Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.
Trough FEV1 (forced expiratory volume in 1 second) was defined as the mean of the 2 FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 15.
Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment
Trough FVC (forced vital capacity) was defined as the mean of the 2 FVC values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FVC response was defined as the change from baseline in trough FVC. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Response is defined as change from the baseline value. AUC(0-3h) (area under the curve) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.
FVC (forced vital capacity) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.
PEF (peak expiratory flow rate L/min) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) will be calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment
FEV1 (forced expiratory volume in 1 second) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment
FVC (forced vital capacity) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment
PEF (peak expiratory flow rate L/min) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
FEV1 (forced expiratory volume in 1 second) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
FVC (forced vital capacity) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
PEF (peak expiratory flow rate L/min) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
FEV1 and PEF (Unsupervised) AUC(0-6h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
AUC(0-6h) for FEV1, and PEF (unsupervised) were not studied because the pertinent information from the unsupervised pulmonary function tests was for the time interval from 9 to 12 hours post-dosing.
FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment
FEV1 (forced expiratory volume in 1 second) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment
PEF (peak expiratory flow rate L/min) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Weekly Mean Pre-dose Morning PEF [L/Min]
The patient will record twice daily peak flow measurements using an Asthma Monitor®Am2+ (AM2+) device. Morning measurements will be performed immediately upon arising after the patient has cleared out mucus, prior to administration of trial and/or rescue medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Weekly Mean Evening PEF [L/Min]
The patient will record twice daily peak flow measurements using an AM2+ device. The evening measurement will be performed at bedtime.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day
The means are adjusted, Based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Physician's Global Evaluation
Measured a 8-point scale, from 1 (poor) to 8 (excellent), as judged by the physician, over 4 weeks of treatment.
The physician made a global evaluation at the end of the Baseline Period (Test Day 1) and at each visit thereafter. These assessments were made prior to pulmonary function testing and reflected the physician's opinion of the patient's overall clinical condition. This evaluation was based on the need for concomitant medication, number and severity of COPD exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, and other relevant clinical observations.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Patient's Global Rating
Patient's Global Rating at the end of the 4 week treatment period.
Patients rated their health (respiratory condition) at Day 29 (compared to the day before they commenced treatment with study medication) on a 7-point scale as "very much better (1), much better (2), a little better (3), no change (4), a little worse (5), much worse (6), or very much worse (7)". The assessment was made prior to pulmonary function testing and all other study procedures. The Patient's Global Rating was also completed before the Physician's Global Evaluation.
The means are adjusted, based on an ANCOVA with terms for treatment, centre (centre random, treatment effect fixed).
Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities
Possible clinically significant anormalities (laboratory data); marked changes from baseline for vital signs, notable change in ECG and new onset of ECG abnormalities. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AEs).
All AEs with an onset after the first dose of study medication up to 21 days after the last dose of study medication were to have been assigned to the Treatment Period.
Cmax,ss Olodaterol [pg/mL]
Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss) after 4 weeks of treatment.
No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
Tmax,ss Olodaterol [h]
Time from last dosing to maximum concentration of Olodaterol in plasma at steady state (tmax,ss) after 4 weeks treatment.
No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
AUC(0-1h,ss) Olodaterol [pg*h/mL]
Area under the concentration-time curve of Olodaterol in plasma at steady state (AUC(0-1h,ss)) from 0 to 1 hour post dosing after 4 weeks of treatment.
No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
Cmax,ss Tiotropium [pg/mL]
Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss) after 4 weeks treatment.
Tmax,ss Tiotropium [h]
Time from last dosing to maximum concentration of Tiotropium in plasma at steady state (tmax,ss) after 4 weeks of treatment.
AUC(0-3h,ss) Tiotropium [pg*h/mL]
Area under the concentration-time curve of Tiotropium at steady state (AUC(0-3h,ss)) from 0 to 3 hours post dosing after 4 weeks of treatment.