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:
NCT01431274
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 Chronic Obstructive Pulmonary Disease (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 1]

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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) 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 1 hr 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 1 hr 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.


  • FVC (Forced Vital Capacity) 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.


  • FVC (Forced Vital Capacity) 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.


  • FVC (Forced Vital Capacity) 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.


  • FVC (Forced Vital Capacity) 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 23 h and at 23 h 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 the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ Time Frame: Day 43 ] [ Designated as safety issue: No ]

    Mahler Transitional Dyspnoea Index (TDI) focal score on Day 43 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).

    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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

    Mahler Transitional Dyspnoea Index (TDI) focal score on Day 85 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).

    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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) [ Time Frame: Day 365 ] [ Designated as safety issue: No ]

    Mahler Transitional Dyspnoea Index (TDI) focal score on Day 365 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).

    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: 2624
Study Start Date: September 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tiotropium+olodaterol low dose FDC
Once daily 2 puffs solution for inhalation Respimat
Drug: tiotropium + olodaterol
fixed dose combination
Device: Respimat
Respimat inhaler
Experimental: tiotropium+olodaterol high 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
Device: Respimat
Respimat inhaler
Active Comparator: tiotropium high dose
Once daily 2 puffs solution for inhalation Respimat
Drug: tiotropium
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: NCT01431274

  Hide Study Locations
Locations
United States, Alabama
1237.5.01038 Boehringer Ingelheim Investigational Site
Jasper, Alabama, United States
1237.5.01036 Boehringer Ingelheim Investigational Site
Mobile, Alabama, United States
United States, Colorado
1237.5.01015 Boehringer Ingelheim Investigational Site
Boulder, Colorado, United States
1237.5.01024 Boehringer Ingelheim Investigational Site
Wheat Ridge, Colorado, United States
United States, Connecticut
1237.5.01034 Boehringer Ingelheim Investigational Site
Stamford, Connecticut, United States
United States, Florida
1237.5.01003 Boehringer Ingelheim Investigational Site
Clearwater, Florida, United States
1237.5.01010 Boehringer Ingelheim Investigational Site
Clearwater, Florida, United States
1237.5.01027 Boehringer Ingelheim Investigational Site
Panama City, Florida, United States
United States, Illinois
1237.5.01031 Boehringer Ingelheim Investigational Site
O'Fallon, Illinois, United States
United States, Louisiana
1237.5.01035 Boehringer Ingelheim Investigational Site
Opelousas, Louisiana, United States
1237.5.01004 Boehringer Ingelheim Investigational Site
Shreveport, Louisiana, United States
United States, Maine
1237.5.01017 Boehringer Ingelheim Investigational Site
Biddeford, Maine, United States
United States, Maryland
1237.5.01028 Boehringer Ingelheim Investigational Site
Columbia, Maryland, United States
United States, Michigan
1237.5.01013 Boehringer Ingelheim Investigational Site
Livonia, Michigan, United States
United States, Nebraska
1237.5.01019 Boehringer Ingelheim Investigational Site
Omaha, Nebraska, United States
United States, New York
1237.5.01025 Boehringer Ingelheim Investigational Site
Larchmont, New York, United States
1237.5.01008 Boehringer Ingelheim Investigational Site
Rochester, New York, United States
United States, North Carolina
1237.5.01023 Boehringer Ingelheim Investigational Site
Raleigh, North Carolina, United States
1237.5.01016 Boehringer Ingelheim Investigational Site
Tabor City, North Carolina, United States
United States, Ohio
1237.5.01006 Boehringer Ingelheim Investigational Site
Cincinnati, Ohio, United States
1237.5.01040 Boehringer Ingelheim Investigational Site
Columbus, Ohio, United States
1237.5.01039 Boehringer Ingelheim Investigational Site
Dayton, Ohio, United States
1237.5.01037 Boehringer Ingelheim Investigational Site
Toledo, Ohio, United States
United States, Oklahoma
1237.5.01009 Boehringer Ingelheim Investigational Site
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
1237.5.01032 Boehringer Ingelheim Investigational Site
Charleston, Pennsylvania, United States
United States, Rhode Island
1237.5.01005 Boehringer Ingelheim Investigational Site
Johnston, Rhode Island, United States
United States, South Carolina
1237.5.01021 Boehringer Ingelheim Investigational Site
Easley, South Carolina, United States
1237.5.01012 Boehringer Ingelheim Investigational Site
Gaffney, South Carolina, United States
1237.5.01014 Boehringer Ingelheim Investigational Site
Spartanburg, South Carolina, United States
United States, Texas
1237.5.01029 Boehringer Ingelheim Investigational Site
Ft. Worth, Texas, United States
1237.5.01002 Boehringer Ingelheim Investigational Site
San Antonio, Texas, United States
United States, Virginia
1237.5.01026 Boehringer Ingelheim Investigational Site
Lynchburg, Virginia, United States
United States, Washington
1237.5.01007 Boehringer Ingelheim Investigational Site
Spokane, Washington, United States
1237.5.01033 Boehringer Ingelheim Investigational Site
Tacoma, Washington, United States
United States, West Virginia
1237.5.01001 Boehringer Ingelheim Investigational Site
Morgantown, West Virginia, United States
Argentina
1237.5.54010 Boehringer Ingelheim Investigational Site
Buenos Aires, Argentina
1237.5.54013 Boehringer Ingelheim Investigational Site
Caba, Argentina
1237.5.54016 Boehringer Ingelheim Investigational Site
Caba, Argentina
1237.5.54003 Boehringer Ingelheim Investigational Site
Capital Federal, Argentina
1237.5.54002 Boehringer Ingelheim Investigational Site
Cuidad Autonoma de Buenos Airess A, Argentina
1237.5.54007 Boehringer Ingelheim Investigational Site
Mar del Plata, Argentina
1237.5.54006 Boehringer Ingelheim Investigational Site
Mar del Plata, Argentina
1237.5.54009 Boehringer Ingelheim Investigational Site
Mendoza, Argentina
1237.5.54012 Boehringer Ingelheim Investigational Site
Monte Grande, Argentina
1237.5.54008 Boehringer Ingelheim Investigational Site
Quilmes, Argentina
1237.5.54005 Boehringer Ingelheim Investigational Site
Rosario, Argentina
1237.5.54004 Boehringer Ingelheim Investigational Site
San Miguel de Tucuma, Argentina
1237.5.54011 Boehringer Ingelheim Investigational Site
San Miguel de Tucuman, Argentina
Australia, South Australia
1237.5.61001 Boehringer Ingelheim Investigational Site
Toorak Gardens, South Australia, Australia
1237.5.61002 Boehringer Ingelheim Investigational Site
Woodville, South Australia, Australia
Australia, Victoria
1237.5.61004 Boehringer Ingelheim Investigational Site
Frankston, Victoria, Australia
Bulgaria
1237.5.35905 Boehringer Ingelheim Investigational Site
Plovdiv, Bulgaria
1237.5.35901 Boehringer Ingelheim Investigational Site
Rousse, Bulgaria
1237.5.35906 Boehringer Ingelheim Investigational Site
Shumen, Bulgaria
1237.5.35904 Boehringer Ingelheim Investigational Site
Sofia, Bulgaria
1237.5.35902 Boehringer Ingelheim Investigational Site
Sofia, Bulgaria
1237.5.35903 Boehringer Ingelheim Investigational Site
Troyan, Bulgaria
1237.5.35908 Boehringer Ingelheim Investigational Site
Veliko Tarnovo, Bulgaria
Canada, Alberta
1237.5.02002 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
Canada, British Columbia
1237.5.02001 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
Canada, Manitoba
1237.5.02004 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba, Canada
Canada, Ontario
1237.5.02005 Boehringer Ingelheim Investigational Site
Burlington, Ontario, Canada
1237.5.02007 Boehringer Ingelheim Investigational Site
Grimsby, Ontario, Canada
1237.5.02011 Boehringer Ingelheim Investigational Site
Ottawa, Ontario, Canada
Canada, Quebec
1237.5.02008 Boehringer Ingelheim Investigational Site
Sherbrooke, Quebec, Canada
Canada, Saskatchewan
1237.5.02009 Boehringer Ingelheim Investigational Site
Saskatoon, Saskatchewan, Canada
Canada
1237.5.02003 Boehringer Ingelheim Investigational Site
Quebec, Canada
1237.5.02006 Boehringer Ingelheim Investigational Site
Quebec, Canada
China
1237.5.86004 Boehringer Ingelheim Investigational Site
Beijing, China
1237.5.86003 Boehringer Ingelheim Investigational Site
Beijing, China
1237.5.86011 Boehringer Ingelheim Investigational Site
Changsha, China
1237.5.86012 Boehringer Ingelheim Investigational Site
Changsha, China
1237.5.86014 Boehringer Ingelheim Investigational Site
Foshan, China
1237.5.86001 Boehringer Ingelheim Investigational Site
Guangzhou, China
1237.5.86015 Boehringer Ingelheim Investigational Site
Nan Ning, China
1237.5.86005 Boehringer Ingelheim Investigational Site
Shanghai, China
1237.5.86002 Boehringer Ingelheim Investigational Site
Shanghai, China
1237.5.86006 Boehringer Ingelheim Investigational Site
Shanghai, China
1237.5.86007 Boehringer Ingelheim Investigational Site
Shanghai, China
1237.5.86009 Boehringer Ingelheim Investigational Site
Shenyang, China
1237.5.86016 Boehringer Ingelheim Investigational Site
Wuhan, China
1237.5.86010 Boehringer Ingelheim Investigational Site
Xi'An, China
1237.5.86008 Boehringer Ingelheim Investigational Site
Yangzhou, China
1237.5.86017 Boehringer Ingelheim Investigational Site
Yinchuan, China
Czech Republic
1237.5.42004 Boehringer Ingelheim Investigational Site
Beroun, Czech Republic
1237.5.42002 Boehringer Ingelheim Investigational Site
Cvikov, Czech Republic
1237.5.42001 Boehringer Ingelheim Investigational Site
Praha 6, Czech Republic
1237.5.42005 Boehringer Ingelheim Investigational Site
Rokycany, Czech Republic
1237.5.42003 Boehringer Ingelheim Investigational Site
Znojmo, Czech Republic
Denmark
1237.5.45002 Boehringer Ingelheim Investigational Site
Aalborg, Denmark
1237.5.45009 Boehringer Ingelheim Investigational Site
Hvidovre, Denmark
1237.5.45007 Boehringer Ingelheim Investigational Site
Kolding, Denmark
1237.5.45001 Boehringer Ingelheim Investigational Site
København NV, Denmark
1237.5.45011 Boehringer Ingelheim Investigational Site
Næstved, Denmark
1237.5.45006 Boehringer Ingelheim Investigational Site
Odense C, Denmark
1237.5.45008 Boehringer Ingelheim Investigational Site
Roskilde, Denmark
1237.5.45003 Boehringer Ingelheim Investigational Site
Silkeborg, Denmark
1237.5.45005 Boehringer Ingelheim Investigational Site
Sønderborg, Denmark
1237.5.45004 Boehringer Ingelheim Investigational Site
Vaerløse, Denmark
Estonia
1237.5.37002 Boehringer Ingelheim Investigational Site
Tallin, Estonia
1237.5.37001 Boehringer Ingelheim Investigational Site
Tartu, Estonia
Finland
1237.5.35801 Boehringer Ingelheim Investigational Site
Helsinki, Finland
1237.5.35804 Boehringer Ingelheim Investigational Site
Pori, Finland
1237.5.35802 Boehringer Ingelheim Investigational Site
Turku, Finland
France
1237.5.33004 Boehringer Ingelheim Investigational Site
Bethune Cedex, France
1237.5.33007 Boehringer Ingelheim Investigational Site
Montpellier cedex 5, France
1237.5.33005 Boehringer Ingelheim Investigational Site
Nantes, France
1237.5.33006 Boehringer Ingelheim Investigational Site
Nîmes cedex 9, France
1237.5.33008 Boehringer Ingelheim Investigational Site
Perpignan, France
1237.5.33001 Boehringer Ingelheim Investigational Site
Saint Pierre Cedex, France
1237.5.33002 Boehringer Ingelheim Investigational Site
Strasbourg, France
Germany
1237.5.49006 Boehringer Ingelheim Investigational Site
Bamberg, Germany
1237.5.49002 Boehringer Ingelheim Investigational Site
Berlin, Germany
1237.5.49003 Boehringer Ingelheim Investigational Site
Berlin, Germany
1237.5.49013 Boehringer Ingelheim Investigational Site
Berlin, Germany
1237.5.49011 Boehringer Ingelheim Investigational Site
Erfurt, Germany
1237.5.49005 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1237.5.49010 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1237.5.49009 Boehringer Ingelheim Investigational Site
Koblenz, Germany
1237.5.49014 Boehringer Ingelheim Investigational Site
Neu-Isenburg, Germany
1237.5.49012 Boehringer Ingelheim Investigational Site
Oschersleben, Germany
1237.5.49001 Boehringer Ingelheim Investigational Site
Rüdersdorf, Germany
1237.5.49004 Boehringer Ingelheim Investigational Site
Weinheim, Germany
1237.5.49008 Boehringer Ingelheim Investigational Site
Wiesloch, Germany
Guatemala
1237.5.50203 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1237.5.50202 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1237.5.50207 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1237.5.50204 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1237.5.50205 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1237.5.50201 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
1237.5.50206 Boehringer Ingelheim Investigational Site
Guatemala, Guatemala
Hungary
1237.5.36005 Boehringer Ingelheim Investigational Site
Debrecen, Hungary
1237.5.36001 Boehringer Ingelheim Investigational Site
Deszk, Hungary
1237.5.36006 Boehringer Ingelheim Investigational Site
Kapuvar, Hungary
1237.5.36003 Boehringer Ingelheim Investigational Site
Szombathely, Hungary
1237.5.36002 Boehringer Ingelheim Investigational Site
Törökbalint, Hungary
India
1237.5.91010 Boehringer Ingelheim Investigational Site
Ahmedabad, India
1237.5.91002 Boehringer Ingelheim Investigational Site
Bangalore, India
1237.5.91007 Boehringer Ingelheim Investigational Site
Bangalore, India
1237.5.91004 Boehringer Ingelheim Investigational Site
Coimbatore, India
1237.5.91011 Boehringer Ingelheim Investigational Site
Hyderabad, India
1237.5.91001 Boehringer Ingelheim Investigational Site
Jaipur, India
1237.5.91008 Boehringer Ingelheim Investigational Site
Jaipur, India
1237.5.91009 Boehringer Ingelheim Investigational Site
Mysore, India
1237.5.91006 Boehringer Ingelheim Investigational Site
Pune, India
Italy
1237.5.39008 Boehringer Ingelheim Investigational Site
Cagliari, Italy
1237.5.39002 Boehringer Ingelheim Investigational Site
Genova, Italy
1237.5.39006 Boehringer Ingelheim Investigational Site
Montescano (PV), Italy
1237.5.39009 Boehringer Ingelheim Investigational Site
Monza, Italy
1237.5.39004 Boehringer Ingelheim Investigational Site
Parma, Italy
1237.5.39001 Boehringer Ingelheim Investigational Site
Pisa, Italy
Japan
1237.5.81003 Boehringer Ingelheim Investigational Site
Aoba-ku, Sendai, Miyagi, Japan
1237.5.81001 Boehringer Ingelheim Investigational Site
Asahikawa, Hokkaido, Japan
1237.5.81006 Boehringer Ingelheim Investigational Site
Bunkyo-ku, Tokyo, Japan
1237.5.81044 Boehringer Ingelheim Investigational Site
Chuo-ku, Kumamoto, Kumamoto, Japan
1237.5.81035 Boehringer Ingelheim Investigational Site
Gifu, Gifu, Japan
1237.5.81017 Boehringer Ingelheim Investigational Site
Hakata-ku, Fukuoka, Fukuoka, Japan
1237.5.81031 Boehringer Ingelheim Investigational Site
Hamamatsushi, Shizuoka, Japan
1237.5.81014 Boehringer Ingelheim Investigational Site
Himeji, Hyogo, Japan
1237.5.81037 Boehringer Ingelheim Investigational Site
Ikoma, Nara, Japan
1237.5.81024 Boehringer Ingelheim Investigational Site
Inashiki-gun, Ibaraki, Japan
1237.5.81008 Boehringer Ingelheim Investigational Site
Itabashi-ku, Tokyo, Japan
1237.5.81016 Boehringer Ingelheim Investigational Site
Jonan-ku, Fukuoka, Fukuoka, Japan
1237.5.81021 Boehringer Ingelheim Investigational Site
Kagoshima, Kagoshima, Japan
1237.5.81020 Boehringer Ingelheim Investigational Site
Kagoshima, Kagoshima,, Japan
1237.5.81005 Boehringer Ingelheim Investigational Site
Kamogawa, Chiba, Japan
1237.5.81011 Boehringer Ingelheim Investigational Site
Kishiwada, Osaka, Japan
1237.5.81018 Boehringer Ingelheim Investigational Site
Kitakyusyu,Fukuoka, Japan
1237.5.81042 Boehringer Ingelheim Investigational Site
Koga, Fukuoka, Japan
1237.5.81032 Boehringer Ingelheim Investigational Site
Komaki, Aichi, Japan
1237.5.81033 Boehringer Ingelheim Investigational Site
Komaki, Aichi, Japan
1237.5.81019 Boehringer Ingelheim Investigational Site
Koshi, Kumamoto, Japan
1237.5.81027 Boehringer Ingelheim Investigational Site
koto-ku, Tokyo, Japan
1237.5.81025 Boehringer Ingelheim Investigational Site
Kuki, Saitama, Japan
1237.5.81038 Boehringer Ingelheim Investigational Site
Kure, Hiroshima, Japan
1237.5.81015 Boehringer Ingelheim Investigational Site
Kurume, Fukuoka, Japan
1237.5.81030 Boehringer Ingelheim Investigational Site
Matsumoto, Nagano, Japan
1237.5.81029 Boehringer Ingelheim Investigational Site
Matsumoto, Nagano, Japan
1237.5.81010 Boehringer Ingelheim Investigational Site
Matsusaka, Mie, Japan
1237.5.81041 Boehringer Ingelheim Investigational Site
Minami-ku. Fukuoka, Fukuoka, Japan
1237.5.81002 Boehringer Ingelheim Investigational Site
Morioka, Iwate, Japan
1237.5.81034 Boehringer Ingelheim Investigational Site
Nagoya, Aichi, Japan
1237.5.81036 Boehringer Ingelheim Investigational Site
Nagoya, Aichi, Japan
1237.5.81004 Boehringer Ingelheim Investigational Site
Naka-gun, Ibaraki, Japan
1237.5.81022 Boehringer Ingelheim Investigational Site
Okinawa, Urasoe, Japan
1237.5.81023 Boehringer Ingelheim Investigational Site
Okinawa, Urasoe, Japan
1237.5.81012 Boehringer Ingelheim Investigational Site
Sayama, Osaka, Japan
1237.5.81045 Boehringer Ingelheim Investigational Site
Sendai, Miyagi, Japan
1237.5.81009 Boehringer Ingelheim Investigational Site
Seto, Aichi, Japan
1237.5.81026 Boehringer Ingelheim Investigational Site
Shinagawa, Tokyo, Japan
1237.5.81007 Boehringer Ingelheim Investigational Site
Shinjyuku-ku, Tokyo, Japan
1237.5.81039 Boehringer Ingelheim Investigational Site
Takamatsu, Kagawa, Japan
1237.5.81040 Boehringer Ingelheim Investigational Site
Takamatsu, Kagawa, Japan
1237.5.81013 Boehringer Ingelheim Investigational Site
Wakayama, Wakayama, Japan
1237.5.81043 Boehringer Ingelheim Investigational Site
Yanagawa-shi, Fukuoka,, Japan
1237.5.81028 Boehringer Ingelheim Investigational Site
Yokohama, Kanagawa, Japan
Korea, Republic of
1237.5.82004 Boehringer Ingelheim Investigational Site
Bucheon, Korea, Republic of
1237.5.82008 Boehringer Ingelheim Investigational Site
Daegu, Korea, Republic of
1237.5.82003 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1237.5.82002 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1237.5.82007 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1237.5.82001 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1237.5.82005 Boehringer Ingelheim Investigational Site
Suwon, Korea, Republic of
1237.5.82006 Boehringer Ingelheim Investigational Site
Wonju, Korea, Republic of
Mexico
1237.5.52002 Boehringer Ingelheim Investigational Site
Hermosillo, Mexico
1237.5.52003 Boehringer Ingelheim Investigational Site
Mexico, Mexico
1237.5.52007 Boehringer Ingelheim Investigational Site
Monterrey, Mexico
1237.5.52001 Boehringer Ingelheim Investigational Site
Tijuana, Mexico
Netherlands
1237.5.31004 Boehringer Ingelheim Investigational Site
Almelo, Netherlands
1237.5.31006 Boehringer Ingelheim Investigational Site
Breda, Netherlands
1237.5.31001 Boehringer Ingelheim Investigational Site
Eindhoven, Netherlands
1237.5.31008 Boehringer Ingelheim Investigational Site
Harderwijk, Netherlands
1237.5.31007 Boehringer Ingelheim Investigational Site
Heerlen, Netherlands
1237.5.31010 Boehringer Ingelheim Investigational Site
Hengelo, Netherlands
1237.5.31009 Boehringer Ingelheim Investigational Site
Hoorn, Netherlands
1237.5.31005 Boehringer Ingelheim Investigational Site
Nieuwegein, Netherlands
1237.5.31002 Boehringer Ingelheim Investigational Site
Veldhoven, Netherlands
1237.5.31003 Boehringer Ingelheim Investigational Site
Zutphen, Netherlands
New Zealand
1237.5.64002 Boehringer Ingelheim Investigational Site
Dunedin, New Zealand
1237.5.64001 Boehringer Ingelheim Investigational Site
Greenlane East Auckland NZ, New Zealand
Portugal
1237.5.35105 Boehringer Ingelheim Investigational Site
Amadora, Portugal
1237.5.35101 Boehringer Ingelheim Investigational Site
Coimbra, Portugal
1237.5.35102 Boehringer Ingelheim Investigational Site
Lisboa, Portugal
1237.5.35104 Boehringer Ingelheim Investigational Site
Lisboa, Portugal
1237.5.35103 Boehringer Ingelheim Investigational Site
Porto, Portugal
1237.5.35106 Boehringer Ingelheim Investigational Site
Vila Nova de Gaia, Portugal
1237.5.35107 Boehringer Ingelheim Investigational Site
Viseu, Portugal
Russian Federation
1237.5.07001 Boehringer Ingelheim Investigational Site
Gatchina (Leningradskaya oblast), Russian Federation
1237.5.07003 Boehringer Ingelheim Investigational Site
Kazan, Russian Federation
1237.5.07005 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1237.5.07004 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
1237.5.07002 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
Slovenia
1237.5.38601 Boehringer Ingelheim Investigational Site
Golnik, Slovenia
1237.5.38602 Boehringer Ingelheim Investigational Site
Golnik, Slovenia
Turkey
1237.5.90003 Boehringer Ingelheim Investigational Site
Istanbul, Turkey
1237.5.90004 Boehringer Ingelheim Investigational Site
Istanbul, Turkey
1237.5.90002 Boehringer Ingelheim Investigational Site
Izmir, Turkey
1237.5.90005 Boehringer Ingelheim Investigational Site
Izmit, Turkey
1237.5.90001 Boehringer Ingelheim Investigational Site
Mersin, Turkey
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: NCT01431274     History of Changes
Other Study ID Numbers: 1237.5  2009-010668-40 
Study First Received: September 8, 2011
Results First Received: June 19, 2015
Last Updated: June 19, 2015
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Responsible Ethics Committee
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Denmark: The Danish Health and Medicines Authority
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Agence Nationale sécurité médicament et des produits santé
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Public Health and Social Assistance
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Italy: Ethics Committee
Japan: Ministry of Health, Labor and Welfare
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Medsafe
Portugal: National Pharmacy and Medicines Institute
Russia: Pharmacological Committee, Ministry of Health
Slovenia: Agency for Medicinal Products - Ministry of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Turkey: Ministry of Health
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 July 21, 2016