MedPath

Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease I

Phase 3
Completed
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
Registration Number
NCT00793624
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The primary objective of this study is to assess the long-term efficacy and safety of once daily treatment of BI 1744 CL inhalation solution (5 and 10 mcg) delivered via the Respimat® inhaler, in patients with COPD.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
906
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Olodaterol (BI 1744) LowOlodaterol (BI 1744)Low dose inhaled orally once daily from the Respimat inhaler
Olodaterol (BI 1744) HighOlodaterol (BI 1744)High dose inhaled orally once daily from the Respimat inhaler
PlaceboPlaceboOlodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler
Formoterol 12mcgFormoterol12mcg inhaled twice daily from the Aerolizer inhaler
Primary Outcome Measures
NameTimeMethod
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined AnalysisBaseline, Week 24

This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Mahler Transitional Dyspnea Index Focal Score at 24 WeeksBaseline, Week 24

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Trough FEV1 Response at Week 241 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Secondary Outcome Measures
NameTimeMethod
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6

Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12

Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 WeeksBaseline, Week 12

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).

Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 WeeksBaseline, Week 24

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).

Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 WeeksBaseline, Week 48

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).

Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined AnalysisBaseline, Week 24

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model.

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48

Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Trough FEV1 Response at Week 21 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FEV1 Response at Week 61 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FEV1 Response at Week 121 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FEV1 Response at Week 181 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FEV1 Response at Week 321 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FEV1 Response at Week 401 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FEV1 Response at Week 481 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FEV1 (0-3h) Response After 2 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FEV1 (0-3h) Response After 6 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FEV1 (0-3h) Response After 12 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks

Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FEV1 (0-3h) Response After 24 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks

Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FEV1 (0-3h) Response After 48 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks

Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12

Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Trough FVC Response at Week 61 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6

Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Trough FVC Response at Week 21 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Patient's Global Rating (PGR) at 12 WeeksWeek 12

Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).

Mahler Transitional Dyspnea Index Focal Score at 12 WeeksBaseline, Week 12

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Mahler Transitional Dyspnea Index Focal Score at 32 WeeksBaseline, Week 32

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Mahler Transitional Dyspnea Index Focal Score at 40 WeeksBaseline, Week 40

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Number of COPD Exacerbations Requiring HospitalizationBaseline to end of study at week 48 visit

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization.

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48

Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. 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 litres.

Patient's Global Rating (PGR) at 24 WeeksWeek 24

Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).

Trough FVC Response at Week 121 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FVC Response at Week 181 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FVC Response at Week 241 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FVC Response at Week 321 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FVC Response at Week 481 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Trough FVC Response at Week 401 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FVC (0-3h) Response After 2 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FVC (0-3h) Response After 6 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FVC (0-3h) Response After 24 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks

Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak FVC (0-3h) Response After 48 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks

Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Peak Expiratory Flow Rate (PEFR) at Week 24Week 24

Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline.

Use of Rescue Medication at Week 24Week 24

Mean number of puffs of rescue medication used per day (daytime/nighttime/total)

Patient's Global Rating (PGR) at 6 WeeksWeek 6

Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).

Peak FVC (0-3h) Response After 12 Weeks1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks

Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Patient's Global Rating (PGR) at 48 WeeksWeek 48

Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).

Time to First Chronic Obstructive Pulmonary Disease (COPD) ExacerbationBaseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.

Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to HospitalizationBaseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.

Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) ExacerbationBaseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.

Number of COPD ExacerbationsBaseline to end of study at week 48 visit

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria.

Mahler Transitional Dyspnea Index Focal Score at 6 WeeksBaseline, Week 6

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Mahler Transitional Dyspnea Index Focal Score at 18 WeeksBaseline, Week 18

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Changes in Safety Parameters Related to Treatment48 weeks

Occurence of cardiac disorders and investigations related to treatment.

Mahler Transitional Dyspnea Index Focal Score at 48 WeeksBaseline, Week 48

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) ExacerbationsBaseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids.

Absolute Plasma Concentrationswithin 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18

Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.

Trial Locations

Locations (93)

1222.13.2101 Boehringer Ingelheim Investigational Site

🇫🇮

Tampere, Finland

1222.13.3102 Boehringer Ingelheim Investigational Site

🇲🇾

Kuala Lumpur, Malaysia

1222.13.2102 Boehringer Ingelheim Investigational Site

🇫🇮

Turku, Finland

1222.13.3202 Boehringer Ingelheim Investigational Site

🇵🇭

Quezon City, Philippines

1222.13.3402 Boehringer Ingelheim Investigational Site

🇨🇿

Tabor, Czech Republic

1222.13.2806 Boehringer Ingelheim Investigational Site

🇮🇳

Coimbatore-, India

1222.13.2103 Boehringer Ingelheim Investigational Site

🇫🇮

Lahti, Finland

1222.13.3104 Boehringer Ingelheim Investigational Site

🇲🇾

Kuantan, Malaysia

1222.13.3203 Boehringer Ingelheim Investigational Site

🇵🇭

Cebu, Philippines

1222.13.3303 Boehringer Ingelheim Investigational Site

🇹🇭

Bangkok, Thailand

1222.13.1407 Boehringer Ingelheim Investigational Site

🇨🇦

Chilliwack, British Columbia, Canada

1222.13.3403 Boehringer Ingelheim Investigational Site

🇨🇿

Cesky Tesin, Czech Republic

1222.13.3301 Boehringer Ingelheim Investigational Site

🇹🇭

Chiang Mai, Thailand

1222.13.3101 Boehringer Ingelheim Investigational Site

🇲🇾

Kota Kinabalu, Malaysia

1222.13.3201 Boehringer Ingelheim Investigational Site

🇵🇭

Quezon City, Philippines

1222.13.1404 Boehringer Ingelheim Investigational Site

🇨🇦

La Malbaie, Quebec, Canada

1222.13.2404 Boehringer Ingelheim Investigational Site

🇦🇷

Monte Grande, Argentina

1222.13.2501 Boehringer Ingelheim Investigational Site

🇧🇷

Sao Paulo, Brazil

1222.13.2403 Boehringer Ingelheim Investigational Site

🇦🇷

Capital Federal, Argentina

1222.13.2504 Boehringer Ingelheim Investigational Site

🇧🇷

Sao Paulo, Brazil

1222.13.1403 Boehringer Ingelheim Investigational Site

🇨🇦

Downsview, Ontario, Canada

1222.13.1408 Boehringer Ingelheim Investigational Site

🇨🇦

Calgary, Alberta, Canada

1222.13.3503 Boehringer Ingelheim Investigational Site

🇭🇷

Rijeka, Croatia

1222.13.2401 Boehringer Ingelheim Investigational Site

🇦🇷

Capital Federal, Argentina

1222.13.1412 Boehringer Ingelheim Investigational Site

🇨🇦

Hamilton, Ontario, Canada

1222.13.1401 Boehringer Ingelheim Investigational Site

🇨🇦

Niagara Falls, Ontario, Canada

1222.13.2402 Boehringer Ingelheim Investigational Site

🇦🇷

Mar del Plata, Argentina

1222.13.1402 Boehringer Ingelheim Investigational Site

🇨🇦

Saskatoon, Saskatchewan, Canada

1222.13.3504 Boehringer Ingelheim Investigational Site

🇭🇷

Split, Croatia

1222.13.1506 Boehringer Ingelheim Investigational Site

🇩🇪

Berlin, Germany

1222.13.1505 Boehringer Ingelheim Investigational Site

🇩🇪

Reinfeld, Germany

1222.13.1503 Boehringer Ingelheim Investigational Site

🇩🇪

Berlin, Germany

1222.13.1511 Boehringer Ingelheim Investigational Site

🇩🇪

Dortmund, Germany

1222.13.2804 Boehringer Ingelheim Investigational Site

🇮🇳

Bangalore, India

1222.13.2803 Boehringer Ingelheim Investigational Site

🇮🇳

Chennai, India

1222.13.1512 Boehringer Ingelheim Investigational Site

🇩🇪

Kiel, Germany

1222.13.2801 Boehringer Ingelheim Investigational Site

🇮🇳

Indore, India

1222.13.2802 Boehringer Ingelheim Investigational Site

🇮🇳

Ludhiana, Punjab, India

1222.13.2812 Boehringer Ingelheim Investigational Site

🇮🇳

Mumbai, India

1222.13.1704 Boehringer Ingelheim Investigational Site

🇮🇹

Catania, Italy

1222.13.1701 Boehringer Ingelheim Investigational Site

🇮🇹

Pisa, Italy

1222.13.2302 Boehringer Ingelheim Investigational Site

🇿🇦

Durban, South Africa

1222.13.1804 Boehringer Ingelheim Investigational Site

🇪🇸

Pozuelo de Alarcón, Spain

1222.13.1802 Boehringer Ingelheim Investigational Site

🇪🇸

Els Hostalets de Balenyà, Spain

1222.13.1806 Boehringer Ingelheim Investigational Site

🇪🇸

Elda, Spain

1222.13.2810 Boehringer Ingelheim Investigational Site

🇮🇳

Hyderabad, India

1222.13.2706 Boehringer Ingelheim Investigational Site

🇰🇷

Seoul, Korea, Republic of

1222.13.2301 Boehringer Ingelheim Investigational Site

🇿🇦

Pretoria, South Africa

1222.13.2809 Boehringer Ingelheim Investigational Site

🇮🇳

Mumbai, India

1222.13.2811 Boehringer Ingelheim Investigational Site

🇮🇳

Pune, India

1222.13.3603 Boehringer Ingelheim Investigational Site

🇺🇦

Kiev, Ukraine

1222.13.2701 Boehringer Ingelheim Investigational Site

🇰🇷

Gwangju, Korea, Republic of

1222.13.1902 Boehringer Ingelheim Investigational Site

🇸🇪

Sundsvall, Sweden

1222.13.2703 Boehringer Ingelheim Investigational Site

🇰🇷

Seoul, Korea, Republic of

1222.13.2807 Boehringer Ingelheim Investigational Site

🇮🇳

Indore, India

1222.13.2805 Boehringer Ingelheim Investigational Site

🇮🇳

Jaipur, India

1222.13.3103 Boehringer Ingelheim Investigational Site

🇲🇾

Batu Caves, Malaysia

1222.13.2201 Boehringer Ingelheim Investigational Site

🇳🇴

Bergen, Norway

1222.13.2202 Boehringer Ingelheim Investigational Site

🇳🇴

Oslo, Norway

1222.13.3302 Boehringer Ingelheim Investigational Site

🇹🇭

Bangkok, Thailand

1222.13.3601 Boehringer Ingelheim Investigational Site

🇺🇦

Kharkiv, Ukraine

1222.13.2705 Boehringer Ingelheim Investigational Site

🇰🇷

Seoul, Korea, Republic of

1222.13.1703 Boehringer Ingelheim Investigational Site

🇮🇹

Trieste, Italy

1222.13.2702 Boehringer Ingelheim Investigational Site

🇰🇷

Incheon, Korea, Republic of

1222.13.1702 Boehringer Ingelheim Investigational Site

🇮🇹

Genova, Italy

1222.13.1901 Boehringer Ingelheim Investigational Site

🇸🇪

Boden, Sweden

1222.13.3602 Boehringer Ingelheim Investigational Site

🇺🇦

Ivano-Frankivsk, Ukraine

1222.13.1705 Boehringer Ingelheim Investigational Site

🇮🇹

Siena, Italy

1222.13.1410 Boehringer Ingelheim Investigational Site

🇨🇦

Sarnia, Ontario, Canada

1222.13.1413 Boehringer Ingelheim Investigational Site

🇨🇦

Toronto, Ontario, Canada

1222.13.1411 Boehringer Ingelheim Investigational Site

🇨🇦

Montreal, Quebec, Canada

1222.13.1406 Boehringer Ingelheim Investigational Site

🇨🇦

Point Claire, Quebec, Canada

1222.13.2502 Boehringer Ingelheim Investigational Site

🇧🇷

Juiz de Fora, Brazil

1222.13.2505 Boehringer Ingelheim Investigational Site

🇧🇷

Rio de Janeiro, Brazil

1222.13.1805 Boehringer Ingelheim Investigational Site

🇪🇸

Valladolid, Spain

1222.13.1801 Boehringer Ingelheim Investigational Site

🇪🇸

Vic (Barcelona), Spain

1222.13.1514 Boehringer Ingelheim Investigational Site

🇩🇪

Essen, Germany

1222.13.1501 Boehringer Ingelheim Investigational Site

🇩🇪

Köln, Germany

1222.13.1507 Boehringer Ingelheim Investigational Site

🇩🇪

Schwerin, Germany

1222.13.2503 Boehringer Ingelheim Investigational Site

🇧🇷

Rio de Janeiro, Brazil

1222.13.2003 Boehringer Ingelheim Investigational Site

🇩🇰

Aalborg, Denmark

1222.13.3401 Boehringer Ingelheim Investigational Site

🇨🇿

Beroun, Czech Republic

1222.13.3502 Boehringer Ingelheim Investigational Site

🇭🇷

Dubrovnik, Croatia

1222.13.2002 Boehringer Ingelheim Investigational Site

🇩🇰

Hvidovre, Denmark

1222.13.2001 Boehringer Ingelheim Investigational Site

🇩🇰

Silkeborg, Denmark

1222.13.1502 Boehringer Ingelheim Investigational Site

🇩🇪

Berlin, Germany

1222.13.1509 Boehringer Ingelheim Investigational Site

🇩🇪

Großhansdorf, Germany

1222.13.1510 Boehringer Ingelheim Investigational Site

🇩🇪

Hannover, Germany

1222.13.1508 Boehringer Ingelheim Investigational Site

🇩🇪

Hannover, Germany

1222.13.2704 Boehringer Ingelheim Investigational Site

🇰🇷

Suwon, Korea, Republic of

1222.13.1803 Boehringer Ingelheim Investigational Site

🇪🇸

Aranjuez, Spain

1222.13.3501 Boehringer Ingelheim Investigational Site

🇭🇷

Zagreb, Croatia

1222.13.2901 Boehringer Ingelheim Investigational Site

🇭🇰

Kowloon, Hong Kong

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