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

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

tiotropium + olodaterol

tiotropium

olodaterol

tiotropium

tiotropium + olodaterol

Respimat

About this trial

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

Eligibility Criteria

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

Inclusion criteria:

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

Exclusion criteria:

Significant disease other than COPD
Clinically relevant abnormal lab values.
History of asthma.
Diagnosis of thyrotoxicosis
Diagnosis of paroxysmal tachycardia
History of myocardial infarction within 1 year of screening visit
Unstable or life-threatening cardiac arrhythmia.
Hospitalization for heart failure within the past year.
Known active tuberculosis.
Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
History of life-threatening pulmonary obstruction.
History of cystic fibrosis.
Clinically evident bronchiectasis.
History of significant alcohol or drug abuse.
Thoracotomy with pulmonary resection
Oral ß-adrenergics.
Oral corticosteroid medication at unstable doses
Regular use of daytime oxygen therapy for more than one hour per day
Pulmonary rehabilitation program in the six weeks prior to the screening visit
Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
Pregnant or nursing women.
Women of childbearing potential not using a highly effective method of birth control
Patients who are unable to comply with pulmonary medication restrictions

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Arm Label

tiotropium+olodaterol low dose FDC

tiotropium+olodaterol high dose FDC

olodaterol

tiotropium low dose

tiotropium high dose

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Outcomes

Primary Outcome Measures

Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.

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.

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)

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)

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

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

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

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.

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

Trough FEV1 Response on Day 85

Trough FEV1 Response on Day 169

Trough FEV1 Response on Day 365

FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1

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

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

FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365

Trough FVC Response on Day 15.

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.

Trough FVC Response on Day 85.

Trough FVC Response on Day 170.

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.

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)

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)

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)

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)

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)

Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

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)

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)

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.

Full Information

NCT ID

NCT01431274

First Posted

September 8, 2011

Last Updated

June 19, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01431274

Brief Title

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

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]

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

September 2011 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

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

Pulmonary Disease, Chronic Obstructive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

2624 (Actual)

8. Arms, Groups, and Interventions

Arm Title

tiotropium+olodaterol low dose FDC

Arm Type

Experimental

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Arm Title

tiotropium+olodaterol high dose FDC

Arm Type

Experimental

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Arm Title

olodaterol

Arm Type

Active Comparator

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Arm Title

tiotropium low dose

Arm Type

Active Comparator

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Arm Title

tiotropium high dose

Arm Type

Active Comparator

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Intervention Type

Drug

Intervention Name(s)

tiotropium + olodaterol

Intervention Description

fixed dose combination

Intervention Type

Drug

Intervention Name(s)

tiotropium

Intervention Description

low dose

Intervention Type

Drug

Intervention Name(s)

olodaterol

Intervention Description

one dose only

Intervention Type

Drug

Intervention Name(s)

tiotropium

Intervention Description

high dose

Intervention Type

Drug

Intervention Name(s)

tiotropium + olodaterol

Intervention Description

fixed dose combination

Intervention Type

Device

Intervention Name(s)

Respimat

Intervention Description

Respimat inhaler

Primary Outcome Measure Information:

Title

Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.

Description

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.

Title

Trough FEV1 Response on Day 170.

Description

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

Title

Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 169

Secondary Outcome Measure Information:

Title

Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 169

Title

FEV1 AUC(0-3h) Response on Day 1

Description

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.

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.

Title

FEV1 AUC(0-3h) Response on Day 85

Description

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.

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.

Title

FEV1 AUC(0-3h) Response on Day 365

Description

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.

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.

Title

Trough FEV1 Response on Day 15.

Description

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

Title

Trough FEV1 Response on Day 43

Description

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.

Title

Trough FEV1 Response on Day 85

Description

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.

Title

Trough FEV1 Response on Day 169

Description

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

Title

Trough FEV1 Response on Day 365

Description

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

Title

FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1

Description

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.

Title

FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85

Description

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.

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.

Title

FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169

Description

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.

Title

FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365

Description

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.

Title

Trough FVC Response on Day 15.

Description

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

Title

Trough FVC Response on Day 43.

Description

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

Title

Trough FVC Response on Day 85.

Description

Time Frame

1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85

Title

Trough FVC Response on Day 170.

Description

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

Title

Trough FVC Response on Day 365.

Description

Time Frame

1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on Day 365.

Title

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)

Description

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.

Title

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)

Description

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.

Title

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)

Description

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.

Title

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)

Description

Time Frame

Title

Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 85

Title

Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 365

Title

Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 43

Title

Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 85

Title

Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

Description

Time Frame

Day 365

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Diagnosis of chronic obstructive pulmonary disease. Relatively stable airway obstruction with post FEV1< 80% predicted normal and post FEV1/FVC <70%. Male or female patients, 40 years of age or older. Smoking history of more than 10 pack years. Exclusion criteria: Significant disease other than COPD Clinically relevant abnormal lab values. History of asthma. Diagnosis of thyrotoxicosis Diagnosis of paroxysmal tachycardia History of myocardial infarction within 1 year of screening visit Unstable or life-threatening cardiac arrhythmia. Hospitalization for heart failure within the past year. Known active tuberculosis. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years History of life-threatening pulmonary obstruction. History of cystic fibrosis. Clinically evident bronchiectasis. History of significant alcohol or drug abuse. Thoracotomy with pulmonary resection Oral ß-adrenergics. Oral corticosteroid medication at unstable doses Regular use of daytime oxygen therapy for more than one hour per day Pulmonary rehabilitation program in the six weeks prior to the screening visit Investigational drug within one month or six half lives (whichever is greater) prior to screening visit Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA Pregnant or nursing women. Women of childbearing potential not using a highly effective method of birth control Patients who are unable to comply with pulmonary medication restrictions

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

1237.5.01038 Boehringer Ingelheim Investigational Site

City

Jasper

State/Province

Alabama

Country

United States

Facility Name

1237.5.01036 Boehringer Ingelheim Investigational Site

City

Mobile

State/Province

Alabama

Country

United States

Facility Name

1237.5.01015 Boehringer Ingelheim Investigational Site

City

Boulder

State/Province

Colorado

Country

United States

Facility Name

1237.5.01024 Boehringer Ingelheim Investigational Site

City

Wheat Ridge

State/Province

Colorado

Country

United States

Facility Name

1237.5.01034 Boehringer Ingelheim Investigational Site

City

Stamford

State/Province

Connecticut

Country

United States

Facility Name

1237.5.01003 Boehringer Ingelheim Investigational Site

City

Clearwater

State/Province

Florida

Country

United States

Facility Name

1237.5.01010 Boehringer Ingelheim Investigational Site

City

Clearwater

State/Province

Florida

Country

United States

Facility Name

1237.5.01027 Boehringer Ingelheim Investigational Site

City

Panama City

State/Province

Florida

Country

United States

Facility Name

1237.5.01031 Boehringer Ingelheim Investigational Site

City

O'Fallon

State/Province

Illinois

Country

United States

Facility Name

1237.5.01035 Boehringer Ingelheim Investigational Site

City

Opelousas

State/Province

Louisiana

Country

United States

Facility Name

1237.5.01004 Boehringer Ingelheim Investigational Site

City

Shreveport

State/Province

Louisiana

Country

United States

Facility Name

1237.5.01017 Boehringer Ingelheim Investigational Site

City

Biddeford

State/Province

Maine

Country

United States

Facility Name

1237.5.01028 Boehringer Ingelheim Investigational Site

City

Columbia

State/Province

Maryland

Country

United States

Facility Name

1237.5.01013 Boehringer Ingelheim Investigational Site

City

Livonia

State/Province

Michigan

Country

United States

Facility Name

1237.5.01019 Boehringer Ingelheim Investigational Site

City

Omaha

State/Province

Nebraska

Country

United States

Facility Name

1237.5.01025 Boehringer Ingelheim Investigational Site

City

Larchmont

State/Province

New York

Country

United States

Facility Name

1237.5.01008 Boehringer Ingelheim Investigational Site

City

Rochester

State/Province

New York

Country

United States

Facility Name

1237.5.01023 Boehringer Ingelheim Investigational Site

City

Raleigh

State/Province

North Carolina

Country

United States

Facility Name

1237.5.01016 Boehringer Ingelheim Investigational Site

City

Tabor City

State/Province

North Carolina

Country

United States

Facility Name

1237.5.01006 Boehringer Ingelheim Investigational Site

City

Cincinnati

State/Province

Ohio

Country

United States

Facility Name

1237.5.01040 Boehringer Ingelheim Investigational Site

City

Columbus

State/Province

Ohio

Country

United States

Facility Name

1237.5.01039 Boehringer Ingelheim Investigational Site

City

Dayton

State/Province

Ohio

Country

United States

Facility Name

1237.5.01037 Boehringer Ingelheim Investigational Site

City

Toledo

State/Province

Ohio

Country

United States

Facility Name

1237.5.01009 Boehringer Ingelheim Investigational Site

City

Oklahoma City

State/Province

Oklahoma

Country

United States

Facility Name

1237.5.01032 Boehringer Ingelheim Investigational Site

City

Charleston

State/Province

Pennsylvania

Country

United States

Facility Name

1237.5.01005 Boehringer Ingelheim Investigational Site

City

Johnston

State/Province

Rhode Island

Country

United States

Facility Name

1237.5.01021 Boehringer Ingelheim Investigational Site

City

Easley

State/Province

South Carolina

Country

United States

Facility Name

1237.5.01012 Boehringer Ingelheim Investigational Site

City

Gaffney

State/Province

South Carolina

Country

United States

Facility Name

1237.5.01014 Boehringer Ingelheim Investigational Site

City

Spartanburg

State/Province

South Carolina

Country

United States

Facility Name

1237.5.01029 Boehringer Ingelheim Investigational Site

City

Ft. Worth

State/Province

Texas

Country

United States

Facility Name

1237.5.01002 Boehringer Ingelheim Investigational Site

City

San Antonio

State/Province

Texas

Country

United States

Facility Name

1237.5.01026 Boehringer Ingelheim Investigational Site

City

Lynchburg

State/Province

Virginia

Country

United States

Facility Name

1237.5.01007 Boehringer Ingelheim Investigational Site

City

Spokane

State/Province

Washington

Country

United States

Facility Name

1237.5.01033 Boehringer Ingelheim Investigational Site

City

Tacoma

State/Province

Washington

Country

United States

Facility Name

1237.5.01001 Boehringer Ingelheim Investigational Site

City

Morgantown

State/Province

West Virginia

Country

United States

Facility Name

1237.5.54010 Boehringer Ingelheim Investigational Site

City

Buenos Aires

Country

Argentina

Facility Name

1237.5.54013 Boehringer Ingelheim Investigational Site

City

Caba

Country

Argentina

Facility Name

1237.5.54016 Boehringer Ingelheim Investigational Site

City

Caba

Country

Argentina

Facility Name

1237.5.54003 Boehringer Ingelheim Investigational Site

City

Capital Federal

Country

Argentina

Facility Name

1237.5.54002 Boehringer Ingelheim Investigational Site

City

Cuidad Autonoma de Buenos Airess A

Country

Argentina

Facility Name

1237.5.54006 Boehringer Ingelheim Investigational Site

City

Mar del Plata

Country

Argentina

Facility Name

1237.5.54007 Boehringer Ingelheim Investigational Site

City

Mar del Plata

Country

Argentina

Facility Name

1237.5.54009 Boehringer Ingelheim Investigational Site

City

Mendoza

Country

Argentina

Facility Name

1237.5.54012 Boehringer Ingelheim Investigational Site

City

Monte Grande

Country

Argentina

Facility Name

1237.5.54008 Boehringer Ingelheim Investigational Site

City

Quilmes

Country

Argentina

Facility Name

1237.5.54005 Boehringer Ingelheim Investigational Site

City

Rosario

Country

Argentina

Facility Name

1237.5.54011 Boehringer Ingelheim Investigational Site

City

San Miguel de Tucuman

Country

Argentina

Facility Name

1237.5.54004 Boehringer Ingelheim Investigational Site

City

San Miguel de Tucuma

Country

Argentina

Facility Name

1237.5.61001 Boehringer Ingelheim Investigational Site

City

Toorak Gardens

State/Province

South Australia

Country

Australia

Facility Name

1237.5.61002 Boehringer Ingelheim Investigational Site

City

Woodville

State/Province

South Australia

Country

Australia

Facility Name

1237.5.61004 Boehringer Ingelheim Investigational Site

City

Frankston

State/Province

Victoria

Country

Australia

Facility Name

1237.5.35905 Boehringer Ingelheim Investigational Site

City

Plovdiv

Country

Bulgaria

Facility Name

1237.5.35901 Boehringer Ingelheim Investigational Site

City

Rousse

Country

Bulgaria

Facility Name

1237.5.35906 Boehringer Ingelheim Investigational Site

City

Shumen

Country

Bulgaria

Facility Name

1237.5.35902 Boehringer Ingelheim Investigational Site

City

Sofia

Country

Bulgaria

Facility Name

1237.5.35904 Boehringer Ingelheim Investigational Site

City

Sofia

Country

Bulgaria

Facility Name

1237.5.35903 Boehringer Ingelheim Investigational Site

City

Troyan

Country

Bulgaria

Facility Name

1237.5.35908 Boehringer Ingelheim Investigational Site

City

Veliko Tarnovo

Country

Bulgaria

Facility Name

1237.5.02002 Boehringer Ingelheim Investigational Site

City

Calgary

State/Province

Alberta

Country

Canada

Facility Name

1237.5.02001 Boehringer Ingelheim Investigational Site

City

Vancouver

State/Province

British Columbia

Country

Canada

Facility Name

1237.5.02004 Boehringer Ingelheim Investigational Site

City

Winnipeg

State/Province

Manitoba

Country

Canada

Facility Name

1237.5.02005 Boehringer Ingelheim Investigational Site

City

Burlington

State/Province

Ontario

Country

Canada

Facility Name

1237.5.02007 Boehringer Ingelheim Investigational Site

City

Grimsby

State/Province

Ontario

Country

Canada

Facility Name

1237.5.02011 Boehringer Ingelheim Investigational Site

City

Ottawa

State/Province

Ontario

Country

Canada

Facility Name

1237.5.02008 Boehringer Ingelheim Investigational Site

City

Sherbrooke

State/Province

Quebec

Country

Canada

Facility Name

1237.5.02009 Boehringer Ingelheim Investigational Site

City

Saskatoon

State/Province

Saskatchewan

Country

Canada

Facility Name

1237.5.02003 Boehringer Ingelheim Investigational Site

City

Quebec

Country

Canada

Facility Name

1237.5.02006 Boehringer Ingelheim Investigational Site

City

Quebec

Country

Canada

Facility Name

1237.5.86003 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1237.5.86004 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1237.5.86011 Boehringer Ingelheim Investigational Site

City

Changsha

Country

China

Facility Name

1237.5.86012 Boehringer Ingelheim Investigational Site

City

Changsha

Country

China

Facility Name

1237.5.86014 Boehringer Ingelheim Investigational Site

City

Foshan

Country

China

Facility Name

1237.5.86001 Boehringer Ingelheim Investigational Site

City

Guangzhou

Country

China

Facility Name

1237.5.86015 Boehringer Ingelheim Investigational Site

City

Nan Ning

Country

China

Facility Name

1237.5.86002 Boehringer Ingelheim Investigational Site

City

Shanghai

Country

China

Facility Name

1237.5.86005 Boehringer Ingelheim Investigational Site

City

Shanghai

Country

China

Facility Name

1237.5.86006 Boehringer Ingelheim Investigational Site

City

Shanghai

Country

China

Facility Name

1237.5.86007 Boehringer Ingelheim Investigational Site

City

Shanghai

Country

China

Facility Name

1237.5.86009 Boehringer Ingelheim Investigational Site

City

Shenyang

Country

China

Facility Name

1237.5.86016 Boehringer Ingelheim Investigational Site

City

Wuhan

Country

China

Facility Name

1237.5.86010 Boehringer Ingelheim Investigational Site

City

Xi'An

Country

China

Facility Name

1237.5.86008 Boehringer Ingelheim Investigational Site

City

Yangzhou

Country

China

Facility Name

1237.5.86017 Boehringer Ingelheim Investigational Site

City

Yinchuan

Country

China

Facility Name

1237.5.42004 Boehringer Ingelheim Investigational Site

City

Beroun

Country

Czech Republic

Facility Name

1237.5.42002 Boehringer Ingelheim Investigational Site

City

Cvikov

Country

Czech Republic

Facility Name

1237.5.42001 Boehringer Ingelheim Investigational Site

City

Praha 6

Country

Czech Republic

Facility Name

1237.5.42005 Boehringer Ingelheim Investigational Site

City

Rokycany

Country

Czech Republic

Facility Name

1237.5.42003 Boehringer Ingelheim Investigational Site

City

Znojmo

Country

Czech Republic

Facility Name

1237.5.45002 Boehringer Ingelheim Investigational Site

City

Aalborg

Country

Denmark

Facility Name

1237.5.45009 Boehringer Ingelheim Investigational Site

City

Hvidovre

Country

Denmark

Facility Name

1237.5.45007 Boehringer Ingelheim Investigational Site

City

Kolding

Country

Denmark

Facility Name

1237.5.45001 Boehringer Ingelheim Investigational Site

City

København NV

Country

Denmark

Facility Name

1237.5.45011 Boehringer Ingelheim Investigational Site

City

Næstved

Country

Denmark

Facility Name

1237.5.45006 Boehringer Ingelheim Investigational Site

City

Odense C

Country

Denmark

Facility Name

1237.5.45008 Boehringer Ingelheim Investigational Site

City

Roskilde

Country

Denmark

Facility Name

1237.5.45003 Boehringer Ingelheim Investigational Site

City

Silkeborg

Country

Denmark

Facility Name

1237.5.45005 Boehringer Ingelheim Investigational Site

City

Sønderborg

Country

Denmark

Facility Name

1237.5.45004 Boehringer Ingelheim Investigational Site

City

Vaerløse

Country

Denmark

Facility Name

1237.5.37002 Boehringer Ingelheim Investigational Site

City

Tallin

Country

Estonia

Facility Name

1237.5.37001 Boehringer Ingelheim Investigational Site

City

Tartu

Country

Estonia

Facility Name

1237.5.35801 Boehringer Ingelheim Investigational Site

City

Helsinki

Country

Finland

Facility Name

1237.5.35804 Boehringer Ingelheim Investigational Site

City

Pori

Country

Finland

Facility Name

1237.5.35802 Boehringer Ingelheim Investigational Site

City

Turku

Country

Finland

Facility Name

1237.5.33004 Boehringer Ingelheim Investigational Site

City

Bethune Cedex

Country

France

Facility Name

1237.5.33007 Boehringer Ingelheim Investigational Site

City

Montpellier cedex 5

Country

France

Facility Name

1237.5.33005 Boehringer Ingelheim Investigational Site

City

Nantes

Country

France

Facility Name

1237.5.33006 Boehringer Ingelheim Investigational Site

City

Nîmes cedex 9

Country

France

Facility Name

1237.5.33008 Boehringer Ingelheim Investigational Site

City

Perpignan

Country

France

Facility Name

1237.5.33001 Boehringer Ingelheim Investigational Site

City

Saint Pierre Cedex

Country

France

Facility Name

1237.5.33002 Boehringer Ingelheim Investigational Site

City

Strasbourg

Country

France

Facility Name

1237.5.49006 Boehringer Ingelheim Investigational Site

City

Bamberg

Country

Germany

Facility Name

1237.5.49002 Boehringer Ingelheim Investigational Site

City

Berlin

Country

Germany

Facility Name

1237.5.49003 Boehringer Ingelheim Investigational Site

City

Berlin

Country

Germany

Facility Name

1237.5.49013 Boehringer Ingelheim Investigational Site

City

Berlin

Country

Germany

Facility Name

1237.5.49011 Boehringer Ingelheim Investigational Site

City

Erfurt

Country

Germany

Facility Name

1237.5.49005 Boehringer Ingelheim Investigational Site

City

Hamburg

Country

Germany

Facility Name

1237.5.49010 Boehringer Ingelheim Investigational Site

City

Hamburg

Country

Germany

Facility Name

1237.5.49009 Boehringer Ingelheim Investigational Site

City

Koblenz

Country

Germany

Facility Name

1237.5.49014 Boehringer Ingelheim Investigational Site

City

Neu-Isenburg

Country

Germany

Facility Name

1237.5.49012 Boehringer Ingelheim Investigational Site

City

Oschersleben

Country

Germany

Facility Name

1237.5.49001 Boehringer Ingelheim Investigational Site

City

Rüdersdorf

Country

Germany

Facility Name

1237.5.49004 Boehringer Ingelheim Investigational Site

City

Weinheim

Country

Germany

Facility Name

1237.5.49008 Boehringer Ingelheim Investigational Site

City

Wiesloch

Country

Germany

Facility Name

1237.5.50201 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.50202 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.50203 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.50204 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.50205 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.50206 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.50207 Boehringer Ingelheim Investigational Site

City

Guatemala

Country

Guatemala

Facility Name

1237.5.36005 Boehringer Ingelheim Investigational Site

City

Debrecen

Country

Hungary

Facility Name

1237.5.36001 Boehringer Ingelheim Investigational Site

City

Deszk

Country

Hungary

Facility Name

1237.5.36006 Boehringer Ingelheim Investigational Site

City

Kapuvar

Country

Hungary

Facility Name

1237.5.36003 Boehringer Ingelheim Investigational Site

City

Szombathely

Country

Hungary

Facility Name

1237.5.36002 Boehringer Ingelheim Investigational Site

City

Törökbalint

Country

Hungary

Facility Name

1237.5.91010 Boehringer Ingelheim Investigational Site

City

Ahmedabad

Country

India

Facility Name

1237.5.91002 Boehringer Ingelheim Investigational Site

City

Bangalore

Country

India

Facility Name

1237.5.91007 Boehringer Ingelheim Investigational Site

City

Bangalore

Country

India

Facility Name

1237.5.91004 Boehringer Ingelheim Investigational Site

City

Coimbatore

Country

India

Facility Name

1237.5.91011 Boehringer Ingelheim Investigational Site

City

Hyderabad

Country

India

Facility Name

1237.5.91001 Boehringer Ingelheim Investigational Site

City

Jaipur

Country

India

Facility Name

1237.5.91008 Boehringer Ingelheim Investigational Site

City

Jaipur

Country

India

Facility Name

1237.5.91009 Boehringer Ingelheim Investigational Site

City

Mysore

Country

India

Facility Name

1237.5.91006 Boehringer Ingelheim Investigational Site

City

Pune

Country

India

Facility Name

1237.5.39008 Boehringer Ingelheim Investigational Site

City

Cagliari

Country

Italy

Facility Name

1237.5.39002 Boehringer Ingelheim Investigational Site

City

Genova

Country

Italy

Facility Name

1237.5.39006 Boehringer Ingelheim Investigational Site

City

Montescano (PV)

Country

Italy

Facility Name

1237.5.39009 Boehringer Ingelheim Investigational Site

City

Monza

Country

Italy

Facility Name

1237.5.39004 Boehringer Ingelheim Investigational Site

City

Parma

Country

Italy

Facility Name

1237.5.39001 Boehringer Ingelheim Investigational Site

City

Pisa

Country

Italy

Facility Name

1237.5.81003 Boehringer Ingelheim Investigational Site

City

Aoba-ku, Sendai, Miyagi

Country

Japan

Facility Name

1237.5.81001 Boehringer Ingelheim Investigational Site

City

Asahikawa, Hokkaido

Country

Japan

Facility Name

1237.5.81006 Boehringer Ingelheim Investigational Site

City

Bunkyo-ku, Tokyo

Country

Japan

Facility Name

1237.5.81044 Boehringer Ingelheim Investigational Site

City

Chuo-ku, Kumamoto, Kumamoto

Country

Japan

Facility Name

1237.5.81035 Boehringer Ingelheim Investigational Site

City

Gifu, Gifu

Country

Japan

Facility Name

1237.5.81017 Boehringer Ingelheim Investigational Site

City

Hakata-ku, Fukuoka, Fukuoka

Country

Japan

Facility Name

1237.5.81031 Boehringer Ingelheim Investigational Site

City

Hamamatsushi, Shizuoka

Country

Japan

Facility Name

1237.5.81014 Boehringer Ingelheim Investigational Site

City

Himeji, Hyogo

Country

Japan

Facility Name

1237.5.81037 Boehringer Ingelheim Investigational Site

City

Ikoma, Nara

Country

Japan

Facility Name

1237.5.81024 Boehringer Ingelheim Investigational Site

City

Inashiki-gun, Ibaraki

Country

Japan

Facility Name

1237.5.81008 Boehringer Ingelheim Investigational Site

City

Itabashi-ku, Tokyo

Country

Japan

Facility Name

1237.5.81016 Boehringer Ingelheim Investigational Site

City

Jonan-ku, Fukuoka, Fukuoka

Country

Japan

Facility Name

1237.5.81020 Boehringer Ingelheim Investigational Site

City

Kagoshima, Kagoshima,

Country

Japan

Facility Name

1237.5.81021 Boehringer Ingelheim Investigational Site

City

Kagoshima, Kagoshima

Country

Japan

Facility Name

1237.5.81005 Boehringer Ingelheim Investigational Site

City

Kamogawa, Chiba

Country

Japan

Facility Name

1237.5.81011 Boehringer Ingelheim Investigational Site

City

Kishiwada, Osaka

Country

Japan

Facility Name

1237.5.81018 Boehringer Ingelheim Investigational Site

City

Kitakyusyu,Fukuoka

Country

Japan

Facility Name

1237.5.81042 Boehringer Ingelheim Investigational Site

City

Koga, Fukuoka

Country

Japan

Facility Name

1237.5.81032 Boehringer Ingelheim Investigational Site

City

Komaki, Aichi

Country

Japan

Facility Name

1237.5.81033 Boehringer Ingelheim Investigational Site

City

Komaki, Aichi

Country

Japan

Facility Name

1237.5.81019 Boehringer Ingelheim Investigational Site

City

Koshi, Kumamoto

Country

Japan

Facility Name

1237.5.81027 Boehringer Ingelheim Investigational Site

City

koto-ku, Tokyo

Country

Japan

Facility Name

1237.5.81025 Boehringer Ingelheim Investigational Site

City

Kuki, Saitama

Country

Japan

Facility Name

1237.5.81038 Boehringer Ingelheim Investigational Site

City

Kure, Hiroshima

Country

Japan

Facility Name

1237.5.81015 Boehringer Ingelheim Investigational Site

City

Kurume, Fukuoka

Country

Japan

Facility Name

1237.5.81029 Boehringer Ingelheim Investigational Site

City

Matsumoto, Nagano

Country

Japan

Facility Name

1237.5.81030 Boehringer Ingelheim Investigational Site

City

Matsumoto, Nagano

Country

Japan

Facility Name

1237.5.81010 Boehringer Ingelheim Investigational Site

City

Matsusaka, Mie

Country

Japan

Facility Name

1237.5.81041 Boehringer Ingelheim Investigational Site

City

Minami-ku. Fukuoka, Fukuoka

Country

Japan

Facility Name

1237.5.81002 Boehringer Ingelheim Investigational Site

City

Morioka, Iwate

Country

Japan

Facility Name

1237.5.81034 Boehringer Ingelheim Investigational Site

City

Nagoya, Aichi

Country

Japan

Facility Name

1237.5.81036 Boehringer Ingelheim Investigational Site

City

Nagoya, Aichi

Country

Japan

Facility Name

1237.5.81004 Boehringer Ingelheim Investigational Site

City

Naka-gun, Ibaraki

Country

Japan

Facility Name

1237.5.81022 Boehringer Ingelheim Investigational Site

City

Okinawa, Urasoe

Country

Japan

Facility Name

1237.5.81023 Boehringer Ingelheim Investigational Site

City

Okinawa, Urasoe

Country

Japan

Facility Name

1237.5.81012 Boehringer Ingelheim Investigational Site

City

Sayama, Osaka

Country

Japan

Facility Name

1237.5.81045 Boehringer Ingelheim Investigational Site

City

Sendai, Miyagi

Country

Japan

Facility Name

1237.5.81009 Boehringer Ingelheim Investigational Site

City

Seto, Aichi

Country

Japan

Facility Name

1237.5.81026 Boehringer Ingelheim Investigational Site

City

Shinagawa, Tokyo

Country

Japan

Facility Name

1237.5.81007 Boehringer Ingelheim Investigational Site

City

Shinjyuku-ku, Tokyo

Country

Japan

Facility Name

1237.5.81039 Boehringer Ingelheim Investigational Site

City

Takamatsu, Kagawa

Country

Japan

Facility Name

1237.5.81040 Boehringer Ingelheim Investigational Site

City

Takamatsu, Kagawa

Country

Japan

Facility Name

1237.5.81013 Boehringer Ingelheim Investigational Site

City

Wakayama, Wakayama

Country

Japan

Facility Name

1237.5.81043 Boehringer Ingelheim Investigational Site

City

Yanagawa-shi, Fukuoka,

Country

Japan

Facility Name

1237.5.81028 Boehringer Ingelheim Investigational Site

City

Yokohama, Kanagawa

Country

Japan

Facility Name

1237.5.82004 Boehringer Ingelheim Investigational Site

City

Bucheon

Country

Korea, Republic of

Facility Name

1237.5.82008 Boehringer Ingelheim Investigational Site

City

Daegu

Country

Korea, Republic of

Facility Name

1237.5.82001 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1237.5.82002 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1237.5.82003 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1237.5.82007 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1237.5.82005 Boehringer Ingelheim Investigational Site

City

Suwon

Country

Korea, Republic of

Facility Name

1237.5.82006 Boehringer Ingelheim Investigational Site

City

Wonju

Country

Korea, Republic of

Facility Name

1237.5.52002 Boehringer Ingelheim Investigational Site

City

Hermosillo

Country

Mexico

Facility Name

1237.5.52003 Boehringer Ingelheim Investigational Site

City

Mexico

Country

Mexico

Facility Name

1237.5.52007 Boehringer Ingelheim Investigational Site

City

Monterrey

Country

Mexico

Facility Name

1237.5.52001 Boehringer Ingelheim Investigational Site

City

Tijuana

Country

Mexico

Facility Name

1237.5.31004 Boehringer Ingelheim Investigational Site

City

Almelo

Country

Netherlands

Facility Name

1237.5.31006 Boehringer Ingelheim Investigational Site

City

Breda

Country

Netherlands

Facility Name

1237.5.31001 Boehringer Ingelheim Investigational Site

City

Eindhoven

Country

Netherlands

Facility Name

1237.5.31008 Boehringer Ingelheim Investigational Site

City

Harderwijk

Country

Netherlands

Facility Name

1237.5.31007 Boehringer Ingelheim Investigational Site

City

Heerlen

Country

Netherlands

Facility Name

1237.5.31010 Boehringer Ingelheim Investigational Site

City

Hengelo

Country

Netherlands

Facility Name

1237.5.31009 Boehringer Ingelheim Investigational Site

City

Hoorn

Country

Netherlands

Facility Name

1237.5.31005 Boehringer Ingelheim Investigational Site

City

Nieuwegein

Country

Netherlands

Facility Name

1237.5.31002 Boehringer Ingelheim Investigational Site

City

Veldhoven

Country

Netherlands

Facility Name

1237.5.31003 Boehringer Ingelheim Investigational Site

City

Zutphen

Country

Netherlands

Facility Name

1237.5.64002 Boehringer Ingelheim Investigational Site

City

Dunedin

Country

New Zealand

Facility Name

1237.5.64001 Boehringer Ingelheim Investigational Site

City

Greenlane East Auckland NZ

Country

New Zealand

Facility Name

1237.5.35105 Boehringer Ingelheim Investigational Site

City

Amadora

Country

Portugal

Facility Name

1237.5.35101 Boehringer Ingelheim Investigational Site

City

Coimbra

Country

Portugal

Facility Name

1237.5.35102 Boehringer Ingelheim Investigational Site

City

Lisboa

Country

Portugal

Facility Name

1237.5.35104 Boehringer Ingelheim Investigational Site

City

Lisboa

Country

Portugal

Facility Name

1237.5.35103 Boehringer Ingelheim Investigational Site

City

Porto

Country

Portugal

Facility Name

1237.5.35106 Boehringer Ingelheim Investigational Site

City

Vila Nova de Gaia

Country

Portugal

Facility Name

1237.5.35107 Boehringer Ingelheim Investigational Site

City

Viseu

Country

Portugal

Facility Name

1237.5.07001 Boehringer Ingelheim Investigational Site

City

Gatchina (Leningradskaya oblast)

Country

Russian Federation

Facility Name

1237.5.07003 Boehringer Ingelheim Investigational Site

City

Kazan

Country

Russian Federation

Facility Name

1237.5.07004 Boehringer Ingelheim Investigational Site

City

Moscow

Country

Russian Federation

Facility Name

1237.5.07005 Boehringer Ingelheim Investigational Site

City

Moscow

Country

Russian Federation

Facility Name

1237.5.07002 Boehringer Ingelheim Investigational Site

City

St. Petersburg

Country

Russian Federation

Facility Name

1237.5.38601 Boehringer Ingelheim Investigational Site

City

Golnik

Country

Slovenia

Facility Name

1237.5.38602 Boehringer Ingelheim Investigational Site

City

Golnik

Country

Slovenia

Facility Name

1237.5.90003 Boehringer Ingelheim Investigational Site

City

Istanbul

Country

Turkey

Facility Name

1237.5.90004 Boehringer Ingelheim Investigational Site

City

Istanbul

Country

Turkey

Facility Name

1237.5.90002 Boehringer Ingelheim Investigational Site

City

Izmir

Country

Turkey

Facility Name

1237.5.90005 Boehringer Ingelheim Investigational Site

City

Izmit

Country

Turkey

Facility Name

1237.5.90001 Boehringer Ingelheim Investigational Site

City

Mersin

Country

Turkey

12. IPD Sharing Statement

Citations:

PubMed Identifier

33175291

Citation

Rabe KF, Chalmers JD, Miravitlles M, Kocks JWH, Tsiligianni I, de la Hoz A, Xue W, Singh D, Ferguson GT, Wedzicha J. Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO(R) Trials. Adv Ther. 2021 Jan;38(1):579-593. doi: 10.1007/s12325-020-01528-2. Epub 2020 Nov 11.

Results Reference

derived

PubMed Identifier

32943047

Citation

Singh D, Wedzicha JA, Siddiqui S, de la Hoz A, Xue W, Magnussen H, Miravitlles M, Chalmers JD, Calverley PMA. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.

Results Reference

derived

PubMed Identifier

32848380

Citation

Andreas S, Bothner U, de la Hoz A, Kloer I, Trampisch M, Alter P. No Influence on Cardiac Arrhythmia or Heart Rate from Long-Term Treatment with Tiotropium/Olodaterol versus Monocomponents by Holter ECG Analysis in Patients with Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1945-1953. doi: 10.2147/COPD.S246350. eCollection 2020.

Results Reference

derived

PubMed Identifier

32848379

Citation

Andreas S, McGarvey L, Bothner U, Trampisch M, de la Hoz A, Flezar M, Buhl R, Alter P. Absence of Adverse Effects of Tiotropium/Olodaterol Compared with the Monocomponents on Long-Term Heart Rate and Blood Pressure in Patients with Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1935-1944. doi: 10.2147/COPD.S246348. eCollection 2020.

Results Reference

derived

PubMed Identifier

32776202

Citation

Wedzicha JA, Buhl R, Singh D, Vogelmeier CF, de la Hoz A, Xue W, Anzueto A, Calverley PMA. Tiotropium/Olodaterol Decreases Exacerbation Rates Compared with Tiotropium in a Range of Patients with COPD: Pooled Analysis of the TONADO(R)/DYNAGITO(R) Trials. Adv Ther. 2020 Oct;37(10):4266-4279. doi: 10.1007/s12325-020-01438-3. Epub 2020 Aug 10.

Results Reference

derived

PubMed Identifier

32671684

Citation

Buhl R, de la Hoz A, Xue W, Singh D, Ferguson GT. Efficacy of Tiotropium/Olodaterol Compared with Tiotropium as a First-Line Maintenance Treatment in Patients with COPD Who Are Naive to LAMA, LABA and ICS: Pooled Analysis of Four Clinical Trials. Adv Ther. 2020 Oct;37(10):4175-4189. doi: 10.1007/s12325-020-01411-0. Epub 2020 Jul 15.

Results Reference

derived

PubMed Identifier

32462607

Citation

Buhl R, Singh D, de la Hoz A, Xue W, Ferguson GT. Benefits of Tiotropium/Olodaterol Compared with Tiotropium in Patients with COPD Receiving only LAMA at Baseline: Pooled Analysis of the TONADO(R) and OTEMTO(R) Studies. Adv Ther. 2020 Aug;37(8):3485-3499. doi: 10.1007/s12325-020-01373-3. Epub 2020 May 27.

Results Reference

derived

PubMed Identifier

30261995

Citation

Ferguson GT, Buhl R, Bothner U, Hoz A, Voss F, Anzueto A, Calverley PMA. Safety of tiotropium/olodaterol in chronic obstructive pulmonary disease: pooled analysis of three large, 52-week, randomized clinical trials. Respir Med. 2018 Oct;143:67-73. doi: 10.1016/j.rmed.2018.08.012. Epub 2018 Aug 28.

Results Reference

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PubMed Identifier

29355547

Citation

Maltais F, Buhl R, Koch A, Amatto VC, Reid J, Gronke L, Bothner U, Voss F, McGarvey L, Ferguson GT. beta-Blockers in COPD: A Cohort Study From the TONADO Research Program. Chest. 2018 Jun;153(6):1315-1325. doi: 10.1016/j.chest.2018.01.008. Epub 2018 Jan 31.

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PubMed Identifier

27993292

Citation

Buhl R, Magder S, Bothner U, Tetzlaff K, Voss F, Loaiza L, Vogelmeier CF, McGarvey L. Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease. Respir Med. 2017 Jan;122:58-66. doi: 10.1016/j.rmed.2016.11.011. Epub 2016 Nov 14.

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PubMed Identifier

26112656

Citation

Ferguson GT, Flezar M, Korn S, Korducki L, Gronke L, Abrahams R, Buhl R. Efficacy of Tiotropium + Olodaterol in Patients with Chronic Obstructive Pulmonary Disease by Initial Disease Severity and Treatment Intensity: A Post Hoc Analysis. Adv Ther. 2015 Jun;32(6):523-36. doi: 10.1007/s12325-015-0218-0. Epub 2015 Jun 26.

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derived

PubMed Identifier

25573406

Citation

Buhl R, Maltais F, Abrahams R, Bjermer L, Derom E, Ferguson G, Flezar M, Hebert J, McGarvey L, Pizzichini E, Reid J, Veale A, Gronke L, Hamilton A, Korducki L, Tetzlaff K, Waitere-Wijker S, Watz H, Bateman E. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4). Eur Respir J. 2015 Apr;45(4):969-79. doi: 10.1183/09031936.00136014. Epub 2015 Jan 8. Erratum In: Eur Respir J. 2015 Jun;45(6):1763.

Results Reference

derived

Links:

URL

http://trials.boehringer-ingelheim.com/

Description

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Learn more about this trial

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

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

Pulmonary Disease, Chronic Obstructive

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial