search
Back to results

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

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Olodaterol (BI 1744)
Olodaterol (BI 1744)
Formoterol
Placebo
Placebo
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • 1222.13.2401 Boehringer Ingelheim Investigational Site
  • 1222.13.2403 Boehringer Ingelheim Investigational Site
  • 1222.13.2402 Boehringer Ingelheim Investigational Site
  • 1222.13.2404 Boehringer Ingelheim Investigational Site
  • 1222.13.2502 Boehringer Ingelheim Investigational Site
  • 1222.13.2503 Boehringer Ingelheim Investigational Site
  • 1222.13.2505 Boehringer Ingelheim Investigational Site
  • 1222.13.2501 Boehringer Ingelheim Investigational Site
  • 1222.13.2504 Boehringer Ingelheim Investigational Site
  • 1222.13.1408 Boehringer Ingelheim Investigational Site
  • 1222.13.1407 Boehringer Ingelheim Investigational Site
  • 1222.13.1403 Boehringer Ingelheim Investigational Site
  • 1222.13.1412 Boehringer Ingelheim Investigational Site
  • 1222.13.1401 Boehringer Ingelheim Investigational Site
  • 1222.13.1410 Boehringer Ingelheim Investigational Site
  • 1222.13.1413 Boehringer Ingelheim Investigational Site
  • 1222.13.1404 Boehringer Ingelheim Investigational Site
  • 1222.13.1411 Boehringer Ingelheim Investigational Site
  • 1222.13.1406 Boehringer Ingelheim Investigational Site
  • 1222.13.1402 Boehringer Ingelheim Investigational Site
  • 1222.13.3502 Boehringer Ingelheim Investigational Site
  • 1222.13.3503 Boehringer Ingelheim Investigational Site
  • 1222.13.3504 Boehringer Ingelheim Investigational Site
  • 1222.13.3501 Boehringer Ingelheim Investigational Site
  • 1222.13.3401 Boehringer Ingelheim Investigational Site
  • 1222.13.3403 Boehringer Ingelheim Investigational Site
  • 1222.13.3402 Boehringer Ingelheim Investigational Site
  • 1222.13.2003 Boehringer Ingelheim Investigational Site
  • 1222.13.2002 Boehringer Ingelheim Investigational Site
  • 1222.13.2001 Boehringer Ingelheim Investigational Site
  • 1222.13.2103 Boehringer Ingelheim Investigational Site
  • 1222.13.2101 Boehringer Ingelheim Investigational Site
  • 1222.13.2102 Boehringer Ingelheim Investigational Site
  • 1222.13.1502 Boehringer Ingelheim Investigational Site
  • 1222.13.1503 Boehringer Ingelheim Investigational Site
  • 1222.13.1506 Boehringer Ingelheim Investigational Site
  • 1222.13.1511 Boehringer Ingelheim Investigational Site
  • 1222.13.1514 Boehringer Ingelheim Investigational Site
  • 1222.13.1509 Boehringer Ingelheim Investigational Site
  • 1222.13.1508 Boehringer Ingelheim Investigational Site
  • 1222.13.1510 Boehringer Ingelheim Investigational Site
  • 1222.13.1512 Boehringer Ingelheim Investigational Site
  • 1222.13.1501 Boehringer Ingelheim Investigational Site
  • 1222.13.1505 Boehringer Ingelheim Investigational Site
  • 1222.13.1507 Boehringer Ingelheim Investigational Site
  • 1222.13.2901 Boehringer Ingelheim Investigational Site
  • 1222.13.2804 Boehringer Ingelheim Investigational Site
  • 1222.13.2803 Boehringer Ingelheim Investigational Site
  • 1222.13.2806 Boehringer Ingelheim Investigational Site
  • 1222.13.2810 Boehringer Ingelheim Investigational Site
  • 1222.13.2801 Boehringer Ingelheim Investigational Site
  • 1222.13.2807 Boehringer Ingelheim Investigational Site
  • 1222.13.2805 Boehringer Ingelheim Investigational Site
  • 1222.13.2802 Boehringer Ingelheim Investigational Site
  • 1222.13.2809 Boehringer Ingelheim Investigational Site
  • 1222.13.2812 Boehringer Ingelheim Investigational Site
  • 1222.13.2811 Boehringer Ingelheim Investigational Site
  • 1222.13.1704 Boehringer Ingelheim Investigational Site
  • 1222.13.1702 Boehringer Ingelheim Investigational Site
  • 1222.13.1701 Boehringer Ingelheim Investigational Site
  • 1222.13.1705 Boehringer Ingelheim Investigational Site
  • 1222.13.1703 Boehringer Ingelheim Investigational Site
  • 1222.13.2701 Boehringer Ingelheim Investigational Site
  • 1222.13.2702 Boehringer Ingelheim Investigational Site
  • 1222.13.2703 Boehringer Ingelheim Investigational Site
  • 1222.13.2705 Boehringer Ingelheim Investigational Site
  • 1222.13.2706 Boehringer Ingelheim Investigational Site
  • 1222.13.2704 Boehringer Ingelheim Investigational Site
  • 1222.13.3103 Boehringer Ingelheim Investigational Site
  • 1222.13.3101 Boehringer Ingelheim Investigational Site
  • 1222.13.3102 Boehringer Ingelheim Investigational Site
  • 1222.13.3104 Boehringer Ingelheim Investigational Site
  • 1222.13.2201 Boehringer Ingelheim Investigational Site
  • 1222.13.2202 Boehringer Ingelheim Investigational Site
  • 1222.13.3203 Boehringer Ingelheim Investigational Site
  • 1222.13.3201 Boehringer Ingelheim Investigational Site
  • 1222.13.3202 Boehringer Ingelheim Investigational Site
  • 1222.13.2302 Boehringer Ingelheim Investigational Site
  • 1222.13.2301 Boehringer Ingelheim Investigational Site
  • 1222.13.1803 Boehringer Ingelheim Investigational Site
  • 1222.13.1806 Boehringer Ingelheim Investigational Site
  • 1222.13.1802 Boehringer Ingelheim Investigational Site
  • 1222.13.1804 Boehringer Ingelheim Investigational Site
  • 1222.13.1805 Boehringer Ingelheim Investigational Site
  • 1222.13.1801 Boehringer Ingelheim Investigational Site
  • 1222.13.1901 Boehringer Ingelheim Investigational Site
  • 1222.13.1902 Boehringer Ingelheim Investigational Site
  • 1222.13.3302 Boehringer Ingelheim Investigational Site
  • 1222.13.3303 Boehringer Ingelheim Investigational Site
  • 1222.13.3301 Boehringer Ingelheim Investigational Site
  • 1222.13.3602 Boehringer Ingelheim Investigational Site
  • 1222.13.3601 Boehringer Ingelheim Investigational Site
  • 1222.13.3603 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Placebo Comparator

Arm Label

Olodaterol (BI 1744) Low

Olodaterol (BI 1744) High

Formoterol 12mcg

Placebo

Arm Description

Low dose inhaled orally once daily from the Respimat inhaler

High dose inhaled orally once daily from the Respimat inhaler

12mcg inhaled twice daily from the Aerolizer inhaler

Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler

Outcomes

Primary Outcome Measures

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.
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.
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).
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).

Secondary Outcome Measures

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).
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Use of Rescue Medication at Week 24
Mean number of puffs of rescue medication used per day (daytime/nighttime/total)
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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.
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.
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.
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.
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.
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.
Absolute Plasma Concentrations
Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.
Changes in Safety Parameters Related to Treatment
Occurence of cardiac disorders and investigations related to treatment.

Full Information

First Posted
November 18, 2008
Last Updated
June 17, 2014
Sponsor
Boehringer Ingelheim
search

1. Study Identification

Unique Protocol Identification Number
NCT00793624
Brief Title
Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease I
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
906 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Olodaterol (BI 1744) Low
Arm Type
Experimental
Arm Description
Low dose inhaled orally once daily from the Respimat inhaler
Arm Title
Olodaterol (BI 1744) High
Arm Type
Experimental
Arm Description
High dose inhaled orally once daily from the Respimat inhaler
Arm Title
Formoterol 12mcg
Arm Type
Active Comparator
Arm Description
12mcg inhaled twice daily from the Aerolizer inhaler
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler
Intervention Type
Drug
Intervention Name(s)
Olodaterol (BI 1744)
Intervention Description
Comparison of low and high doses on efficacy and safety in COPD patients
Intervention Type
Drug
Intervention Name(s)
Olodaterol (BI 1744)
Intervention Description
Comparison of low and high doses on efficacy and safety in COPD patients
Intervention Type
Drug
Intervention Name(s)
Formoterol
Intervention Description
Active comparator with Olodaterol (BI 1744) on safety and efficacy in COPD patients
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for comparison with Olodaterol (BI 1744) on safety and efficacy in COPD patients
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for comparison Formoterolon safety and efficacy in COPD patients
Primary Outcome Measure Information:
Title
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
Title
Trough FEV1 Response at Week 24
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
Title
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
Description
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).
Time Frame
Baseline, Week 24
Title
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
Description
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).
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks
Description
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).
Time Frame
Baseline, Week 24
Title
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks
Description
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).
Time Frame
Baseline, Week 12
Title
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks
Description
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).
Time Frame
Baseline, Week 48
Title
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis
Description
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.
Time Frame
Baseline, Week 24
Title
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
Title
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
Title
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
Title
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
Title
Trough FEV1 Response at Week 2
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
Title
Trough FEV1 Response at Week 6
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
Title
Trough FEV1 Response at Week 12
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
Title
Trough FEV1 Response at Week 18
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
Title
Trough FEV1 Response at Week 32
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
Title
Trough FEV1 Response at Week 40
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
Title
Trough FEV1 Response at Week 48
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
Title
Peak FEV1 (0-3h) Response After 2 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Title
Peak FEV1 (0-3h) Response After 6 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Title
Peak FEV1 (0-3h) Response After 12 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
Title
Peak FEV1 (0-3h) Response After 24 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Title
Peak FEV1 (0-3h) Response After 48 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Title
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
Title
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
Title
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
Title
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
Title
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
Title
Trough FVC Response at Week 2
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
Title
Trough FVC Response at Week 6
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
Title
Trough FVC Response at Week 12
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
Title
Trough FVC Response at Week 18
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
Title
Trough FVC Response at Week 24
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
Title
Trough FVC Response at Week 32
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
Title
Trough FVC Response at Week 48
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
Title
Trough FVC Response at Week 40
Description
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.
Time Frame
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
Title
Peak FVC (0-3h) Response After 2 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Title
Peak FVC (0-3h) Response After 6 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
Title
Peak FVC (0-3h) Response After 12 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
Title
Peak FVC (0-3h) Response After 24 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
Title
Peak FVC (0-3h) Response After 48 Weeks
Description
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.
Time Frame
1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
Title
Peak Expiratory Flow Rate (PEFR) at Week 24
Description
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.
Time Frame
Week 24
Title
Use of Rescue Medication at Week 24
Description
Mean number of puffs of rescue medication used per day (daytime/nighttime/total)
Time Frame
Week 24
Title
Patient's Global Rating (PGR) at 6 Weeks
Description
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame
Week 6
Title
Patient's Global Rating (PGR) at 12 Weeks
Description
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame
Week 12
Title
Patient's Global Rating (PGR) at 24 Weeks
Description
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame
Week 24
Title
Patient's Global Rating (PGR) at 48 Weeks
Description
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame
Week 48
Title
Mahler Transitional Dyspnea Index Focal Score at 6 Weeks
Description
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).
Time Frame
Baseline, Week 6
Title
Mahler Transitional Dyspnea Index Focal Score at 12 Weeks
Description
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).
Time Frame
Baseline, Week 12
Title
Mahler Transitional Dyspnea Index Focal Score at 18 Weeks
Description
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).
Time Frame
Baseline, Week 18
Title
Mahler Transitional Dyspnea Index Focal Score at 32 Weeks
Description
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).
Time Frame
Baseline, Week 32
Title
Mahler Transitional Dyspnea Index Focal Score at 40 Weeks
Description
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).
Time Frame
Baseline, Week 40
Title
Mahler Transitional Dyspnea Index Focal Score at 48 Weeks
Description
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).
Time Frame
Baseline, Week 48
Title
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Description
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.
Time Frame
Baseline to end of study at 48 weeks.
Title
Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization
Description
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.
Time Frame
Baseline to end of study at 48 weeks.
Title
Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation
Description
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.
Time Frame
Baseline to end of study at 48 weeks.
Title
Number of COPD Exacerbations
Description
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 Frame
Baseline to end of study at week 48 visit
Title
Number of COPD Exacerbations Requiring Hospitalization
Description
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 Frame
Baseline to end of study at week 48 visit
Title
Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations
Description
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 Frame
Baseline to end of study at 48 weeks.
Title
Absolute Plasma Concentrations
Description
Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.
Time Frame
within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18
Title
Changes in Safety Parameters Related to Treatment
Description
Occurence of cardiac disorders and investigations related to treatment.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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 Male or female patients, 40 years of age or older Patients must be current or ex-smokers with a smoking history of more than 10 pack years: Exclusion criteria: 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 Patients with a history of asthma and/or total blood eosinophil count greater than 600/mm3 Patients with thyrotoxicosis, paroxysmal tachycardia (>100 beats per minute) 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 Patients who have undergone thoracotomy with pulmonary resection 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. Patients who regularly use daytime oxygen therapy for more than one hour per day. 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 Pregnant or nursing women Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1222.13.2401 Boehringer Ingelheim Investigational Site
City
Capital Federal
Country
Argentina
Facility Name
1222.13.2403 Boehringer Ingelheim Investigational Site
City
Capital Federal
Country
Argentina
Facility Name
1222.13.2402 Boehringer Ingelheim Investigational Site
City
Mar del Plata
Country
Argentina
Facility Name
1222.13.2404 Boehringer Ingelheim Investigational Site
City
Monte Grande
Country
Argentina
Facility Name
1222.13.2502 Boehringer Ingelheim Investigational Site
City
Juiz de Fora
Country
Brazil
Facility Name
1222.13.2503 Boehringer Ingelheim Investigational Site
City
Rio de Janeiro
Country
Brazil
Facility Name
1222.13.2505 Boehringer Ingelheim Investigational Site
City
Rio de Janeiro
Country
Brazil
Facility Name
1222.13.2501 Boehringer Ingelheim Investigational Site
City
Sao Paulo
Country
Brazil
Facility Name
1222.13.2504 Boehringer Ingelheim Investigational Site
City
Sao Paulo
Country
Brazil
Facility Name
1222.13.1408 Boehringer Ingelheim Investigational Site
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
1222.13.1407 Boehringer Ingelheim Investigational Site
City
Chilliwack
State/Province
British Columbia
Country
Canada
Facility Name
1222.13.1403 Boehringer Ingelheim Investigational Site
City
Downsview
State/Province
Ontario
Country
Canada
Facility Name
1222.13.1412 Boehringer Ingelheim Investigational Site
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
1222.13.1401 Boehringer Ingelheim Investigational Site
City
Niagara Falls
State/Province
Ontario
Country
Canada
Facility Name
1222.13.1410 Boehringer Ingelheim Investigational Site
City
Sarnia
State/Province
Ontario
Country
Canada
Facility Name
1222.13.1413 Boehringer Ingelheim Investigational Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
1222.13.1404 Boehringer Ingelheim Investigational Site
City
La Malbaie
State/Province
Quebec
Country
Canada
Facility Name
1222.13.1411 Boehringer Ingelheim Investigational Site
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
1222.13.1406 Boehringer Ingelheim Investigational Site
City
Point Claire
State/Province
Quebec
Country
Canada
Facility Name
1222.13.1402 Boehringer Ingelheim Investigational Site
City
Saskatoon
State/Province
Saskatchewan
Country
Canada
Facility Name
1222.13.3502 Boehringer Ingelheim Investigational Site
City
Dubrovnik
Country
Croatia
Facility Name
1222.13.3503 Boehringer Ingelheim Investigational Site
City
Rijeka
Country
Croatia
Facility Name
1222.13.3504 Boehringer Ingelheim Investigational Site
City
Split
Country
Croatia
Facility Name
1222.13.3501 Boehringer Ingelheim Investigational Site
City
Zagreb
Country
Croatia
Facility Name
1222.13.3401 Boehringer Ingelheim Investigational Site
City
Beroun
Country
Czech Republic
Facility Name
1222.13.3403 Boehringer Ingelheim Investigational Site
City
Cesky Tesin
Country
Czech Republic
Facility Name
1222.13.3402 Boehringer Ingelheim Investigational Site
City
Tabor
Country
Czech Republic
Facility Name
1222.13.2003 Boehringer Ingelheim Investigational Site
City
Aalborg
Country
Denmark
Facility Name
1222.13.2002 Boehringer Ingelheim Investigational Site
City
Hvidovre
Country
Denmark
Facility Name
1222.13.2001 Boehringer Ingelheim Investigational Site
City
Silkeborg
Country
Denmark
Facility Name
1222.13.2103 Boehringer Ingelheim Investigational Site
City
Lahti
Country
Finland
Facility Name
1222.13.2101 Boehringer Ingelheim Investigational Site
City
Tampere
Country
Finland
Facility Name
1222.13.2102 Boehringer Ingelheim Investigational Site
City
Turku
Country
Finland
Facility Name
1222.13.1502 Boehringer Ingelheim Investigational Site
City
Berlin
Country
Germany
Facility Name
1222.13.1503 Boehringer Ingelheim Investigational Site
City
Berlin
Country
Germany
Facility Name
1222.13.1506 Boehringer Ingelheim Investigational Site
City
Berlin
Country
Germany
Facility Name
1222.13.1511 Boehringer Ingelheim Investigational Site
City
Dortmund
Country
Germany
Facility Name
1222.13.1514 Boehringer Ingelheim Investigational Site
City
Essen
Country
Germany
Facility Name
1222.13.1509 Boehringer Ingelheim Investigational Site
City
Großhansdorf
Country
Germany
Facility Name
1222.13.1508 Boehringer Ingelheim Investigational Site
City
Hannover
Country
Germany
Facility Name
1222.13.1510 Boehringer Ingelheim Investigational Site
City
Hannover
Country
Germany
Facility Name
1222.13.1512 Boehringer Ingelheim Investigational Site
City
Kiel
Country
Germany
Facility Name
1222.13.1501 Boehringer Ingelheim Investigational Site
City
Köln
Country
Germany
Facility Name
1222.13.1505 Boehringer Ingelheim Investigational Site
City
Reinfeld
Country
Germany
Facility Name
1222.13.1507 Boehringer Ingelheim Investigational Site
City
Schwerin
Country
Germany
Facility Name
1222.13.2901 Boehringer Ingelheim Investigational Site
City
Kowloon
Country
Hong Kong
Facility Name
1222.13.2804 Boehringer Ingelheim Investigational Site
City
Bangalore
Country
India
Facility Name
1222.13.2803 Boehringer Ingelheim Investigational Site
City
Chennai
Country
India
Facility Name
1222.13.2806 Boehringer Ingelheim Investigational Site
City
Coimbatore-
Country
India
Facility Name
1222.13.2810 Boehringer Ingelheim Investigational Site
City
Hyderabad
Country
India
Facility Name
1222.13.2801 Boehringer Ingelheim Investigational Site
City
Indore
Country
India
Facility Name
1222.13.2807 Boehringer Ingelheim Investigational Site
City
Indore
Country
India
Facility Name
1222.13.2805 Boehringer Ingelheim Investigational Site
City
Jaipur
Country
India
Facility Name
1222.13.2802 Boehringer Ingelheim Investigational Site
City
Ludhiana, Punjab
Country
India
Facility Name
1222.13.2809 Boehringer Ingelheim Investigational Site
City
Mumbai
Country
India
Facility Name
1222.13.2812 Boehringer Ingelheim Investigational Site
City
Mumbai
Country
India
Facility Name
1222.13.2811 Boehringer Ingelheim Investigational Site
City
Pune
Country
India
Facility Name
1222.13.1704 Boehringer Ingelheim Investigational Site
City
Catania
Country
Italy
Facility Name
1222.13.1702 Boehringer Ingelheim Investigational Site
City
Genova
Country
Italy
Facility Name
1222.13.1701 Boehringer Ingelheim Investigational Site
City
Pisa
Country
Italy
Facility Name
1222.13.1705 Boehringer Ingelheim Investigational Site
City
Siena
Country
Italy
Facility Name
1222.13.1703 Boehringer Ingelheim Investigational Site
City
Trieste
Country
Italy
Facility Name
1222.13.2701 Boehringer Ingelheim Investigational Site
City
Gwangju
Country
Korea, Republic of
Facility Name
1222.13.2702 Boehringer Ingelheim Investigational Site
City
Incheon
Country
Korea, Republic of
Facility Name
1222.13.2703 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1222.13.2705 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1222.13.2706 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1222.13.2704 Boehringer Ingelheim Investigational Site
City
Suwon
Country
Korea, Republic of
Facility Name
1222.13.3103 Boehringer Ingelheim Investigational Site
City
Batu Caves
Country
Malaysia
Facility Name
1222.13.3101 Boehringer Ingelheim Investigational Site
City
Kota Kinabalu
Country
Malaysia
Facility Name
1222.13.3102 Boehringer Ingelheim Investigational Site
City
Kuala Lumpur
Country
Malaysia
Facility Name
1222.13.3104 Boehringer Ingelheim Investigational Site
City
Kuantan
Country
Malaysia
Facility Name
1222.13.2201 Boehringer Ingelheim Investigational Site
City
Bergen
Country
Norway
Facility Name
1222.13.2202 Boehringer Ingelheim Investigational Site
City
Oslo
Country
Norway
Facility Name
1222.13.3203 Boehringer Ingelheim Investigational Site
City
Cebu
Country
Philippines
Facility Name
1222.13.3201 Boehringer Ingelheim Investigational Site
City
Quezon City
Country
Philippines
Facility Name
1222.13.3202 Boehringer Ingelheim Investigational Site
City
Quezon City
Country
Philippines
Facility Name
1222.13.2302 Boehringer Ingelheim Investigational Site
City
Durban
Country
South Africa
Facility Name
1222.13.2301 Boehringer Ingelheim Investigational Site
City
Pretoria
Country
South Africa
Facility Name
1222.13.1803 Boehringer Ingelheim Investigational Site
City
Aranjuez
Country
Spain
Facility Name
1222.13.1806 Boehringer Ingelheim Investigational Site
City
Elda
Country
Spain
Facility Name
1222.13.1802 Boehringer Ingelheim Investigational Site
City
Els Hostalets de Balenyà
Country
Spain
Facility Name
1222.13.1804 Boehringer Ingelheim Investigational Site
City
Pozuelo de Alarcón
Country
Spain
Facility Name
1222.13.1805 Boehringer Ingelheim Investigational Site
City
Valladolid
Country
Spain
Facility Name
1222.13.1801 Boehringer Ingelheim Investigational Site
City
Vic (Barcelona)
Country
Spain
Facility Name
1222.13.1901 Boehringer Ingelheim Investigational Site
City
Boden
Country
Sweden
Facility Name
1222.13.1902 Boehringer Ingelheim Investigational Site
City
Sundsvall
Country
Sweden
Facility Name
1222.13.3302 Boehringer Ingelheim Investigational Site
City
Bangkok
Country
Thailand
Facility Name
1222.13.3303 Boehringer Ingelheim Investigational Site
City
Bangkok
Country
Thailand
Facility Name
1222.13.3301 Boehringer Ingelheim Investigational Site
City
Chiang Mai
Country
Thailand
Facility Name
1222.13.3602 Boehringer Ingelheim Investigational Site
City
Ivano-Frankivsk
Country
Ukraine
Facility Name
1222.13.3601 Boehringer Ingelheim Investigational Site
City
Kharkiv
Country
Ukraine
Facility Name
1222.13.3603 Boehringer Ingelheim Investigational Site
City
Kiev
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
32943047
Citation
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.
Results Reference
derived
PubMed Identifier
32848381
Citation
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.
Results Reference
derived
PubMed Identifier
30077810
Citation
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.
Results Reference
derived
PubMed Identifier
25045258
Citation
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.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1222/1222.13_U10-3194-01-DS.pdf
Description
Related Info
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1222/1222.13_Literature.pdf
Description
Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs