A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 ug] and 10 ug [2 Actuations of 5 ug]) Delivered by the Respimat® Inhaler, and 48 Weeks of Twice Daily Foradil® (12 µg) Delivered by the Aerolizer® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 937
- Locations
- 98
- Primary Endpoint
- Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Olodaterol (BI 1744) Low
Low dose inhaled orally once daily from the Respimat inhaler
Intervention: Olodaterol (BI 1744) (Drug)
Olodaterol (BI 1744) High
High dose inhaled orally once daily from the Respimat inhaler
Intervention: Olodaterol (BI 1744) (Drug)
Formoterol 12mcg
12mcg inhaled twice daily from the Aerolizer inhaler
Intervention: Formoterol (Drug)
Placebo
Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
Time Frame: Baseline, 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).
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Time Frame: 1 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.
Trough FEV1 Response at Week 24
Time Frame: 1 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.
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
Time Frame: Baseline, 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).
Secondary Outcomes
- Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks(1 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)
- Trough FEV1 Response at Week 12(1 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.)
- Trough FEV1 Response at Week 18(1 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.)
- Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis(Baseline, Week 24)
- Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks(1 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)
- Trough FEV1 Response at Week 6(1 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.)
- Trough FVC Response at Week 48(1 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.)
- Peak FVC (0-3h) Response After 12 Weeks(1 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)
- Patient's Global Rating (PGR) at 12 Weeks(Week 12)
- Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks(Baseline, Week 24)
- Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks(Baseline, Week 12)
- Trough FVC Response at Week 12(1 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.)
- Trough FVC Response at Week 18(1 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.)
- Peak FVC (0-3h) Response After 2 Weeks(1 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)
- Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks(1 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)
- Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks(1 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)
- Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks(Baseline, Week 48)
- Trough FEV1 Response at Week 2(1 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.)
- Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks(1 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)
- Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks(1 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)
- Trough FEV1 Response at Week 32(1 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.)
- Trough FEV1 Response at Week 40(1 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.)
- Trough FEV1 Response at Week 48(1 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.)
- Peak FEV1 (0-3h) Response After 2 Weeks(1 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)
- Peak FEV1 (0-3h) Response After 6 Weeks(1 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)
- Peak FEV1 (0-3h) Response After 12 Weeks(1 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)
- Peak FEV1 (0-3h) Response After 24 Weeks(1 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)
- Peak FEV1 (0-3h) Response After 48 Weeks(1 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)
- Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks(1 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)
- Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks(1 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)
- Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks(1 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)
- Trough FVC Response at Week 2(1 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.)
- Mahler Transitional Dyspnea Index Focal Score at 18 Weeks(Baseline, Week 18)
- Mahler Transitional Dyspnea Index Focal Score at 32 Weeks(Baseline, Week 32)
- Trough FVC Response at Week 6(1 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.)
- Trough FVC Response at Week 24(1 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.)
- Trough FVC Response at Week 32(1 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.)
- Trough FVC Response at Week 40(1 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.)
- Peak FVC (0-3h) Response After 6 Weeks(1 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)
- Peak FVC (0-3h) Response After 48 Weeks(1 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)
- Peak Expiratory Flow Rate (PEFR) at Week 24(Week 24)
- Use of Rescue Medication at Week 24(Week 24)
- Mahler Transitional Dyspnea Index Focal Score at 6 Weeks(Baseline, Week 6)
- Peak FVC (0-3h) Response After 24 Weeks(1 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)
- Patient's Global Rating (PGR) at 6 Weeks(Week 6)
- Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization(Baseline to end of study at 48 weeks.)
- Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation(Baseline to end of study at 48 weeks.)
- Patient's Global Rating (PGR) at 24 Weeks(Week 24)
- Patient's Global Rating (PGR) at 48 Weeks(Week 48)
- Mahler Transitional Dyspnea Index Focal Score at 12 Weeks(Baseline, Week 12)
- Mahler Transitional Dyspnea Index Focal Score at 40 Weeks(Baseline, Week 40)
- Mahler Transitional Dyspnea Index Focal Score at 48 Weeks(Baseline, Week 48)
- Number of COPD Exacerbations Requiring Hospitalization(Baseline to end of study at week 48 visit)
- Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation(Baseline to end of study at 48 weeks.)
- Number of COPD Exacerbations(Baseline to end of study at week 48 visit)
- Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations(Baseline to end of study at 48 weeks.)
- Changes in Safety Parameters Related to Treatment(48 weeks)
- Absolute Plasma Concentrations(within 2 hours before first study drug administration and 10 minutes post-dose at week 6, 12 and 18)