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Tiotropium +Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01431287
First received: September 8, 2011
Last updated: June 19, 2015
Last verified: June 2015
  Purpose
The overall objective of this study is to assess the efficacy and safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the RESPIMAT Inhaler) compared with the individual components (tiotropium, olodaterol) (delivered by the RESPIMAT Inhaler) in patients with COPD.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: tiotropium + olodaterol
Drug: tiotropium
Drug: olodaterol
Device: Respimat
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Parallel Group Study to Assess the Efficacy and Safety of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (2.5 µg / 5 µg; 5 µg / 5 µg) (Delivered by the Respimat® Inhaler) Compared With the Individual Components (2.5 µg and 5 µg Tiotropium, 5 µg Olodaterol) (Delivered by the Respimat® Inhaler) in Patients With Chronic Obstructive Pulmonary Disease (COPD) [TOnado TM 2]

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169 ] [ Designated as safety issue: No ]

    FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the MMRM model in each treatment group.


  • Trough FEV1 Response on Day 170 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170 ] [ Designated as safety issue: No ]

    Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FEV1 measurements performed at 23 h and at 23 h 50 min after inhalation of study medication at the clinic visit on the previous day.

    Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). [ Time Frame: Day 169 ] [ Designated as safety issue: No ]

    The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.



Secondary Outcome Measures:
  • Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: Day 169 ] [ Designated as safety issue: No ]

    Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) is the key secondary endpoint.

    The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.


  • FEV1 AUC(0-3h) Response on Day 1 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment ] [ Designated as safety issue: No ]

    FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • FEV1 AUC(0-3h) Response on Day 85 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85 ] [ Designated as safety issue: No ]

    FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • FEV1 AUC(0-3h) Response on Day 365 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365 ] [ Designated as safety issue: No ]

    FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FEV1 Response on Day 15 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15 ] [ Designated as safety issue: No ]

    Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FEV1 Response on Day 43 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43 ] [ Designated as safety issue: No ]

    Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FEV1 Response on Day 85 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 85 ] [ Designated as safety issue: No ]

    Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FEV1 Response on Day 169 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 169 ] [ Designated as safety issue: No ]

    Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FEV1 Response on Day 365 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 365 ] [ Designated as safety issue: No ]

    Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 1 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment ] [ Designated as safety issue: No ]

    FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 85 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85 ] [ Designated as safety issue: No ]

    FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 169 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169 ] [ Designated as safety issue: No ]

    FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 365 [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365 ] [ Designated as safety issue: No ]

    FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.

    FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FVC Response on Day 15 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15 ] [ Designated as safety issue: No ]

    Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.


  • Trough FVC Response on Day 43 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43 ] [ Designated as safety issue: No ]

    Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.


  • Trough FVC Response on Day 85 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85 ] [ Designated as safety issue: No ]

    Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.


  • Trough FVC Response on Day 170 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23h and at 23h 50 min after inhalation of study medication on day 170 ] [ Designated as safety issue: No ]

    Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FVC measurements performed at 23h and at 23h 50 min after inhalation of study medication at the clinic visit on the previous day.

    Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.


  • Trough FVC Response on Day 365 [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 365 ] [ Designated as safety issue: No ]

    Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.

    Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.

    The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within−patient errors and Kenward-Roger approximation for denominator degrees of freedom.


  • FEV1 AUC(0-12h) Response in Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169 ] [ Designated as safety issue: No ]

    FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.

    FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.

    Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.


  • FEV1 AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169 ] [ Designated as safety issue: No ]

    FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.

    Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.


  • FVC AUC(0-12h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169 ] [ Designated as safety issue: No ]

    FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.

    FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.


  • FVC AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169 ] [ Designated as safety issue: No ]

    FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.

    FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).

    The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.

    Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.


  • Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

    The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.


  • Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: Day 365 ] [ Designated as safety issue: No ]

    The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.


  • Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: Day 43 ] [ Designated as safety issue: No ]

    Mahler TDI focal score on Day 43 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

    The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.


  • Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

    Mahler TDI focal score on Day 85 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

    The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.


  • Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) [ Time Frame: Day 365 ] [ Designated as safety issue: No ]

    Mahler TDI focal score on Day 365 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

    The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

    Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.



Enrollment: 2539
Study Start Date: September 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tiotropium+olodaterol high dose FDC
Once daily 2 puffs solution for inhalation Respimat
Drug: tiotropium + olodaterol
fixed dose combination
Device: Respimat
Respimat inhaler
Experimental: tiotropium+olodaterol low dose FDC
Once daily 2 puffs solution for inhalation Respimat
Drug: tiotropium + olodaterol
fixed dose combination
Device: Respimat
Respimat inhaler
Active Comparator: olodaterol
Once daily 2 puffs solution for inhalation Respimat
Drug: olodaterol
one dose only
Device: Respimat
Respimat inhaler
Active Comparator: tiotropium low dose
Once daily 2 puffs solution for inhalation Respimat
Drug: tiotropium
low dose or high dose
Device: Respimat
Respimat inhaler
Active Comparator: tiotropium high dose
Once daily 2 puffs solution for inhalation Respimat
Drug: tiotropium
low dose or high dose
Device: Respimat
Respimat inhaler

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of chronic obstructive pulmonary disease.
  2. Relatively stable airway obstruction with post FEV1< 80% predicted normal and post FEV1/FVC <70%.
  3. Male or female patients, 40 years of age or older.
  4. Smoking history of more than 10 pack years.

Exclusion criteria:

  1. Significant disease other than COPD
  2. Clinically relevant abnormal lab values.
  3. History of asthma.
  4. Diagnosis of thyrotoxicosis
  5. Diagnosis of paroxysmal tachycardia
  6. History of myocardial infarction within 1 year of screening visit
  7. Unstable or life-threatening cardiac arrhythmia.
  8. Hospitalization for heart failure within the past year.
  9. Known active tuberculosis.
  10. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
  11. History of life-threatening pulmonary obstruction.
  12. History of cystic fibrosis.
  13. Clinically evident bronchiectasis.
  14. History of significant alcohol or drug abuse.
  15. Thoracotomy with pulmonary resection
  16. Oral ß-adrenergics.
  17. Oral corticosteroid medication at unstable doses
  18. Regular use of daytime oxygen therapy for more than one hour per day
  19. Pulmonary rehabilitation program in the six weeks prior to the screening visit
  20. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
  21. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
  22. Pregnant or nursing women.
  23. Women of childbearing potential not using a highly effective method of birth control
  24. Patients who are unable to comply with pulmonary medication restrictions
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431287

  Hide Study Locations
Locations
United States, California
1237.6.01106 Boehringer Ingelheim Investigational Site
Greer, California, United States
United States, Colorado
1237.6.01120 Boehringer Ingelheim Investigational Site
Fort Collins, Colorado, United States
United States, Connecticut
1237.6.01131 Boehringer Ingelheim Investigational Site
Danbury, Connecticut, United States
1237.6.01117 Boehringer Ingelheim Investigational Site
Waterbury, Connecticut, United States
United States, Florida
1237.6.01118 Boehringer Ingelheim Investigational Site
Deland, Florida, United States
1237.6.01126 Boehringer Ingelheim Investigational Site
Tampa, Florida, United States
1237.6.01109 Boehringer Ingelheim Investigational Site
Winter Park, Florida, United States
United States, Georgia
1237.6.01134 Boehringer Ingelheim Investigational Site
Atlanta, Georgia, United States
United States, Idaho
1237.6.01107 Boehringer Ingelheim Investigational Site
Couer d'Alene, Idaho, United States
United States, Louisiana
1237.6.01110 Boehringer Ingelheim Investigational Site
Lafayette, Louisiana, United States
United States, Maryland
1237.6.01128 Boehringer Ingelheim Investigational Site
Baltimore, Maryland, United States
United States, Massachusetts
1237.6.01130 Boehringer Ingelheim Investigational Site
North Dartmouth, Massachusetts, United States
United States, Minnesota
1237.6.01104 Boehringer Ingelheim Investigational Site
Minneapolis, Minnesota, United States
1237.6.01116 Boehringer Ingelheim Investigational Site
Plymouth, Minnesota, United States
United States, Missouri
1237.6.01121 Boehringer Ingelheim Investigational Site
St. Louis, Missouri, United States
1237.6.01123 Boehringer Ingelheim Investigational Site
St. Louis, Missouri, United States
United States, Nevada
1237.6.01129 Boehringer Ingelheim Investigational Site
Henderson, Nevada, United States
United States, New Jersey
1237.6.01136 Boehringer Ingelheim Investigational Site
Marlton, New Jersey, United States
United States, New Mexico
1237.6.01108 Boehringer Ingelheim Investigational Site
Albuquerque, New Mexico, United States
United States, New York
1237.6.01127 Boehringer Ingelheim Investigational Site
Bayside, New York, United States
1237.6.01139 Boehringer Ingelheim Investigational Site
Great Neck, New York, United States
United States, North Carolina
1237.6.01135 Boehringer Ingelheim Investigational Site
Charlotte, North Carolina, United States
United States, Ohio
1237.6.01114 Boehringer Ingelheim Investigational Site
Cincinnati, Ohio, United States
1237.6.01102 Boehringer Ingelheim Investigational Site
Columbus, Ohio, United States
United States, Oklahoma
1237.6.01115 Boehringer Ingelheim Investigational Site
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
1237.6.01101 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
United States, Rhode Island
1237.6.01113 Boehringer Ingelheim Investigational Site
East Providence, Rhode Island, United States
United States, South Carolina
1237.6.01122 Boehringer Ingelheim Investigational Site
Charleston, South Carolina, United States
1237.6.01132 Boehringer Ingelheim Investigational Site
Greenville, South Carolina, United States
1237.6.01137 Boehringer Ingelheim Investigational Site
Greenville, South Carolina, United States
1237.6.01111 Boehringer Ingelheim Investigational Site
Spartanburg, South Carolina, United States
1237.6.01105 Boehringer Ingelheim Investigational Site
Union, South Carolina, United States
United States, Texas
1237.6.01138 Boehringer Ingelheim Investigational Site
Killeen, Texas, United States
1237.6.01124 Boehringer Ingelheim Investigational Site
McKinney, Texas, United States
United States, Virginia
1237.6.01112 Boehringer Ingelheim Investigational Site
Richmond, Virginia, United States
1237.6.01133 Boehringer Ingelheim Investigational Site
Richmond, Virginia, United States
United States, Washington
1237.6.01125 Boehringer Ingelheim Investigational Site
Spokane, Washington, United States
1237.6.01103 Boehringer Ingelheim Investigational Site
Tacoma, Washington, United States
Austria
1237.6.43006 Boehringer Ingelheim Investigational Site
Feldbach, Austria
1237.6.43005 Boehringer Ingelheim Investigational Site
Gänserndorf, Austria
1237.6.43002 Boehringer Ingelheim Investigational Site
Innsbruck, Austria
1237.6.43004 Boehringer Ingelheim Investigational Site
Leoben, Austria
1237.6.43001 Boehringer Ingelheim Investigational Site
Linz, Austria
1237.6.43003 Boehringer Ingelheim Investigational Site
Salzburg, Austria
Belgium
1237.6.32007 Boehringer Ingelheim Investigational Site
Brussel, Belgium
1237.6.32005 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1237.6.32004 Boehringer Ingelheim Investigational Site
Gent, Belgium
1237.6.32002 Boehringer Ingelheim Investigational Site
Jambes, Belgium
1237.6.32009 Boehringer Ingelheim Investigational Site
Lebbeke, Belgium
1237.6.32001 Boehringer Ingelheim Investigational Site
Leuven, Belgium
1237.6.32006 Boehringer Ingelheim Investigational Site
Liège, Belgium
1237.6.32008 Boehringer Ingelheim Investigational Site
Oostende, Belgium
1237.6.32010 Boehringer Ingelheim Investigational Site
Turnhout, Belgium
Brazil
1237.6.55013 Boehringer Ingelheim Investigational Site
Botucatu, Brazil
1237.6.55010 Boehringer Ingelheim Investigational Site
Florianopolis, Brazil
1237.6.55012 Boehringer Ingelheim Investigational Site
Passo Fundo, Brazil
1237.6.55001 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
1237.6.55002 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
1237.6.55003 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
1237.6.55005 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
1237.6.55009 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
1237.6.55006 Boehringer Ingelheim Investigational Site
Sao Paulo, Brazil
1237.6.55007 Boehringer Ingelheim Investigational Site
Sao Paulo, Brazil
1237.6.55011 Boehringer Ingelheim Investigational Site
Sao Paulo, Brazil
Canada, Alberta
1237.6.02109 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
Canada, British Columbia
1237.6.02111 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
Canada, New Brunswick
1237.6.02106 Boehringer Ingelheim Investigational Site
Moncton, New Brunswick, Canada
Canada, Ontario
1237.6.02110 Boehringer Ingelheim Investigational Site
Courtice, Ontario, Canada
1237.6.02101 Boehringer Ingelheim Investigational Site
Downsview, Ontario, Canada
1237.6.02112 Boehringer Ingelheim Investigational Site
Sarnia, Ontario, Canada
1237.6.02103 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
1237.6.02102 Boehringer Ingelheim Investigational Site
Windsor, Ontario, Canada
Canada, Quebec
1237.6.02104 Boehringer Ingelheim Investigational Site
Point Claire, Quebec, Canada
1237.6.02105 Boehringer Ingelheim Investigational Site
Sherbrooke, Quebec, Canada
1237.6.02108 Boehringer Ingelheim Investigational Site
Ste-Foy, Quebec, Canada
China
1237.6.86117 Boehringer Ingelheim Investigational Site
Baotou, China
1237.6.86102 Boehringer Ingelheim Investigational Site
Beijing, China
1237.6.86104 Boehringer Ingelheim Investigational Site
Beijing, China
1237.6.86105 Boehringer Ingelheim Investigational Site
Beijing, China
1237.6.86115 Boehringer Ingelheim Investigational Site
Changsha, China
1237.6.86110 Boehringer Ingelheim Investigational Site
Chengdu, China
1237.6.86111 Boehringer Ingelheim Investigational Site
Chongqing, China
1237.6.86109 Boehringer Ingelheim Investigational Site
Haikou, China
1237.6.86108 Boehringer Ingelheim Investigational Site
Hangzhou, China
1237.6.86116 Boehringer Ingelheim Investigational Site
Hohhot, China
1237.6.86114 Boehringer Ingelheim Investigational Site
Jinan, China
1237.6.86106 Boehringer Ingelheim Investigational Site
Nanjing, China
1237.6.86101 Boehringer Ingelheim Investigational Site
Shanghai, China
1237.6.86113 Boehringer Ingelheim Investigational Site
Shenyang, China
1237.6.86107 Boehringer Ingelheim Investigational Site
Suzhou, China
1237.6.86112 Boehringer Ingelheim Investigational Site
Xi'An, China
Colombia
1237.6.57001 Boehringer Ingelheim Investigational Site
Bogota DC, Colombia
1237.6.57003 Boehringer Ingelheim Investigational Site
Bogota DC, Colombia
1237.6.57007 Boehringer Ingelheim Investigational Site
Bogota DC, Colombia
1237.6.57008 Boehringer Ingelheim Investigational Site
Bogota, Colombia
1237.6.57006 Boehringer Ingelheim Investigational Site
Cali, Colombia
1237.6.57004 Boehringer Ingelheim Investigational Site
Floridablanca, Colombia
Croatia
1237.6.38503 Boehringer Ingelheim Investigational Site
Petrinja, Croatia
1237.6.38504 Boehringer Ingelheim Investigational Site
Rijeka, Croatia
1237.6.38502 Boehringer Ingelheim Investigational Site
Zadar, Croatia
1237.6.38501 Boehringer Ingelheim Investigational Site
Zagreb, Croatia
Germany
1237.6.49022 Boehringer Ingelheim Investigational Site
Aschaffenburg, Germany
1237.6.49017 Boehringer Ingelheim Investigational Site
Berlin, Germany
1237.6.49026 Boehringer Ingelheim Investigational Site
Frankfurt, Germany
1237.6.49027 Boehringer Ingelheim Investigational Site
Frankfurt, Germany
1237.6.49025 Boehringer Ingelheim Investigational Site
Großhansdorf, Germany
1237.6.49016 Boehringer Ingelheim Investigational Site
Halle, Germany
1237.6.49024 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1237.6.49021 Boehringer Ingelheim Investigational Site
Hannover, Germany
1237.6.49019 Boehringer Ingelheim Investigational Site
Leipzig, Germany
1237.6.49028 Boehringer Ingelheim Investigational Site
Mainz, Germany
1237.6.49018 Boehringer Ingelheim Investigational Site
Rodgau/Dudenhofen, Germany
1237.6.49020 Boehringer Ingelheim Investigational Site
Schwerin, Germany
1237.6.49023 Boehringer Ingelheim Investigational Site
Teuchern, Germany
Hungary
1237.6.36001 Boehringer Ingelheim Investigational Site
Debrecen, Hungary
1237.6.36004 Boehringer Ingelheim Investigational Site
Gödöllö, Hungary
1237.6.36005 Boehringer Ingelheim Investigational Site
Pecs, Hungary
1237.6.36003 Boehringer Ingelheim Investigational Site
Sopron, Hungary
1237.6.36002 Boehringer Ingelheim Investigational Site
Szeged, Hungary
India
1237.6.91003 Boehringer Ingelheim Investigational Site
Chennai, India
1237.6.91011 Boehringer Ingelheim Investigational Site
Coimbatore, India
1237.6.91004 Boehringer Ingelheim Investigational Site
Jaipur, India
1237.6.91002 Boehringer Ingelheim Investigational Site
Kolkatta, India
1237.6.91007 Boehringer Ingelheim Investigational Site
Maharastra, India
1237.6.91006 Boehringer Ingelheim Investigational Site
Mumbai, India
1237.6.91009 Boehringer Ingelheim Investigational Site
Nashik, Maharashtra, India
1237.6.91008 Boehringer Ingelheim Investigational Site
Pune, India
Ireland
1237.6.35304 Boehringer Ingelheim Investigational Site
County Limerick, Ireland
1237.6.35303 Boehringer Ingelheim Investigational Site
Dublin 24, Ireland
1237.6.35301 Boehringer Ingelheim Investigational Site
Dublin 4, Ireland
Japan
1237.6.81127 Boehringer Ingelheim Investigational Site
Abeno-ku, Osaka, Osaka, Japan
1237.6.81123 Boehringer Ingelheim Investigational Site
Aoi-ku, Shizuoka, Shizuoka, Japan
1237.6.81132 Boehringer Ingelheim Investigational Site
Chuo-ku, Kobe, Hyogo, Japan
1237.6.81121 Boehringer Ingelheim Investigational Site
Fukui, Fukui, Japan
1237.6.81137 Boehringer Ingelheim Investigational Site
Fukuyama, Hiroshima, Japan
1237.6.81109 Boehringer Ingelheim Investigational Site
Hachioji, Tokyo, Japan
1237.6.81134 Boehringer Ingelheim Investigational Site
Himeji, Hyogo, Japan
1237.6.81106 Boehringer Ingelheim Investigational Site
Hitachi, Ibaraki, Japan
1237.6.81139 Boehringer Ingelheim Investigational Site
Iizuka, Fukuoka, Japan
1237.6.81102 Boehringer Ingelheim Investigational Site
Iwamizawa, Hokkaido, Japan
1237.6.81117 Boehringer Ingelheim Investigational Site
Kamakura, Kanagawa, Japan
1237.6.81120 Boehringer Ingelheim Investigational Site
Kanazawa, Ishikawa, Japan
1237.6.81113 Boehringer Ingelheim Investigational Site
Kanazawa, Yokohama, Kanagawa, Japan
1237.6.81108 Boehringer Ingelheim Investigational Site
Kashiwa, Chiba, Japan
1237.6.81114 Boehringer Ingelheim Investigational Site
Kawasaki-ku, Kawasaki, Kanagawa, Japan
1237.6.81135 Boehringer Ingelheim Investigational Site
Kita-ku, Okayama, Okayama, Japan
1237.6.81126 Boehringer Ingelheim Investigational Site
Kita-ku, Sakai, Osaka, Japan
1237.6.81101 Boehringer Ingelheim Investigational Site
Kita-ku, Sapporo, Hokkaido, Japan
1237.6.81136 Boehringer Ingelheim Investigational Site
Kurashiki, Okayama, Japan
1237.6.81116 Boehringer Ingelheim Investigational Site
Minami-ku, Yokohama, Kanagawa, Japan
1237.6.81118 Boehringer Ingelheim Investigational Site
Minami-ku, Yokohama, Kanagawa, Japan
1237.6.81112 Boehringer Ingelheim Investigational Site
Mitaka, Tokyo, Japan
1237.6.81105 Boehringer Ingelheim Investigational Site
Mito, Ibaraki, Japan
1237.6.81142 Boehringer Ingelheim Investigational Site
Naha, Okinawa, Japan
1237.6.81131 Boehringer Ingelheim Investigational Site
Nishi-ku, Kobe, Hyogo, Japan
1237.6.81104 Boehringer Ingelheim Investigational Site
Obihiro, Hokkaido, Japan
1237.6.81141 Boehringer Ingelheim Investigational Site
Okinawa, Okinawa, Japan
1237.6.81110 Boehringer Ingelheim Investigational Site
Ota-ku, Tokyo, Japan
1237.6.81138 Boehringer Ingelheim Investigational Site
Sakaide, Kagawa, Japan
1237.6.81103 Boehringer Ingelheim Investigational Site
Sapporo, Hokkaido, Japan
1237.6.81140 Boehringer Ingelheim Investigational Site
Shimajiri-gun, Okinawa, Japan
1237.6.81144 Boehringer Ingelheim Investigational Site
Shimajiri-gun, Okinawa, Japan
1237.6.81111 Boehringer Ingelheim Investigational Site
Shinjuku-ku, Tokyo, Japan
1237.6.81145 Boehringer Ingelheim Investigational Site
Shinjuku-ku, Tokyo, Japan
1237.6.81107 Boehringer Ingelheim Investigational Site
Soka, Saitama, Japan
1237.6.81133 Boehringer Ingelheim Investigational Site
Takarazuka, Hyogo, Japan
1237.6.81122 Boehringer Ingelheim Investigational Site
Takayama, Gifu, Japan
1237.6.81143 Boehringer Ingelheim Investigational Site
Tomigusuku, Okinawa, Japan
1237.6.81128 Boehringer Ingelheim Investigational Site
Toyonaka, Osaka, Japan
1237.6.81124 Boehringer Ingelheim Investigational Site
Uji, Kyoto, Japan
1237.6.81130 Boehringer Ingelheim Investigational Site
Yabu, Hyogo, Japan
1237.6.81129 Boehringer Ingelheim Investigational Site
Yao, Osaka, Japan
1237.6.81119 Boehringer Ingelheim Investigational Site
Yokosuka, Kanagawa, Japan
Norway
1237.6.47005 Boehringer Ingelheim Investigational Site
Elverum, Norway
1237.6.47001 Boehringer Ingelheim Investigational Site
Hønefoss, Norway
1237.6.47002 Boehringer Ingelheim Investigational Site
Kløfta, Norway
1237.6.47004 Boehringer Ingelheim Investigational Site
Lierskogen, Norway
1237.6.47003 Boehringer Ingelheim Investigational Site
Oslo, Norway
1237.6.47007 Boehringer Ingelheim Investigational Site
SKI, Norway
1237.6.47008 Boehringer Ingelheim Investigational Site
Svelvik, Norway
Romania
1237.6.40004 Boehringer Ingelheim Investigational Site
Arad, Romania
1237.6.40005 Boehringer Ingelheim Investigational Site
Arad, Romania
1237.6.40001 Boehringer Ingelheim Investigational Site
Bucharest, Romania
1237.6.40002 Boehringer Ingelheim Investigational Site
Bucuresti, Romania
1237.6.40003 Boehringer Ingelheim Investigational Site
Cluj, Romania
Russian Federation
1237.6.07004 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1237.6.07005 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1237.6.07002 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1237.6.07003 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1237.6.07001 Boehringer Ingelheim Investigational Site
Yaroslavl, Russian Federation
Serbia
1237.6.38103 Boehringer Ingelheim Investigational Site
Belgrade, Serbia
1237.6.38104 Boehringer Ingelheim Investigational Site
Belgrade, Serbia
1237.6.38105 Boehringer Ingelheim Investigational Site
Belgrade, Serbia
1237.6.38102 Boehringer Ingelheim Investigational Site
Kragujevac, Serbia
1237.6.38101 Boehringer Ingelheim Investigational Site
Nis, Serbia
Slovakia
1237.6.42101 Boehringer Ingelheim Investigational Site
Bardejov, Slovakia
1237.6.42102 Boehringer Ingelheim Investigational Site
Bojnice, Slovakia
1237.6.42104 Boehringer Ingelheim Investigational Site
Kosice, Slovakia
1237.6.42107 Boehringer Ingelheim Investigational Site
Nitra, Slovakia
1237.6.42103 Boehringer Ingelheim Investigational Site
Spisska Nova Ves, Slovakia
1237.6.42106 Boehringer Ingelheim Investigational Site
Zilina, Slovakia
South Africa
1237.6.27002 Boehringer Ingelheim Investigational Site
Bellville, South Africa
1237.6.27001 Boehringer Ingelheim Investigational Site
Cape Town, South Africa
1237.6.27003 Boehringer Ingelheim Investigational Site
Cape Town, South Africa
1237.6.27004 Boehringer Ingelheim Investigational Site
Cape Town, South Africa
1237.6.27005 Boehringer Ingelheim Investigational Site
Pretoria, South Africa
Spain
1237.6.34008 Boehringer Ingelheim Investigational Site
Badalona (Barcelona), Spain
1237.6.34003 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1237.6.34009 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1237.6.34001 Boehringer Ingelheim Investigational Site
Hospitalet de Llobregat, Spain
1237.6.34002 Boehringer Ingelheim Investigational Site
Mérida, Spain
1237.6.34005 Boehringer Ingelheim Investigational Site
Pozuelo de Alarcón, Spain
1237.6.34004 Boehringer Ingelheim Investigational Site
San Juan de Alicante, Spain
1237.6.34006 Boehringer Ingelheim Investigational Site
Vic (Barcelona), Spain
Sweden
1237.6.46003 Boehringer Ingelheim Investigational Site
Boden, Sweden
1237.6.46002 Boehringer Ingelheim Investigational Site
Göteborg, Sweden
1237.6.46006 Boehringer Ingelheim Investigational Site
Härnösand, Sweden
1237.6.46005 Boehringer Ingelheim Investigational Site
Höllviken, Sweden
1237.6.46001 Boehringer Ingelheim Investigational Site
Lund, Sweden
1237.6.46004 Boehringer Ingelheim Investigational Site
Stockholm, Sweden
1237.6.46007 Boehringer Ingelheim Investigational Site
Uddevalla, Sweden
Taiwan
1237.6.88607 Boehringer Ingelheim Investigational Site
Kaohsiung City, Taiwan
1237.6.88608 Boehringer Ingelheim Investigational Site
Kaohsiung, Taiwan
1237.6.88602 Boehringer Ingelheim Investigational Site
New Taipei City, Taiwan
1237.6.88604 Boehringer Ingelheim Investigational Site
Taichung, Taiwan
1237.6.88605 Boehringer Ingelheim Investigational Site
Tainan, Taiwan
1237.6.88601 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1237.6.88603 Boehringer Ingelheim Investigational Site
Taoyuan County, Taiwan
Turkey
1237.6.90105 Boehringer Ingelheim Investigational Site
Ankara, Turkey
1237.6.90103 Boehringer Ingelheim Investigational Site
Denizli, Turkey
1237.6.90104 Boehringer Ingelheim Investigational Site
Istanbul, Turkey
1237.6.90101 Boehringer Ingelheim Investigational Site
Izmir, Turkey
1237.6.90102 Boehringer Ingelheim Investigational Site
Izmir, Turkey
United Kingdom
1237.6.44002 Boehringer Ingelheim Investigational Site
Blackpool, United Kingdom
1237.6.44009 Boehringer Ingelheim Investigational Site
Blackpool, United Kingdom
1237.6.44007 Boehringer Ingelheim Investigational Site
Bristol, United Kingdom
1237.6.44010 Boehringer Ingelheim Investigational Site
Chertsey, United Kingdom
1237.6.44011 Boehringer Ingelheim Investigational Site
Fleetwood, United Kingdom
1237.6.44001 Boehringer Ingelheim Investigational Site
Manchester, United Kingdom
1237.6.44008 Boehringer Ingelheim Investigational Site
Midsomer Norton, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01431287     History of Changes
Other Study ID Numbers: 1237.6  2009-010669-22 
Study First Received: September 8, 2011
Results First Received: June 19, 2015
Last Updated: June 19, 2015
Health Authority: Austria: Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
China: Food and Drug Administration
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Croatia: Agency for Medicinal Product and Medical Devices
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Ireland: Irish Medicines Board
Japan: Ministry of Health, Labor and Welfare
Mexico: Federal Commission for Protection Against Health Risks
Norway: Norwegian Medicines Agency
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Tiotropium Bromide
Olodaterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on September 28, 2016