Back to resultsSafety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease II
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
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
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).
Sites / Locations
- 1222.14.5004 Boehringer Ingelheim Investigational Site
- 1222.14.5005 Boehringer Ingelheim Investigational Site
- 1222.14.5003 Boehringer Ingelheim Investigational Site
- 1222.14.5001 Boehringer Ingelheim Investigational Site
- 1222.14.5002 Boehringer Ingelheim Investigational Site
- 1222.14.5106 Boehringer Ingelheim Investigational Site
- 1222.14.5101 Boehringer Ingelheim Investigational Site
- 1222.14.5103 Boehringer Ingelheim Investigational Site
- 1222.14.5104 Boehringer Ingelheim Investigational Site
- 1222.14.5102 Boehringer Ingelheim Investigational Site
- 1222.14.5105 Boehringer Ingelheim Investigational Site
- 1222.14.4005 Boehringer Ingelheim Investigational Site
- 1222.14.4002 Boehringer Ingelheim Investigational Site
- 1222.14.4004 Boehringer Ingelheim Investigational Site
- 1222.14.4009 Boehringer Ingelheim Investigational Site
- 1222.14.4010 Boehringer Ingelheim Investigational Site
- 1222.14.4008 Boehringer Ingelheim Investigational Site
- 1222.14.4014 Boehringer Ingelheim Investigational Site
- 1222.14.4007 Boehringer Ingelheim Investigational Site
- 1222.14.4013 Boehringer Ingelheim Investigational Site
- 1222.14.4001 Boehringer Ingelheim Investigational Site
- 1222.14.4012 Boehringer Ingelheim Investigational Site
- 1222.14.4015 Boehringer Ingelheim Investigational Site
- 1222.14.4011 Boehringer Ingelheim Investigational Site
- 1222.14.4006 Boehringer Ingelheim Investigational Site
- 1222.14.6004 Boehringer Ingelheim Investigational Site
- 1222.14.6003 Boehringer Ingelheim Investigational Site
- 1222.14.6002 Boehringer Ingelheim Investigational Site
- 1222.14.6001 Boehringer Ingelheim Investigational Site
- 1222.14.4602 Boehringer Ingelheim Investigational Site
- 1222.14.4601 Boehringer Ingelheim Investigational Site
- 1222.14.4603 Boehringer Ingelheim Investigational Site
- 1222.14.4702 Boehringer Ingelheim Investigational Site
- 1222.14.4701 Boehringer Ingelheim Investigational Site
- 1222.14.4703 Boehringer Ingelheim Investigational Site
- 1222.14.4106 Boehringer Ingelheim Investigational Site
- 1222.14.4112 Boehringer Ingelheim Investigational Site
- 1222.14.4103 Boehringer Ingelheim Investigational Site
- 1222.14.4110 Boehringer Ingelheim Investigational Site
- 1222.14.4108 Boehringer Ingelheim Investigational Site
- 1222.14.4107 Boehringer Ingelheim Investigational Site
- 1222.14.4114 Boehringer Ingelheim Investigational Site
- 1222.14.4111 Boehringer Ingelheim Investigational Site
- 1222.14.4113 Boehringer Ingelheim Investigational Site
- 1222.14.4109 Boehringer Ingelheim Investigational Site
- 1222.14.4104 Boehringer Ingelheim Investigational Site
- 1222.14.4105 Boehringer Ingelheim Investigational Site
- 1222.14.5501 Boehringer Ingelheim Investigational Site
- 1222.14.5412 Boehringer Ingelheim Investigational Site
- 1222.14.5406 Boehringer Ingelheim Investigational Site
- 1222.14.5402 Boehringer Ingelheim Investigational Site
- 1222.14.5405 Boehringer Ingelheim Investigational Site
- 1222.14.5409 Boehringer Ingelheim Investigational Site
- 1222.14.5403 Boehringer Ingelheim Investigational Site
- 1222.14.5407 Boehringer Ingelheim Investigational Site
- 1222.14.5404 Boehringer Ingelheim Investigational Site
- 1222.14.5408 Boehringer Ingelheim Investigational Site
- 1222.14.5401 Boehringer Ingelheim Investigational Site
- 1222.14.5410 Boehringer Ingelheim Investigational Site
- 1222.14.4301 Boehringer Ingelheim Investigational Site
- 1222.14.4302 Boehringer Ingelheim Investigational Site
- 1222.14.4304 Boehringer Ingelheim Investigational Site
- 1222.14.4305 Boehringer Ingelheim Investigational Site
- 1222.14.4303 Boehringer Ingelheim Investigational Site
- 1222.14.5301 Boehringer Ingelheim Investigational Site
- 1222.14.5302 Boehringer Ingelheim Investigational Site
- 1222.14.5305 Boehringer Ingelheim Investigational Site
- 1222.14.5306 Boehringer Ingelheim Investigational Site
- 1222.14.5304 Boehringer Ingelheim Investigational Site
- 1222.14.5303 Boehringer Ingelheim Investigational Site
- 1222.14.5701 Boehringer Ingelheim Investigational Site
- 1222.14.5703 Boehringer Ingelheim Investigational Site
- 1222.14.5702 Boehringer Ingelheim Investigational Site
- 1222.14.4802 Boehringer Ingelheim Investigational Site
- 1222.14.4801 Boehringer Ingelheim Investigational Site
- 1222.14.5802 Boehringer Ingelheim Investigational Site
- 1222.14.5803 Boehringer Ingelheim Investigational Site
- 1222.14.5801 Boehringer Ingelheim Investigational Site
- 1222.14.6103 Boehringer Ingelheim Investigational Site
- 1222.14.6102 Boehringer Ingelheim Investigational Site
- 1222.14.6101 Boehringer Ingelheim Investigational Site
- 1222.14.6203 Boehringer Ingelheim Investigational Site
- 1222.14.6201 Boehringer Ingelheim Investigational Site
- 1222.14.6202 Boehringer Ingelheim Investigational Site
- 1222.14.4901 Boehringer Ingelheim Investigational Site
- 1222.14.4902 Boehringer Ingelheim Investigational Site
- 1222.14.4401 Boehringer Ingelheim Investigational Site
- 1222.14.4402 Boehringer Ingelheim Investigational Site
- 1222.14.4406 Boehringer Ingelheim Investigational Site
- 1222.14.4405 Boehringer Ingelheim Investigational Site
- 1222.14.4403 Boehringer Ingelheim Investigational Site
- 1222.14.4407 Boehringer Ingelheim Investigational Site
- 1222.14.4501 Boehringer Ingelheim Investigational Site
- 1222.14.4503 Boehringer Ingelheim Investigational Site
- 1222.14.4502 Boehringer Ingelheim Investigational Site
- 1222.14.5904 Boehringer Ingelheim Investigational Site
- 1222.14.5901 Boehringer Ingelheim Investigational Site
- 1222.14.5902 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 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 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 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 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.
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.
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.
Changes in Safety Parameters Related to Treatment
Occurence of cardiac disorders and investigations related to treatment.
Absolute Plasma Concentrations
Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00796653
Brief Title
Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease II
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
January 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
937 (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 devices for comparison with Olodaterol (BI 1744) on 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 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 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 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 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
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
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
Changes in Safety Parameters Related to Treatment
Description
Occurence of cardiac disorders and investigations related to treatment.
Time Frame
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 study drug administration and 10 minutes post-dose at week 6, 12 and 18
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
1222.14.5004 Boehringer Ingelheim Investigational Site
City
Capital Federal
Country
Argentina
Facility Name
1222.14.5005 Boehringer Ingelheim Investigational Site
City
Florencio Varela
Country
Argentina
Facility Name
1222.14.5003 Boehringer Ingelheim Investigational Site
City
Mar del Plata
Country
Argentina
Facility Name
1222.14.5001 Boehringer Ingelheim Investigational Site
City
Mendoza
Country
Argentina
Facility Name
1222.14.5002 Boehringer Ingelheim Investigational Site
City
Quilmes
Country
Argentina
Facility Name
1222.14.5106 Boehringer Ingelheim Investigational Site
City
Florianopolis
Country
Brazil
Facility Name
1222.14.5101 Boehringer Ingelheim Investigational Site
City
Porto Alegre
Country
Brazil
Facility Name
1222.14.5103 Boehringer Ingelheim Investigational Site
City
Porto Alegre
Country
Brazil
Facility Name
1222.14.5104 Boehringer Ingelheim Investigational Site
City
Porto Alegre
Country
Brazil
Facility Name
1222.14.5102 Boehringer Ingelheim Investigational Site
City
Recife
Country
Brazil
Facility Name
1222.14.5105 Boehringer Ingelheim Investigational Site
City
Sao Paulo
Country
Brazil
Facility Name
1222.14.4005 Boehringer Ingelheim Investigational Site
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
1222.14.4002 Boehringer Ingelheim Investigational Site
City
Kelowna
State/Province
British Columbia
Country
Canada
Facility Name
1222.14.4004 Boehringer Ingelheim Investigational Site
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
1222.14.4009 Boehringer Ingelheim Investigational Site
City
Moncton
State/Province
New Brunswick
Country
Canada
Facility Name
1222.14.4010 Boehringer Ingelheim Investigational Site
City
St. John's
State/Province
Newfoundland and Labrador
Country
Canada
Facility Name
1222.14.4008 Boehringer Ingelheim Investigational Site
City
Grimsby
State/Province
Ontario
Country
Canada
Facility Name
1222.14.4014 Boehringer Ingelheim Investigational Site
City
Mississauga
State/Province
Ontario
Country
Canada
Facility Name
1222.14.4007 Boehringer Ingelheim Investigational Site
City
Newmarket
State/Province
Ontario
Country
Canada
Facility Name
1222.14.4013 Boehringer Ingelheim Investigational Site
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
1222.14.4001 Boehringer Ingelheim Investigational Site
City
Scarborough
State/Province
Ontario
Country
Canada
Facility Name
1222.14.4012 Boehringer Ingelheim Investigational Site
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
1222.14.4015 Boehringer Ingelheim Investigational Site
City
Sherbrooke
State/Province
Quebec
Country
Canada
Facility Name
1222.14.4011 Boehringer Ingelheim Investigational Site
City
Saskatoon
State/Province
Saskatchewan
Country
Canada
Facility Name
1222.14.4006 Boehringer Ingelheim Investigational Site
City
Quebec
Country
Canada
Facility Name
1222.14.6004 Boehringer Ingelheim Investigational Site
City
Brno
Country
Czech Republic
Facility Name
1222.14.6003 Boehringer Ingelheim Investigational Site
City
Hradec Kralove
Country
Czech Republic
Facility Name
1222.14.6002 Boehringer Ingelheim Investigational Site
City
Kyjov
Country
Czech Republic
Facility Name
1222.14.6001 Boehringer Ingelheim Investigational Site
City
Znojmo
Country
Czech Republic
Facility Name
1222.14.4602 Boehringer Ingelheim Investigational Site
City
Helsingør
Country
Denmark
Facility Name
1222.14.4601 Boehringer Ingelheim Investigational Site
City
Hillerød
Country
Denmark
Facility Name
1222.14.4603 Boehringer Ingelheim Investigational Site
City
Roskilde
Country
Denmark
Facility Name
1222.14.4702 Boehringer Ingelheim Investigational Site
City
Espoo
Country
Finland
Facility Name
1222.14.4701 Boehringer Ingelheim Investigational Site
City
HUS
Country
Finland
Facility Name
1222.14.4703 Boehringer Ingelheim Investigational Site
City
Lohja
Country
Finland
Facility Name
1222.14.4106 Boehringer Ingelheim Investigational Site
City
Aschaffenburg
Country
Germany
Facility Name
1222.14.4112 Boehringer Ingelheim Investigational Site
City
Berlin
Country
Germany
Facility Name
1222.14.4103 Boehringer Ingelheim Investigational Site
City
Frankfurt
Country
Germany
Facility Name
1222.14.4110 Boehringer Ingelheim Investigational Site
City
Frankfurt
Country
Germany
Facility Name
1222.14.4108 Boehringer Ingelheim Investigational Site
City
Gelnhausen
Country
Germany
Facility Name
1222.14.4107 Boehringer Ingelheim Investigational Site
City
Kelkheim
Country
Germany
Facility Name
1222.14.4114 Boehringer Ingelheim Investigational Site
City
Lübeck
Country
Germany
Facility Name
1222.14.4111 Boehringer Ingelheim Investigational Site
City
Mainz
Country
Germany
Facility Name
1222.14.4113 Boehringer Ingelheim Investigational Site
City
Minden
Country
Germany
Facility Name
1222.14.4109 Boehringer Ingelheim Investigational Site
City
Mönchengladbach
Country
Germany
Facility Name
1222.14.4104 Boehringer Ingelheim Investigational Site
City
Rodgau-Dudenhofen
Country
Germany
Facility Name
1222.14.4105 Boehringer Ingelheim Investigational Site
City
Wiesloch
Country
Germany
Facility Name
1222.14.5501 Boehringer Ingelheim Investigational Site
City
Hong Kong
Country
Hong Kong
Facility Name
1222.14.5412 Boehringer Ingelheim Investigational Site
City
Coimbatore
Country
India
Facility Name
1222.14.5406 Boehringer Ingelheim Investigational Site
City
Hyderabad
Country
India
Facility Name
1222.14.5402 Boehringer Ingelheim Investigational Site
City
Indore
Country
India
Facility Name
1222.14.5405 Boehringer Ingelheim Investigational Site
City
Jaipur
Country
India
Facility Name
1222.14.5409 Boehringer Ingelheim Investigational Site
City
Jaipur
Country
India
Facility Name
1222.14.5403 Boehringer Ingelheim Investigational Site
City
Mangalore
Country
India
Facility Name
1222.14.5407 Boehringer Ingelheim Investigational Site
City
Mysore
Country
India
Facility Name
1222.14.5404 Boehringer Ingelheim Investigational Site
City
Nagpur
Country
India
Facility Name
1222.14.5408 Boehringer Ingelheim Investigational Site
City
Noida
Country
India
Facility Name
1222.14.5401 Boehringer Ingelheim Investigational Site
City
Pune
Country
India
Facility Name
1222.14.5410 Boehringer Ingelheim Investigational Site
City
Vellore
Country
India
Facility Name
1222.14.4301 Boehringer Ingelheim Investigational Site
City
Cassano Delle Murge (ba)
Country
Italy
Facility Name
1222.14.4302 Boehringer Ingelheim Investigational Site
City
Genova
Country
Italy
Facility Name
1222.14.4304 Boehringer Ingelheim Investigational Site
City
Milano
Country
Italy
Facility Name
1222.14.4305 Boehringer Ingelheim Investigational Site
City
Parma
Country
Italy
Facility Name
1222.14.4303 Boehringer Ingelheim Investigational Site
City
Roma
Country
Italy
Facility Name
1222.14.5301 Boehringer Ingelheim Investigational Site
City
Bucheon
Country
Korea, Republic of
Facility Name
1222.14.5302 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1222.14.5305 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1222.14.5306 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1222.14.5304 Boehringer Ingelheim Investigational Site
City
Uijeongbu
Country
Korea, Republic of
Facility Name
1222.14.5303 Boehringer Ingelheim Investigational Site
City
Wonju
Country
Korea, Republic of
Facility Name
1222.14.5701 Boehringer Ingelheim Investigational Site
City
Georgetown, Pulau Pinang
Country
Malaysia
Facility Name
1222.14.5703 Boehringer Ingelheim Investigational Site
City
Kuala Lumpur
Country
Malaysia
Facility Name
1222.14.5702 Boehringer Ingelheim Investigational Site
City
Kuching, Sarawak
Country
Malaysia
Facility Name
1222.14.4802 Boehringer Ingelheim Investigational Site
City
Fredrikstad
Country
Norway
Facility Name
1222.14.4801 Boehringer Ingelheim Investigational Site
City
SKI
Country
Norway
Facility Name
1222.14.5802 Boehringer Ingelheim Investigational Site
City
Iloilo City
Country
Philippines
Facility Name
1222.14.5803 Boehringer Ingelheim Investigational Site
City
Iloilo City
Country
Philippines
Facility Name
1222.14.5801 Boehringer Ingelheim Investigational Site
City
Manila
Country
Philippines
Facility Name
1222.14.6103 Boehringer Ingelheim Investigational Site
City
Brasov
Country
Romania
Facility Name
1222.14.6102 Boehringer Ingelheim Investigational Site
City
Constanta
Country
Romania
Facility Name
1222.14.6101 Boehringer Ingelheim Investigational Site
City
Iasi
Country
Romania
Facility Name
1222.14.6203 Boehringer Ingelheim Investigational Site
City
Petrozavodsk
Country
Russian Federation
Facility Name
1222.14.6201 Boehringer Ingelheim Investigational Site
City
St. Petersburg
Country
Russian Federation
Facility Name
1222.14.6202 Boehringer Ingelheim Investigational Site
City
St. Petersburg
Country
Russian Federation
Facility Name
1222.14.4901 Boehringer Ingelheim Investigational Site
City
Cape Town
Country
South Africa
Facility Name
1222.14.4902 Boehringer Ingelheim Investigational Site
City
Cape Town
Country
South Africa
Facility Name
1222.14.4401 Boehringer Ingelheim Investigational Site
City
Barcelona
Country
Spain
Facility Name
1222.14.4402 Boehringer Ingelheim Investigational Site
City
Barcelona
Country
Spain
Facility Name
1222.14.4406 Boehringer Ingelheim Investigational Site
City
Madrid
Country
Spain
Facility Name
1222.14.4405 Boehringer Ingelheim Investigational Site
City
Mérida
Country
Spain
Facility Name
1222.14.4403 Boehringer Ingelheim Investigational Site
City
Palma de Mallorca
Country
Spain
Facility Name
1222.14.4407 Boehringer Ingelheim Investigational Site
City
Terrassa (Barcelona)
Country
Spain
Facility Name
1222.14.4501 Boehringer Ingelheim Investigational Site
City
Boden
Country
Sweden
Facility Name
1222.14.4503 Boehringer Ingelheim Investigational Site
City
Göteboerg
Country
Sweden
Facility Name
1222.14.4502 Boehringer Ingelheim Investigational Site
City
Lund
Country
Sweden
Facility Name
1222.14.5904 Boehringer Ingelheim Investigational Site
City
Bangkok
Country
Thailand
Facility Name
1222.14.5901 Boehringer Ingelheim Investigational Site
City
Khon Kaen
Country
Thailand
Facility Name
1222.14.5902 Boehringer Ingelheim Investigational Site
City
Songkla
Country
Thailand
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/1222/1222.14_U10-3195-01-DS.pdf
Description
Related Info
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1222/1222.14_Literature.pdf
Description
Related Info
Learn more about this trial
Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease II
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