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

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)

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 Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Olodaterol (BI 1744); Drug: Formoterol; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 906
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal, Argentina
    • 1222.13.2401 Boehringer Ingelheim Investigational Site
  • Capital Federal, Argentina
    • 1222.13.2403 Boehringer Ingelheim Investigational Site
  • Mar del Plata, Argentina
    • 1222.13.2402 Boehringer Ingelheim Investigational Site
  • Monte Grande, Argentina
    • 1222.13.2404 Boehringer Ingelheim Investigational Site
• Brazil
  • Juiz de Fora, Brazil
    • 1222.13.2502 Boehringer Ingelheim Investigational Site
  • Rio de Janeiro, Brazil
    • 1222.13.2503 Boehringer Ingelheim Investigational Site
  • Rio de Janeiro, Brazil
    • 1222.13.2505 Boehringer Ingelheim Investigational Site
  • Sao Paulo, Brazil
    • 1222.13.2501 Boehringer Ingelheim Investigational Site
  • Sao Paulo, Brazil
    • 1222.13.2504 Boehringer Ingelheim Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • 1222.13.1408 Boehringer Ingelheim Investigational Site
  • British Columbia
    • Chilliwack, British Columbia, Canada
      • 1222.13.1407 Boehringer Ingelheim Investigational Site
  • Ontario
    • Downsview, Ontario, Canada
      • 1222.13.1403 Boehringer Ingelheim Investigational Site
    • Hamilton, Ontario, Canada
      • 1222.13.1412 Boehringer Ingelheim Investigational Site
    • Niagara Falls, Ontario, Canada
      • 1222.13.1401 Boehringer Ingelheim Investigational Site
    • Sarnia, Ontario, Canada
      • 1222.13.1410 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1222.13.1413 Boehringer Ingelheim Investigational Site
  • Quebec
    • La Malbaie, Quebec, Canada
      • 1222.13.1404 Boehringer Ingelheim Investigational Site
    • Montreal, Quebec, Canada
      • 1222.13.1411 Boehringer Ingelheim Investigational Site
    • Point Claire, Quebec, Canada
      • 1222.13.1406 Boehringer Ingelheim Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 1222.13.1402 Boehringer Ingelheim Investigational Site
• Croatia
  • Dubrovnik, Croatia
    • 1222.13.3502 Boehringer Ingelheim Investigational Site
  • Rijeka, Croatia
    • 1222.13.3503 Boehringer Ingelheim Investigational Site
  • Split, Croatia
    • 1222.13.3504 Boehringer Ingelheim Investigational Site
  • Zagreb, Croatia
    • 1222.13.3501 Boehringer Ingelheim Investigational Site
• Czech Republic
  • Beroun, Czech Republic
    • 1222.13.3401 Boehringer Ingelheim Investigational Site
  • Cesky Tesin, Czech Republic
    • 1222.13.3403 Boehringer Ingelheim Investigational Site
  • Tabor, Czech Republic
    • 1222.13.3402 Boehringer Ingelheim Investigational Site
• Denmark
  • Aalborg, Denmark
    • 1222.13.2003 Boehringer Ingelheim Investigational Site
  • Hvidovre, Denmark
    • 1222.13.2002 Boehringer Ingelheim Investigational Site
  • Silkeborg, Denmark
    • 1222.13.2001 Boehringer Ingelheim Investigational Site
• Finland
  • Lahti, Finland
    • 1222.13.2103 Boehringer Ingelheim Investigational Site
  • Tampere, Finland
    • 1222.13.2101 Boehringer Ingelheim Investigational Site
  • Turku, Finland
    • 1222.13.2102 Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1222.13.1502 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1222.13.1503 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1222.13.1506 Boehringer Ingelheim Investigational Site
  • Dortmund, Germany
    • 1222.13.1511 Boehringer Ingelheim Investigational Site
  • Essen, Germany
    • 1222.13.1514 Boehringer Ingelheim Investigational Site
  • Großhansdorf, Germany
    • 1222.13.1509 Boehringer Ingelheim Investigational Site
  • Hannover, Germany
    • 1222.13.1508 Boehringer Ingelheim Investigational Site
  • Hannover, Germany
    • 1222.13.1510 Boehringer Ingelheim Investigational Site
  • Kiel, Germany
    • 1222.13.1512 Boehringer Ingelheim Investigational Site
  • Köln, Germany
    • 1222.13.1501 Boehringer Ingelheim Investigational Site
  • Reinfeld, Germany
    • 1222.13.1505 Boehringer Ingelheim Investigational Site
  • Schwerin, Germany
    • 1222.13.1507 Boehringer Ingelheim Investigational Site
• Hong Kong
  • Kowloon, Hong Kong
    • 1222.13.2901 Boehringer Ingelheim Investigational Site
• India
  • Bangalore, India
    • 1222.13.2804 Boehringer Ingelheim Investigational Site
  • Chennai, India
    • 1222.13.2803 Boehringer Ingelheim Investigational Site
  • Coimbatore-, India
    • 1222.13.2806 Boehringer Ingelheim Investigational Site
  • Hyderabad, India
    • 1222.13.2810 Boehringer Ingelheim Investigational Site
  • Indore, India
    • 1222.13.2801 Boehringer Ingelheim Investigational Site
  • Indore, India
    • 1222.13.2807 Boehringer Ingelheim Investigational Site
  • Jaipur, India
    • 1222.13.2805 Boehringer Ingelheim Investigational Site
  • Ludhiana, Punjab, India
    • 1222.13.2802 Boehringer Ingelheim Investigational Site
  • Mumbai, India
    • 1222.13.2809 Boehringer Ingelheim Investigational Site
  • Mumbai, India
    • 1222.13.2812 Boehringer Ingelheim Investigational Site
  • Pune, India
    • 1222.13.2811 Boehringer Ingelheim Investigational Site
• Italy
  • Catania, Italy
    • 1222.13.1704 Boehringer Ingelheim Investigational Site
  • Genova, Italy
    • 1222.13.1702 Boehringer Ingelheim Investigational Site
  • Pisa, Italy
    • 1222.13.1701 Boehringer Ingelheim Investigational Site
  • Siena, Italy
    • 1222.13.1705 Boehringer Ingelheim Investigational Site
  • Trieste, Italy
    • 1222.13.1703 Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Gwangju, Korea, Republic of
    • 1222.13.2701 Boehringer Ingelheim Investigational Site
  • Incheon, Korea, Republic of
    • 1222.13.2702 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1222.13.2703 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1222.13.2705 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1222.13.2706 Boehringer Ingelheim Investigational Site
  • Suwon, Korea, Republic of
    • 1222.13.2704 Boehringer Ingelheim Investigational Site
• Malaysia
  • Batu Caves, Malaysia
    • 1222.13.3103 Boehringer Ingelheim Investigational Site
  • Kota Kinabalu, Malaysia
    • 1222.13.3101 Boehringer Ingelheim Investigational Site
  • Kuala Lumpur, Malaysia
    • 1222.13.3102 Boehringer Ingelheim Investigational Site
  • Kuantan, Malaysia
    • 1222.13.3104 Boehringer Ingelheim Investigational Site
• Norway
  • Bergen, Norway
    • 1222.13.2201 Boehringer Ingelheim Investigational Site
  • Oslo, Norway
    • 1222.13.2202 Boehringer Ingelheim Investigational Site
• Philippines
  • Cebu, Philippines
    • 1222.13.3203 Boehringer Ingelheim Investigational Site
  • Quezon City, Philippines
    • 1222.13.3201 Boehringer Ingelheim Investigational Site
  • Quezon City, Philippines
    • 1222.13.3202 Boehringer Ingelheim Investigational Site
• South Africa
  • Durban, South Africa
    • 1222.13.2302 Boehringer Ingelheim Investigational Site
  • Pretoria, South Africa
    • 1222.13.2301 Boehringer Ingelheim Investigational Site
• Spain
  • Aranjuez, Spain
    • 1222.13.1803 Boehringer Ingelheim Investigational Site
  • Elda, Spain
    • 1222.13.1806 Boehringer Ingelheim Investigational Site
  • Els Hostalets de Balenyà, Spain
    • 1222.13.1802 Boehringer Ingelheim Investigational Site
  • Pozuelo de Alarcón, Spain
    • 1222.13.1804 Boehringer Ingelheim Investigational Site
  • Valladolid, Spain
    • 1222.13.1805 Boehringer Ingelheim Investigational Site
  • Vic (Barcelona), Spain
    • 1222.13.1801 Boehringer Ingelheim Investigational Site
• Sweden
  • Boden, Sweden
    • 1222.13.1901 Boehringer Ingelheim Investigational Site
  • Sundsvall, Sweden
    • 1222.13.1902 Boehringer Ingelheim Investigational Site
• Thailand
  • Bangkok, Thailand
    • 1222.13.3302 Boehringer Ingelheim Investigational Site
  • Bangkok, Thailand
    • 1222.13.3303 Boehringer Ingelheim Investigational Site
  • Chiang Mai, Thailand
    • 1222.13.3301 Boehringer Ingelheim Investigational Site
• Ukraine
  • Ivano-Frankivsk, Ukraine
    • 1222.13.3602 Boehringer Ingelheim Investigational Site
  • Kharkiv, Ukraine
    • 1222.13.3601 Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine
    • 1222.13.3603 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:

1. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:post-bronchodilator FEV1<80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC <70% at Visit 1
2. Male or female patients, 40 years of age or older
3. Patients must be current or ex-smokers with a smoking history of more than 10 pack years:

Exclusion criteria:

1. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT >x2 ULN, SGPT >x2 ULN, bilirubin >x2 ULN or creatinine >x2 ULN
2. Patients with a history of asthma and/or total blood eosinophil count greater than 600/mm3
3. Patients with thyrotoxicosis, paroxysmal tachycardia (>100 beats per minute)
4. Patients with a history of myocardial infarction within 1 year of screening visit, unstable or life-threatening cardiac arrhythmia, hospitalization 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, life-threatening pulmonary obstruction, cystic fibrosis, clinically evident bronchiectasis, significant alcohol or drug abuse
5. Patients who have undergone thoracotomy with pulmonary resection
6. Patients being treated with oral beta-adrenergics or oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
7. Patients who regularly use daytime oxygen therapy for more than one hour per day.
8. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program
9. Pregnant or nursing women
10. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

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 (BI 1744); 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 (BI 1744); Comparison of low and high doses on efficacy and safety in COPD patients
Active Comparator: Formoterol 12mcg; 12mcg inhaled twice daily from the Aerolizer inhaler	Drug: Formoterol; Active comparator with Olodaterol (BI 1744) on safety and efficacy in COPD patients
Placebo Comparator: Placebo; Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler	Drug: Placebo; Placebo for comparison with Olodaterol (BI 1744) on safety and efficacy in COPD patients; Drug: Placebo; Placebo for comparison Formoterolon safety and efficacy in COPD patients

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 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 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 Week 24
Trough FEV1 Response 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.	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.
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks	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).	Baseline, Week 24
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis	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).	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks	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).	Baseline, Week 24
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks	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).	Baseline, Week 12
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks	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).	Baseline, Week 48
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis	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.	Baseline, Week 24
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 2
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 6
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 Week 12
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 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 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 Week 48
Trough FEV1 Response 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.	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.
Trough FEV1 Response 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.	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 FEV1 Response 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.	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	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 at week 18.
Trough FEV1 Response 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.	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	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 at week 40.
Trough FEV1 Response 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.	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.
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks	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.	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	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.	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 Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks	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.	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	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.	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	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.	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	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.	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.
Trough FVC Response 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.	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 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.	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	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.	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.
Trough FVC Response 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.	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	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.	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 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.	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.
Trough FVC Response 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.	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 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.	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 FVC (0-3h) Response 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.	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 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.	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 FVC (0-3h) Response 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.	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 FVC (0-3h) Response 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.	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	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.	Week 24
Use of Rescue Medication at Week 24	Mean number of puffs of rescue medication used per day (daytime/nighttime/total)	Week 24
Patient's Global Rating (PGR) at 6 Weeks	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).	Week 6
Patient's Global Rating (PGR) at 12 Weeks	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).	Week 12
Patient's Global Rating (PGR) at 24 Weeks	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).	Week 24
Patient's Global Rating (PGR) at 48 Weeks	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).	Week 48
Mahler Transitional Dyspnea Index Focal Score at 6 Weeks	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).	Baseline, Week 6
Mahler Transitional Dyspnea Index Focal Score at 12 Weeks	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).	Baseline, Week 12
Mahler Transitional Dyspnea Index Focal Score at 18 Weeks	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).	Baseline, Week 18
Mahler Transitional Dyspnea Index Focal Score at 32 Weeks	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).	Baseline, Week 32
Mahler Transitional Dyspnea Index Focal Score at 40 Weeks	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).	Baseline, Week 40
Mahler Transitional Dyspnea Index Focal Score at 48 Weeks	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).	Baseline, 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.	Baseline to end of study at 48 weeks.
Time to First Chronic Obstructive Pulmonary Disease (CPOD) 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.	Baseline to end of study at 48 weeks.
Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) 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.	Baseline to end of study at 48 weeks.
Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) 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.
Absolute Plasma Concentrations	Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.	within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18
Changes in Safety Parameters Related to Treatment	Occurence of cardiac disorders and investigations related to treatment.	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.
• Koch A, Pizzichini E, Hamilton A, Hart L, Korducki L, De Salvo MC, Paggiaro P. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat(R) versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014 Jul 5;9:697-714. doi: 10.2147/COPD.S62502. eCollection 2014.

Helpful Links

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Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: November 18, 2008
• First Submitted That Met QC Criteria: November 18, 2008
• First Posted (Estimate): November 19, 2008

Study Record Updates

• Last Update Posted (Estimate): June 27, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Olodaterol; Formoterol Fumarate
• Other Study ID Numbers: 1222.13; 2008-001933-84 (EudraCT Number: EudraCT)