12 / 48 Week Pivotal PFT vs PBO in COPD I

Randomised, Double-blind, 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 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Respimat® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This primary objective of this study is to compare two doses of BI 1744 CL inhalation solution delivered by the Respimat® inhaler once daily to placebo in patients with chronic obstructive pulmonary disease (COPD).

The safety of BI 1744 CL inhalation solution delivered through the Respimat inhaler will also be compared to placebo.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Olodaterol (BI1744); Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 625
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia
      • 1222.11.1143 Boehringer Ingelheim Investigational Site
    • Glebe, New South Wales, Australia
      • 1222.11.1145 Boehringer Ingelheim Investigational Site
    • Westmead, New South Wales, Australia
      • 1222.11.1144 Boehringer Ingelheim Investigational Site
  • South Australia
    • Toorak Gardens, South Australia, Australia
      • 1222.11.1142 Boehringer Ingelheim Investigational Site
    • Woodville, South Australia, Australia
      • 1222.11.1141 Boehringer Ingelheim Investigational Site
• China
  • Beijing, China
    • 1222.11.1166 Boehringer Ingelheim Investigational Site
  • Changsha, China
    • 1222.11.1171 Boehringer Ingelheim Investigational Site
  • Chengdu, China
    • 1222.11.1170 Boehringer Ingelheim Investigational Site
  • Chongqing, China
    • 1222.11.1169 Boehringer Ingelheim Investigational Site
  • Da lian, China
    • 1222.11.1172 Boehringer Ingelheim Investigational Site
  • Guangzhou, China
    • 1222.11.1163 Boehringer Ingelheim Investigational Site
  • Nanjing, China
    • 1222.11.1167 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1222.11.1164 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1222.11.1165 Boehringer Ingelheim Investigational Site
  • Shenyang, China
    • 1222.11.1173 Boehringer Ingelheim Investigational Site
  • Xi'An, China
    • 1222.11.1168 Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1222.11.1151 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1222.11.1156 Boehringer Ingelheim Investigational Site
  • Erfurt, Germany
    • 1222.11.1157 Boehringer Ingelheim Investigational Site
  • Halle, Germany
    • 1222.11.1154 Boehringer Ingelheim Investigational Site
  • Kassel, Germany
    • 1222.11.1153 Boehringer Ingelheim Investigational Site
  • Oschersleben, Germany
    • 1222.11.1158 Boehringer Ingelheim Investigational Site
  • Potsdam, Germany
    • 1222.11.1152 Boehringer Ingelheim Investigational Site
  • Weinheim, Germany
    • 1222.11.1155 Boehringer Ingelheim Investigational Site
• New Zealand
  • Hamilton, New Zealand
    • 1222.11.1138 Boehringer Ingelheim Investigational Site
  • Otahuhu, New Zealand
    • 1222.11.1139 Boehringer Ingelheim Investigational Site
  • Tauranga, New Zealand
    • 1222.11.1136 Boehringer Ingelheim Investigational Site
  • Wellington, New Zealand
    • 1222.11.1137 Boehringer Ingelheim Investigational Site
• Taiwan
  • Changhua, Taiwan
    • 1222.11.1180 Boehringer Ingelheim Investigational Site
  • Chia-Yi, Taiwan
    • 1222.11.1181 Boehringer Ingelheim Investigational Site
  • Taichung, Taiwan
    • 1222.11.1179 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 1222.11.1177 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 1222.11.1178 Boehringer Ingelheim Investigational Site
• United States
  • Alabama
    • Jasper, Alabama, United States
      • 1222.11.1122 Boehringer Ingelheim Investigational Site
  • California
    • Berkeley, California, United States
      • 1222.11.1116 Boehringer Ingelheim Investigational Site
    • Los Angeles, California, United States
      • 1222.11.1121 Boehringer Ingelheim Investigational Site
  • Colorado
    • Fort Collins, Colorado, United States
      • 1222.11.1111 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Stamford, Connecticut, United States
      • 1222.11.1117 Boehringer Ingelheim Investigational Site
  • Florida
    • Deland, Florida, United States
      • 1222.11.1110 Boehringer Ingelheim Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States
      • 1222.11.1106 Boehringer Ingelheim Investigational Site
  • Indiana
    • Evansville, Indiana, United States
      • 1222.11.1108 Boehringer Ingelheim Investigational Site
  • Kentucky
    • Bowling Green, Kentucky, United States
      • 1222.11.1109 Boehringer Ingelheim Investigational Site
  • Missouri
    • St. Louis, Missouri, United States
      • 1222.11.1113 Boehringer Ingelheim Investigational Site
  • New York
    • Larchmont, New York, United States
      • 1222.11.1115 Boehringer Ingelheim Investigational Site
  • Ohio
    • Toledo, Ohio, United States
      • 1222.11.1120 Boehringer Ingelheim Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • 1222.11.1105 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • 1222.11.1112 Boehringer Ingelheim Investigational Site
    • Greer, South Carolina, United States
      • 1222.11.1119 Boehringer Ingelheim Investigational Site
    • Union, South Carolina, United States
      • 1222.11.1102 Boehringer Ingelheim Investigational Site
  • Texas
    • Killeen, Texas, United States
      • 1222.11.1124 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 1222.11.1101 Boehringer Ingelheim Investigational Site
  • Washington
    • Spokane, Washington, United States
      • 1222.11.1103 Boehringer Ingelheim Investigational Site
    • Spokane, Washington, United States
      • 1222.11.1114 Boehringer Ingelheim Investigational Site
    • Tacoma, Washington, United States
      • 1222.11.1123 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• All patients must have a diagnosis of chronic obstructive pulmonary disease
• Male or female patients, 40 years of age or older Patients must be current or ex-smokers with a smoking history of more than 10 pack years Post bronchodilator FEV1 <80% predicted and post-bronchodilator FEV1/FVC <70%

Exclusion criteria:

• Patients with a significant disease other than COPD
• Patients with a history of asthma
• Patients with any of the following conditions:

a history of myocardial infarction within 1 year of screening visit (Visit 1) unstable or life-threatening cardiac arrhythmia. have been hospitalized for heart failure within the past year. known active tuberculosis a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed) a history of life-threatening pulmonary obstruction a history of cystic fibrosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olodaterol (BI 1744) High; High dose inhaled orally once daily from the Respimat inhaler	Drug: Olodaterol (BI1744); Comparison of low and high doses on efficacy and safety in COPD patients
Experimental: Olodaterol (BI 1744) Low; Low dose inhaled orally once daily from the Respimat inhaler	Drug: Olodaterol (BI1744); Comparison of low and high doses on efficacy and safety in COPD patients
Placebo Comparator: Placebo; Olodaterol (BI1744) placebo inhaled orally once daily from the Respimat inhaler	Drug: placebo; Olodaterol (BI1744) placebo inhaled orally once daily from the Respimat inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)	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.	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 Day 85
Trough FEV1 Response at Day 85 (12 Weeks)	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.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. 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.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks	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 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.	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 After 6 Weeks	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 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.	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks	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 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.	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks	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 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.	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
Trough FEV1 Response After 2 Weeks	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 a -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.	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 after 2 weeks
Trough FEV1 Response After 6 Weeks	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.	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 after 6 weeks
Trough FEV1 Response After 18 Weeks	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.	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 after 18 weeks
Trough FEV1 Response After 24 Weeks	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.	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 after 24 weeks
Trough FEV1 Response After 32 Weeks	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.	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 after 32 weeks
Trough FEV1 Response After 40 Weeks	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.	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 after 40 weeks
Trough FEV1 Response After 48 Weeks	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.	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 after 48 weeks
Peak FEV1 (0-3h) Response 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.	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	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.	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	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.	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	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.	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	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.	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 Hours (AUC 0-3h) Response At Day 1	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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 at Day 1
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.	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
Trough FVC Response After 2 Weeks	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 FVCs obtained 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.	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 after 2 weeks
Trough FVC Response After 6 Weeks	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 FVCs obtained 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.	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 after 6 weeks
Trough FVC Response After 12 Weeks	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 FVCs obtained 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.	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 after 12 weeks
Trough FVC Response After 18 Weeks	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 FVCs obtained 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.	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 after 18 weeks
Trough FVC Response After 24 Weeks	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 FVCs obtained 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.	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 after 24 weeks
Trough FVC Response After 32 Weeks	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 FVCs obtained 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.	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 after 32 weeks
Trough FVC Response After 40 Weeks	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 FVCs obtained 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.	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 after 40 weeks
Trough FVC Response After 48 Weeks	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 FVCs obtained 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.	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 after 48 weeks
FVC Peak (0-3h) Response After 2 Weeks	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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.	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
FVC Peak (0-3h) Response After 6 Weeks	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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.	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
FVC Peak (0-3h) Response After 12 Weeks	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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.	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
FVC Peak (0-3h) Response After 24 Weeks	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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.	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
FVC Peak (0-3h) Response After 48 Weeks	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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.	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 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. 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.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)	Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.	immediately upon arising (before drug administration) from Screening to week 48
Weekly Mean Evening Peak Expiratory Flow Rate (PEF)	Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.	at bedtime from Screening to week 48
Patient's Global Rating at Week 6	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.	Week 6 visit
Patient's Global Rating at Week 12	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.	Week 12 visit
Patient's Global Rating at Week 24	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.	Week 24 visit
Patient's Global Rating at Week 48	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.	Week 48 visit
Change From Baseline in Potassium	Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements.	Day 1 and at 12, 24 and 48 weeks
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1	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 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.	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 at day 1
Peak FEV1 (0-3h) Response At Day 1	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.	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 at Day 1
FVC Peak (0-3h) Response At Day 1	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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.	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 at Day 1
Weekly Mean Daytime Rescue Use	The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.	From Screening to week 48
Weekly Mean Nighttime Rescue Use	The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.	From Screening to week 48
Weekly Mean Daily (24h) Rescue Use	The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.	From Screening to week 48
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.	Baseline to end of study at 48 weeks.
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.	Baseline to end of study at 48 weeks.
Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.	Baseline to end of study at 48 weeks.
Number of COPD Exacerbations	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.	Baseline to end of study at week 48 visit
Number of COPD Exacerbations Requiring Hospitalization	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.	Baseline to end of study at week 48 visit
Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	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.	Baseline to end of study at 48 weeks.
Changes in Safety Parameters Related to Treatment	Occurrence of bronchoconstriction, cardiac disorders and investigations related to treatment. Bronchoconstriction is defined as any of the following events: Drop in trough FEV1 >= 15%, Rescue medication use within 30 min of inhaling randomized treatment on a clinic test day or Cough, wheeze, or dyspnoea AE within 30 min of inhaling randomized treatment on a clinic test day.	48 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Singh D, Wedzicha JA, Siddiqui S, de la Hoz A, Xue W, Magnussen H, Miravitlles M, Chalmers JD, Calverley PMA. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.
• Andreas S, Bothner U, de la Hoz A, Kloer I, Trampisch M, Alter P. A Post Hoc Holter ECG Analysis of Olodaterol and Formoterol in Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1955-1965. doi: 10.2147/COPD.S246353. eCollection 2020.
• Andreas S, Bothner U, Trampisch M, Haensel M, Buhl R, Alter P. Effect of long-acting beta2-agonists olodaterol and formoterol on heart rate and blood pressure in chronic obstructive pulmonary disease patients. Pulm Pharmacol Ther. 2018 Oct;52:1-6. doi: 10.1016/j.pupt.2018.08.002. Epub 2018 Aug 2.
• Ferguson GT, Feldman GJ, Hofbauer P, Hamilton A, Allen L, Korducki L, Sachs P. Efficacy and safety of olodaterol once daily delivered via Respimat(R) in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014 Jun 16;9:629-45. doi: 10.2147/COPD.S61717. eCollection 2014.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: October 29, 2008
• First Submitted That Met QC Criteria: October 29, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Estimate): June 9, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Olodaterol
• Other Study ID Numbers: 1222.11; 2008-003647-36 (EudraCT Number: EudraCT)