcg bid in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period and Olodaterol 5 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg qd / Olo 2mcg Bid / Olo 5mcg Bid / Olo 10mcg qd Patients were administered Olodaterol 5 mcg qd in the first period, Olodaterol 2 mcg bid in the second period, Olodaterol 5 mcg bid in the third period and Olodaterol 10 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg Bid / Olo 5mcg qd / Olo 10mcg qd / Olo 2mcg Bid Patients were administered Olodaterol 5 mcg bid in the first period, Olodaterol 5 mcg qd in the second period, Olodaterol 10 mcg qd in the third period and Olodaterol 2 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg qd / Olo 5mcg Bid / Olo 2mcg Bid / Olo 5mcg qd Patients were administered Olodaterol 10 mcg qd in the first period, Olodaterol 5 mcg bid in the second period, Olodaterol 2 mcg bid in the third period and Olodaterol 5 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler.
Overall Study STARTED	11	12	12	12
Overall Study COMPLETED	11	11	12	12
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Measure	Olo 2mcg Bid / Olo 10mcg qd / Olo 5mcg qd / Olo 5mcg Bid Patients were administered Olodaterol 2 mcg bid in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period and Olodaterol 5 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg qd / Olo 2mcg Bid / Olo 5mcg Bid / Olo 10mcg qd Patients were administered Olodaterol 5 mcg qd in the first period, Olodaterol 2 mcg bid in the second period, Olodaterol 5 mcg bid in the third period and Olodaterol 10 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler.	Olo 5mcg Bid / Olo 5mcg qd / Olo 10mcg qd / Olo 2mcg Bid Patients were administered Olodaterol 5 mcg bid in the first period, Olodaterol 5 mcg qd in the second period, Olodaterol 10 mcg qd in the third period and Olodaterol 2 mcg bid in the fourth period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg qd / Olo 5mcg Bid / Olo 2mcg Bid / Olo 5mcg qd Patients were administered Olodaterol 10 mcg qd in the first period, Olodaterol 5 mcg bid in the second period, Olodaterol 2 mcg bid in the third period and Olodaterol 5 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler.
Overall Study Adverse Event	0	1	0	0

Baseline Characteristics

BI 1744 CL With Respimat Once Daily Versus Twice Daily in COPD

Baseline characteristics by cohort

Measure	Study Total n=47 Participants Total number of patients treated in the study. This was a randomised, double-blind, active-controlled, 4 way crossover trial. 47 patients were assigned randomly to one of 4 treatment sequences in which they received each of the 4 treatments. The duration of each treatment period was 3 weeks with no washout period between treatments.
Age, Continuous	65.57 years STANDARD_DEVIATION 7.96 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Baseline FEV1 AUC (0-12) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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	Olo 2 mcg Bid n=46 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment	0.155 Liter Standard Error 0.024	0.209 Liter Standard Error 0.024	0.189 Liter Standard Error 0.024	0.204 Liter Standard Error 0.024

PRIMARY outcome

Timeframe: Day 0: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to planned evening dose on day 1; Day 21: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to evening dose

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Baseline FEV1 AUC (12-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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	Olo 2 mcg Bid n=46 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment	0.167 Liter Standard Error 0.022	0.155 Liter Standard Error 0.022	0.201 Liter Standard Error 0.022	0.149 Liter Standard Error 0.022

SECONDARY outcome

Timeframe: Day0:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to planned morning dose on day1,0:30,1,2,10,11,11:50h relative to planned evening dose on day1; Day21:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to morning dose,0:30,1,2,10,11,11:50h relative to evening dose

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Baseline FEV1 AUC (0-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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	Olo 2 mcg Bid n=46 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
FEV1 Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment	0.160 Liter Standard Error 0.022	0.182 Liter Standard Error 0.022	0.195 Liter Standard Error 0.022	0.176 Liter Standard Error 0.022

SECONDARY outcome

Timeframe: Baseline, 3 weeks

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the last dose after three weeks of treatment.

Outcome measures

Measure	Olo 2 mcg Bid n=45 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Peak FEV1 (0-3h) Response After 3 Weeks	0.187 Liter Standard Error 0.029	0.249 Liter Standard Error 0.029	0.230 Liter Standard Error 0.029	0.242 Liter Standard Error 0.029

SECONDARY outcome

Timeframe: Baseline, 3 weeks

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values prior to first dose of treatment. Trough values were the mean of values obtained 23h and 23 h 50 min after the last dose of study drug after three weeks of treatment .

Outcome measures

Measure	Olo 2 mcg Bid n=45 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Trough FEV1 Response	0.093 Liter Standard Error 0.028	0.108 Liter Standard Error 0.028	0.129 Liter Standard Error 0.028	0.087 Liter Standard Error 0.028

SECONDARY outcome

Timeframe: Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Baseline FVC AUC (0-12) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FVC 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	Olo 2 mcg Bid n=46 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
FVC Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment	0.262 Liter Standard Error 0.043	0.335 Liter Standard Error 0.043	0.294 Liter Standard Error 0.043	0.340 Liter Standard Error 0.043

SECONDARY outcome

Timeframe: Day 0: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to planned evening dose on day 1; Day 21: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to evening dose

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Baseline FVC AUC (12-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FVC 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	Olo 2 mcg Bid n=46 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
FVC Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment	0.239 Liter Standard Error 0.043	0.215 Liter Standard Error 0.043	0.318 Liter Standard Error 0.043	0.219 Liter Standard Error 0.043

SECONDARY outcome

Timeframe: Day0:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to planned morning dose on day1, 0:30,1,2,10,11,11:50h relative to planned evening dose on day1; Day21:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to morning dose,0:30,1,2,10,11,11:50h relative to evening dose

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Baseline FVC AUC (0-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FVC 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	Olo 2 mcg Bid n=46 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
FVC Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment	0.249 Liter Standard Error 0.041	0.275 Liter Standard Error 0.041	0.306 Liter Standard Error 0.041	0.279 Liter Standard Error 0.041

SECONDARY outcome

Timeframe: Baseline, 3 weeks

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after the last dose after three weeks of treatment.

Outcome measures

Measure	Olo 2 mcg Bid n=45 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Peak FVC (0-3h) Response After 3 Weeks	0.325 Liter Standard Error 0.049	0.417 Liter Standard Error 0.049	0.349 Liter Standard Error 0.049	0.433 Liter Standard Error 0.049

SECONDARY outcome

Timeframe: Baseline, 3 weeks

Population: Full analysis set (FAS). FAS is defined as all randomised and treated patients with baseline (pre-dose) data and evaluable post-dose data for at least one period.

Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values prior to first dose of treatment. Trough values were the mean of values obtained 23h and 23 h 50 min after the last dose of study drug after three weeks of treatment .

Outcome measures

Measure	Olo 2 mcg Bid n=45 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Trough FVC Response	0.111 Liter Standard Error 0.054	0.177 Liter Standard Error 0.054	0.181 Liter Standard Error 0.054	0.162 Liter Standard Error 0.054

SECONDARY outcome

Timeframe: 3 weeks

Population: Treated set.

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	Olo 2 mcg Bid n=47 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination Investigations	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination Cardiac disorders	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: 3 weeks

Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of PK parameters or had insufficient data. In the "Olo 2 mcg Bid" Arm, there were only 14 patients with values within the validated concentration range.

Steady state concentration of the analyte in plasma measured at 0.167 hours post dosing in week 3. The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters. Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range.

Outcome measures

Measure	Olo 2 mcg Bid Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=25 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=36 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=41 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Pharmacokinetics (PK): Concentration of the Analyte in Plasma Measured at 0.167 Hours Post Dosing at Steady State	—	3.52 pg/mL Geometric Coefficient of Variation 35.9	4.28 pg/mL Geometric Coefficient of Variation 42.0	5.78 pg/mL Geometric Coefficient of Variation 62.1

SECONDARY outcome

Timeframe: 3 weeks

Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of PK parameters or had insufficient data.

Amount of analyte that is eliminated in urine at steady state from the time point 0 hours to time point 12 hours after dosing in week 3 (after the morning dose for the bid dose regimens). The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters.

Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range.

Outcome measures

Measure	Olo 2 mcg Bid n=45 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 12 Hours	68.2 ng Geometric Coefficient of Variation 67.5	115 ng Geometric Coefficient of Variation 68.8	177 ng Geometric Coefficient of Variation 64.8	213 ng Geometric Coefficient of Variation 70.6

SECONDARY outcome

Timeframe: 3 weeks

Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of PK parameters or had insufficient data. This endpoint was only calculated for the two qd dose regimens, therefore the number of patients in the Olo 2 Mcg Bid Arm and the Olo 5 Mcg Bid Arm is 0.

Amount of analyte that is eliminated in urine at steady state from the time point 0 hours to time point 24 hours after dosing in week 3. The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters. Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range.

Outcome measures

Measure	Olo 2 mcg Bid Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=46 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 24 Hours	—	181 ng Geometric Coefficient of Variation 66.8	—	343 ng Geometric Coefficient of Variation 65.9

SECONDARY outcome

Timeframe: 3 weeks

Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of PK parameters or had insufficient data.

Fraction of analyte eliminated in urine at steady state from time point 0 hours to time point 12 hours after dosing in week 3 (after the morning dose for the bid dose regimens). The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters.

Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range.

Outcome measures

Measure	Olo 2 mcg Bid n=45 Participants Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 Participants Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 12 Hours	3.41 percent Geometric Coefficient of Variation 67.5	2.29 percent Geometric Coefficient of Variation 68.8	3.55 percent Geometric Coefficient of Variation 64.8	2.13 percent Geometric Coefficient of Variation 70.6

SECONDARY outcome

Timeframe: 3 weeks

Population: All evaluable subjects. A subject was considered to be not evaluable if the subject had a protocol violation relevant to the evaluation of PK parameters or had insufficient data. This endpoint was only calculated for the two qd dose regimens, therefore the number of patients in the Olo 2 Mcg Bid Arm and the Olo 5 Mcg Bid Arm is 0.

Fraction of analyte eliminated in urine at steady state from time point 0 hours to time point 24 hours after dosing in week 3. The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters. Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range.

Outcome measures

Measure	Olo 2 mcg Bid Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=46 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 24 Hours	—	3.61 percent Geometric Coefficient of Variation 66.8	—	3.43 percent Geometric Coefficient of Variation 65.9

Adverse Events

Olo 2 mcg Bid

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Olo 5 mcg qd

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Olo 5 mcg Bid

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Olo 10 mcg qd

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olo 2 mcg Bid n=47 participants at risk Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 participants at risk Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 participants at risk Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 participants at risk Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Infections and infestations Pneumonia	2.1% 1/47 • 3 weeks	0.00% 0/47 • 3 weeks	0.00% 0/46 • 3 weeks	0.00% 0/46 • 3 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.1% 1/47 • 3 weeks	0.00% 0/47 • 3 weeks	0.00% 0/46 • 3 weeks	0.00% 0/46 • 3 weeks

Other adverse events

Measure	Olo 2 mcg Bid n=47 participants at risk Olodaterol 2 mcg bid delivered by the Respimat Inhaler.	Olo 5 mcg qd n=47 participants at risk Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olo 5 mcg Bid n=46 participants at risk Olodaterol 5 mcg bid delivered by the Respimat Inhaler.	Olo 10 mcg qd n=46 participants at risk Olodaterol 10 mcg qd delivered by the Respimat Inhaler.
Infections and infestations Nasopharyngitis	2.1% 1/47 • 3 weeks	2.1% 1/47 • 3 weeks	6.5% 3/46 • 3 weeks	6.5% 3/46 • 3 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/47 • 3 weeks	6.4% 3/47 • 3 weeks	2.2% 1/46 • 3 weeks	0.00% 0/46 • 3 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 of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER