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

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

• Study Type: Interventional
• Enrollment (Actual): 937
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal, Argentina
    • 1222.14.5004 Boehringer Ingelheim Investigational Site
  • Florencio Varela, Argentina
    • 1222.14.5005 Boehringer Ingelheim Investigational Site
  • Mar del Plata, Argentina
    • 1222.14.5003 Boehringer Ingelheim Investigational Site
  • Mendoza, Argentina
    • 1222.14.5001 Boehringer Ingelheim Investigational Site
  • Quilmes, Argentina
    • 1222.14.5002 Boehringer Ingelheim Investigational Site
• Brazil
  • Florianopolis, Brazil
    • 1222.14.5106 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1222.14.5101 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1222.14.5103 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1222.14.5104 Boehringer Ingelheim Investigational Site
  • Recife, Brazil
    • 1222.14.5102 Boehringer Ingelheim Investigational Site
  • Sao Paulo, Brazil
    • 1222.14.5105 Boehringer Ingelheim Investigational Site
• Canada
  • Quebec, Canada
    • 1222.14.4006 Boehringer Ingelheim Investigational Site
  • Alberta
    • Calgary, Alberta, Canada
      • 1222.14.4005 Boehringer Ingelheim Investigational Site
  • British Columbia
    • Kelowna, British Columbia, Canada
      • 1222.14.4002 Boehringer Ingelheim Investigational Site
    • Vancouver, British Columbia, Canada
      • 1222.14.4004 Boehringer Ingelheim Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada
      • 1222.14.4009 Boehringer Ingelheim Investigational Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada
      • 1222.14.4010 Boehringer Ingelheim Investigational Site
  • Ontario
    • Grimsby, Ontario, Canada
      • 1222.14.4008 Boehringer Ingelheim Investigational Site
    • Mississauga, Ontario, Canada
      • 1222.14.4014 Boehringer Ingelheim Investigational Site
    • Newmarket, Ontario, Canada
      • 1222.14.4007 Boehringer Ingelheim Investigational Site
    • Ottawa, Ontario, Canada
      • 1222.14.4013 Boehringer Ingelheim Investigational Site
    • Scarborough, Ontario, Canada
      • 1222.14.4001 Boehringer Ingelheim Investigational Site
  • Quebec
    • Montreal, Quebec, Canada
      • 1222.14.4012 Boehringer Ingelheim Investigational Site
    • Sherbrooke, Quebec, Canada
      • 1222.14.4015 Boehringer Ingelheim Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 1222.14.4011 Boehringer Ingelheim Investigational Site
• Czech Republic
  • Brno, Czech Republic
    • 1222.14.6004 Boehringer Ingelheim Investigational Site
  • Hradec Kralove, Czech Republic
    • 1222.14.6003 Boehringer Ingelheim Investigational Site
  • Kyjov, Czech Republic
    • 1222.14.6002 Boehringer Ingelheim Investigational Site
  • Znojmo, Czech Republic
    • 1222.14.6001 Boehringer Ingelheim Investigational Site
• Denmark
  • Helsingør, Denmark
    • 1222.14.4602 Boehringer Ingelheim Investigational Site
  • Hillerød, Denmark
    • 1222.14.4601 Boehringer Ingelheim Investigational Site
  • Roskilde, Denmark
    • 1222.14.4603 Boehringer Ingelheim Investigational Site
• Finland
  • Espoo, Finland
    • 1222.14.4702 Boehringer Ingelheim Investigational Site
  • HUS, Finland
    • 1222.14.4701 Boehringer Ingelheim Investigational Site
  • Lohja, Finland
    • 1222.14.4703 Boehringer Ingelheim Investigational Site
• Germany
  • Aschaffenburg, Germany
    • 1222.14.4106 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1222.14.4112 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1222.14.4103 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1222.14.4110 Boehringer Ingelheim Investigational Site
  • Gelnhausen, Germany
    • 1222.14.4108 Boehringer Ingelheim Investigational Site
  • Kelkheim, Germany
    • 1222.14.4107 Boehringer Ingelheim Investigational Site
  • Lübeck, Germany
    • 1222.14.4114 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1222.14.4111 Boehringer Ingelheim Investigational Site
  • Minden, Germany
    • 1222.14.4113 Boehringer Ingelheim Investigational Site
  • Mönchengladbach, Germany
    • 1222.14.4109 Boehringer Ingelheim Investigational Site
  • Rodgau-Dudenhofen, Germany
    • 1222.14.4104 Boehringer Ingelheim Investigational Site
  • Wiesloch, Germany
    • 1222.14.4105 Boehringer Ingelheim Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • 1222.14.5501 Boehringer Ingelheim Investigational Site
• India
  • Coimbatore, India
    • 1222.14.5412 Boehringer Ingelheim Investigational Site
  • Hyderabad, India
    • 1222.14.5406 Boehringer Ingelheim Investigational Site
  • Indore, India
    • 1222.14.5402 Boehringer Ingelheim Investigational Site
  • Jaipur, India
    • 1222.14.5405 Boehringer Ingelheim Investigational Site
  • Jaipur, India
    • 1222.14.5409 Boehringer Ingelheim Investigational Site
  • Mangalore, India
    • 1222.14.5403 Boehringer Ingelheim Investigational Site
  • Mysore, India
    • 1222.14.5407 Boehringer Ingelheim Investigational Site
  • Nagpur, India
    • 1222.14.5404 Boehringer Ingelheim Investigational Site
  • Noida, India
    • 1222.14.5408 Boehringer Ingelheim Investigational Site
  • Pune, India
    • 1222.14.5401 Boehringer Ingelheim Investigational Site
  • Vellore, India
    • 1222.14.5410 Boehringer Ingelheim Investigational Site
• Italy
  • Cassano Delle Murge (ba), Italy
    • 1222.14.4301 Boehringer Ingelheim Investigational Site
  • Genova, Italy
    • 1222.14.4302 Boehringer Ingelheim Investigational Site
  • Milano, Italy
    • 1222.14.4304 Boehringer Ingelheim Investigational Site
  • Parma, Italy
    • 1222.14.4305 Boehringer Ingelheim Investigational Site
  • Roma, Italy
    • 1222.14.4303 Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Bucheon, Korea, Republic of
    • 1222.14.5301 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1222.14.5302 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1222.14.5305 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1222.14.5306 Boehringer Ingelheim Investigational Site
  • Uijeongbu, Korea, Republic of
    • 1222.14.5304 Boehringer Ingelheim Investigational Site
  • Wonju, Korea, Republic of
    • 1222.14.5303 Boehringer Ingelheim Investigational Site
• Malaysia
  • Georgetown, Pulau Pinang, Malaysia
    • 1222.14.5701 Boehringer Ingelheim Investigational Site
  • Kuala Lumpur, Malaysia
    • 1222.14.5703 Boehringer Ingelheim Investigational Site
  • Kuching, Sarawak, Malaysia
    • 1222.14.5702 Boehringer Ingelheim Investigational Site
• Norway
  • Fredrikstad, Norway
    • 1222.14.4802 Boehringer Ingelheim Investigational Site
  • SKI, Norway
    • 1222.14.4801 Boehringer Ingelheim Investigational Site
• Philippines
  • Iloilo City, Philippines
    • 1222.14.5802 Boehringer Ingelheim Investigational Site
  • Iloilo City, Philippines
    • 1222.14.5803 Boehringer Ingelheim Investigational Site
  • Manila, Philippines
    • 1222.14.5801 Boehringer Ingelheim Investigational Site
• Romania
  • Brasov, Romania
    • 1222.14.6103 Boehringer Ingelheim Investigational Site
  • Constanta, Romania
    • 1222.14.6102 Boehringer Ingelheim Investigational Site
  • Iasi, Romania
    • 1222.14.6101 Boehringer Ingelheim Investigational Site
• Russian Federation
  • Petrozavodsk, Russian Federation
    • 1222.14.6203 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 1222.14.6201 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 1222.14.6202 Boehringer Ingelheim Investigational Site
• South Africa
  • Cape Town, South Africa
    • 1222.14.4901 Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa
    • 1222.14.4902 Boehringer Ingelheim Investigational Site
• Spain
  • Barcelona, Spain
    • 1222.14.4401 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1222.14.4402 Boehringer Ingelheim Investigational Site
  • Madrid, Spain
    • 1222.14.4406 Boehringer Ingelheim Investigational Site
  • Mérida, Spain
    • 1222.14.4405 Boehringer Ingelheim Investigational Site
  • Palma de Mallorca, Spain
    • 1222.14.4403 Boehringer Ingelheim Investigational Site
  • Terrassa (Barcelona), Spain
    • 1222.14.4407 Boehringer Ingelheim Investigational Site
• Sweden
  • Boden, Sweden
    • 1222.14.4501 Boehringer Ingelheim Investigational Site
  • Göteboerg, Sweden
    • 1222.14.4503 Boehringer Ingelheim Investigational Site
  • Lund, Sweden
    • 1222.14.4502 Boehringer Ingelheim Investigational Site
• Thailand
  • Bangkok, Thailand
    • 1222.14.5904 Boehringer Ingelheim Investigational Site
  • Khon Kaen, Thailand
    • 1222.14.5901 Boehringer Ingelheim Investigational Site
  • Songkla, Thailand
    • 1222.14.5902 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 devices for comparison with Olodaterol (BI 1744) on 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.
Changes in Safety Parameters Related to Treatment	Occurence of cardiac disorders and investigations related to treatment.	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 study drug administration and 10 minutes post-dose at week 6, 12 and 18

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: January 1, 2009
• Primary Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: November 21, 2008
• First Submitted That Met QC Criteria: November 21, 2008
• First Posted (Estimate): November 24, 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: 1222.14; 2008-001934-28 (EudraCT Number: EudraCT)