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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

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 high dose FDC

tiotropium+olodaterol low 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 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

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

Secondary Outcome Measures

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

Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) is the key secondary endpoint. The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

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

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

Forced Vital Capacity (FVC) 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.

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

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

FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.

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

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

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 Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.

FEV1 AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.

FVC AUC(0-12h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.

FVC AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.

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

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

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

Mahler TDI focal score on Day 43 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

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

Mahler TDI focal score on Day 85 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

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

Mahler TDI focal score on Day 365 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

Full Information

NCT ID

NCT01431287

First Posted

September 8, 2011

Last Updated

June 19, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01431287

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 2]

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

September 2011 (undefined)

Primary Completion Date

November 2013 (Actual)

Study Completion Date

November 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 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

2539 (Actual)

8. Arms, Groups, and Interventions

Arm Title

tiotropium+olodaterol high dose FDC

Arm Type

Experimental

Arm Description

Once daily 2 puffs solution for inhalation Respimat

Arm Title

tiotropium+olodaterol low 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 + olodaterol

Intervention Description

fixed dose combination

Intervention Type

Drug

Intervention Name(s)

tiotropium

Intervention Description

low dose or high dose

Intervention Type

Drug

Intervention Name(s)

tiotropium

Intervention Description

low dose or high dose

Intervention Type

Drug

Intervention Name(s)

olodaterol

Intervention Description

one dose only

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 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

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 1hr 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 1hr 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

Forced Vital Capacity (FVC) 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

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

Description

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

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

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 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169

Title

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

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 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 23h and at 23h 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 Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

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 Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

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 Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

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 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

Description

Time Frame

Title

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

Description

Time Frame

Day 85

Title

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

Description

Time Frame

Day 365

Title

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

Description

Time Frame

Day 43

Title

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

Description

Time Frame

Day 85

Title

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

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

1237.6.01106 Boehringer Ingelheim Investigational Site

City

Greer

State/Province

California

Country

United States

Facility Name

1237.6.01120 Boehringer Ingelheim Investigational Site

City

Fort Collins

State/Province

Colorado

Country

United States

Facility Name

1237.6.01131 Boehringer Ingelheim Investigational Site

City

Danbury

State/Province

Connecticut

Country

United States

Facility Name

1237.6.01117 Boehringer Ingelheim Investigational Site

City

Waterbury

State/Province

Connecticut

Country

United States

Facility Name

1237.6.01118 Boehringer Ingelheim Investigational Site

City

Deland

State/Province

Florida

Country

United States

Facility Name

1237.6.01126 Boehringer Ingelheim Investigational Site

City

Tampa

State/Province

Florida

Country

United States

Facility Name

1237.6.01109 Boehringer Ingelheim Investigational Site

City

Winter Park

State/Province

Florida

Country

United States

Facility Name

1237.6.01134 Boehringer Ingelheim Investigational Site

City

Atlanta

State/Province

Georgia

Country

United States

Facility Name

1237.6.01107 Boehringer Ingelheim Investigational Site

City

Couer d'Alene

State/Province

Idaho

Country

United States

Facility Name

1237.6.01110 Boehringer Ingelheim Investigational Site

City

Lafayette

State/Province

Louisiana

Country

United States

Facility Name

1237.6.01128 Boehringer Ingelheim Investigational Site

City

Baltimore

State/Province

Maryland

Country

United States

Facility Name

1237.6.01130 Boehringer Ingelheim Investigational Site

City

North Dartmouth

State/Province

Massachusetts

Country

United States

Facility Name

1237.6.01104 Boehringer Ingelheim Investigational Site

City

Minneapolis

State/Province

Minnesota

Country

United States

Facility Name

1237.6.01116 Boehringer Ingelheim Investigational Site

City

Plymouth

State/Province

Minnesota

Country

United States

Facility Name

1237.6.01121 Boehringer Ingelheim Investigational Site

City

St. Louis

State/Province

Missouri

Country

United States

Facility Name

1237.6.01123 Boehringer Ingelheim Investigational Site

City

St. Louis

State/Province

Missouri

Country

United States

Facility Name

1237.6.01129 Boehringer Ingelheim Investigational Site

City

Henderson

State/Province

Nevada

Country

United States

Facility Name

1237.6.01136 Boehringer Ingelheim Investigational Site

City

Marlton

State/Province

New Jersey

Country

United States

Facility Name

1237.6.01108 Boehringer Ingelheim Investigational Site

City

Albuquerque

State/Province

New Mexico

Country

United States

Facility Name

1237.6.01127 Boehringer Ingelheim Investigational Site

City

Bayside

State/Province

New York

Country

United States

Facility Name

1237.6.01139 Boehringer Ingelheim Investigational Site

City

Great Neck

State/Province

New York

Country

United States

Facility Name

1237.6.01135 Boehringer Ingelheim Investigational Site

City

Charlotte

State/Province

North Carolina

Country

United States

Facility Name

1237.6.01114 Boehringer Ingelheim Investigational Site

City

Cincinnati

State/Province

Ohio

Country

United States

Facility Name

1237.6.01102 Boehringer Ingelheim Investigational Site

City

Columbus

State/Province

Ohio

Country

United States

Facility Name

1237.6.01115 Boehringer Ingelheim Investigational Site

City

Oklahoma City

State/Province

Oklahoma

Country

United States

Facility Name

1237.6.01101 Boehringer Ingelheim Investigational Site

City

Philadelphia

State/Province

Pennsylvania

Country

United States

Facility Name

1237.6.01113 Boehringer Ingelheim Investigational Site

City

East Providence

State/Province

Rhode Island

Country

United States

Facility Name

1237.6.01122 Boehringer Ingelheim Investigational Site

City

Charleston

State/Province

South Carolina

Country

United States

Facility Name

1237.6.01132 Boehringer Ingelheim Investigational Site

City

Greenville

State/Province

South Carolina

Country

United States

Facility Name

1237.6.01137 Boehringer Ingelheim Investigational Site

City

Greenville

State/Province

South Carolina

Country

United States

Facility Name

1237.6.01111 Boehringer Ingelheim Investigational Site

City

Spartanburg

State/Province

South Carolina

Country

United States

Facility Name

1237.6.01105 Boehringer Ingelheim Investigational Site

City

Union

State/Province

South Carolina

Country

United States

Facility Name

1237.6.01138 Boehringer Ingelheim Investigational Site

City

Killeen

State/Province

Texas

Country

United States

Facility Name

1237.6.01124 Boehringer Ingelheim Investigational Site

City

McKinney

State/Province

Texas

Country

United States

Facility Name

1237.6.01112 Boehringer Ingelheim Investigational Site

City

Richmond

State/Province

Virginia

Country

United States

Facility Name

1237.6.01133 Boehringer Ingelheim Investigational Site

City

Richmond

State/Province

Virginia

Country

United States

Facility Name

1237.6.01125 Boehringer Ingelheim Investigational Site

City

Spokane

State/Province

Washington

Country

United States

Facility Name

1237.6.01103 Boehringer Ingelheim Investigational Site

City

Tacoma

State/Province

Washington

Country

United States

Facility Name

1237.6.43006 Boehringer Ingelheim Investigational Site

City

Feldbach

Country

Austria

Facility Name

1237.6.43005 Boehringer Ingelheim Investigational Site

City

Gänserndorf

Country

Austria

Facility Name

1237.6.43002 Boehringer Ingelheim Investigational Site

City

Innsbruck

Country

Austria

Facility Name

1237.6.43004 Boehringer Ingelheim Investigational Site

City

Leoben

Country

Austria

Facility Name

1237.6.43001 Boehringer Ingelheim Investigational Site

City

Linz

Country

Austria

Facility Name

1237.6.43003 Boehringer Ingelheim Investigational Site

City

Salzburg

Country

Austria

Facility Name

1237.6.32007 Boehringer Ingelheim Investigational Site

City

Brussel

Country

Belgium

Facility Name

1237.6.32005 Boehringer Ingelheim Investigational Site

City

Bruxelles

Country

Belgium

Facility Name

1237.6.32004 Boehringer Ingelheim Investigational Site

City

Gent

Country

Belgium

Facility Name

1237.6.32002 Boehringer Ingelheim Investigational Site

City

Jambes

Country

Belgium

Facility Name

1237.6.32009 Boehringer Ingelheim Investigational Site

City

Lebbeke

Country

Belgium

Facility Name

1237.6.32001 Boehringer Ingelheim Investigational Site

City

Leuven

Country

Belgium

Facility Name

1237.6.32006 Boehringer Ingelheim Investigational Site

City

Liège

Country

Belgium

Facility Name

1237.6.32008 Boehringer Ingelheim Investigational Site

City

Oostende

Country

Belgium

Facility Name

1237.6.32010 Boehringer Ingelheim Investigational Site

City

Turnhout

Country

Belgium

Facility Name

1237.6.55013 Boehringer Ingelheim Investigational Site

City

Botucatu

Country

Brazil

Facility Name

1237.6.55010 Boehringer Ingelheim Investigational Site

City

Florianopolis

Country

Brazil

Facility Name

1237.6.55012 Boehringer Ingelheim Investigational Site

City

Passo Fundo

Country

Brazil

Facility Name

1237.6.55001 Boehringer Ingelheim Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

1237.6.55002 Boehringer Ingelheim Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

1237.6.55003 Boehringer Ingelheim Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

1237.6.55005 Boehringer Ingelheim Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

1237.6.55009 Boehringer Ingelheim Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

1237.6.55006 Boehringer Ingelheim Investigational Site

City

Sao Paulo

Country

Brazil

Facility Name

1237.6.55007 Boehringer Ingelheim Investigational Site

City

Sao Paulo

Country

Brazil

Facility Name

1237.6.55011 Boehringer Ingelheim Investigational Site

City

Sao Paulo

Country

Brazil

Facility Name

1237.6.02109 Boehringer Ingelheim Investigational Site

City

Edmonton

State/Province

Alberta

Country

Canada

Facility Name

1237.6.02111 Boehringer Ingelheim Investigational Site

City

Vancouver

State/Province

British Columbia

Country

Canada

Facility Name

1237.6.02106 Boehringer Ingelheim Investigational Site

City

Moncton

State/Province

New Brunswick

Country

Canada

Facility Name

1237.6.02110 Boehringer Ingelheim Investigational Site

City

Courtice

State/Province

Ontario

Country

Canada

Facility Name

1237.6.02101 Boehringer Ingelheim Investigational Site

City

Downsview

State/Province

Ontario

Country

Canada

Facility Name

1237.6.02112 Boehringer Ingelheim Investigational Site

City

Sarnia

State/Province

Ontario

Country

Canada

Facility Name

1237.6.02103 Boehringer Ingelheim Investigational Site

City

Toronto

State/Province

Ontario

Country

Canada

Facility Name

1237.6.02102 Boehringer Ingelheim Investigational Site

City

Windsor

State/Province

Ontario

Country

Canada

Facility Name

1237.6.02104 Boehringer Ingelheim Investigational Site

City

Point Claire

State/Province

Quebec

Country

Canada

Facility Name

1237.6.02105 Boehringer Ingelheim Investigational Site

City

Sherbrooke

State/Province

Quebec

Country

Canada

Facility Name

1237.6.02108 Boehringer Ingelheim Investigational Site

City

Ste-Foy

State/Province

Quebec

Country

Canada

Facility Name

1237.6.86117 Boehringer Ingelheim Investigational Site

City

Baotou

Country

China

Facility Name

1237.6.86102 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1237.6.86104 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1237.6.86105 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1237.6.86115 Boehringer Ingelheim Investigational Site

City

Changsha

Country

China

Facility Name

1237.6.86110 Boehringer Ingelheim Investigational Site

City

Chengdu

Country

China

Facility Name

1237.6.86111 Boehringer Ingelheim Investigational Site

City

Chongqing

Country

China

Facility Name

1237.6.86109 Boehringer Ingelheim Investigational Site

City

Haikou

Country

China

Facility Name

1237.6.86108 Boehringer Ingelheim Investigational Site

City

Hangzhou

Country

China

Facility Name

1237.6.86116 Boehringer Ingelheim Investigational Site

City

Hohhot

Country

China

Facility Name

1237.6.86114 Boehringer Ingelheim Investigational Site

City

Jinan

Country

China

Facility Name

1237.6.86106 Boehringer Ingelheim Investigational Site

City

Nanjing

Country

China

Facility Name

1237.6.86101 Boehringer Ingelheim Investigational Site

City

Shanghai

Country

China

Facility Name

1237.6.86113 Boehringer Ingelheim Investigational Site

City

Shenyang

Country

China

Facility Name

1237.6.86107 Boehringer Ingelheim Investigational Site

City

Suzhou

Country

China

Facility Name

1237.6.86112 Boehringer Ingelheim Investigational Site

City

Xi'An

Country

China

Facility Name

1237.6.57001 Boehringer Ingelheim Investigational Site

City

Bogota DC

Country

Colombia

Facility Name

1237.6.57003 Boehringer Ingelheim Investigational Site

City

Bogota DC

Country

Colombia

Facility Name

1237.6.57007 Boehringer Ingelheim Investigational Site

City

Bogota DC

Country

Colombia

Facility Name

1237.6.57008 Boehringer Ingelheim Investigational Site

City

Bogota

Country

Colombia

Facility Name

1237.6.57006 Boehringer Ingelheim Investigational Site

City

Cali

Country

Colombia

Facility Name

1237.6.57004 Boehringer Ingelheim Investigational Site

City

Floridablanca

Country

Colombia

Facility Name

1237.6.38503 Boehringer Ingelheim Investigational Site

City

Petrinja

Country

Croatia

Facility Name

1237.6.38504 Boehringer Ingelheim Investigational Site

City

Rijeka

Country

Croatia

Facility Name

1237.6.38502 Boehringer Ingelheim Investigational Site

City

Zadar

Country

Croatia

Facility Name

1237.6.38501 Boehringer Ingelheim Investigational Site

City

Zagreb

Country

Croatia

Facility Name

1237.6.49022 Boehringer Ingelheim Investigational Site

City

Aschaffenburg

Country

Germany

Facility Name

1237.6.49017 Boehringer Ingelheim Investigational Site

City

Berlin

Country

Germany

Facility Name

1237.6.49026 Boehringer Ingelheim Investigational Site

City

Frankfurt

Country

Germany

Facility Name

1237.6.49027 Boehringer Ingelheim Investigational Site

City

Frankfurt

Country

Germany

Facility Name

1237.6.49025 Boehringer Ingelheim Investigational Site

City

Großhansdorf

Country

Germany

Facility Name

1237.6.49016 Boehringer Ingelheim Investigational Site

City

Halle

Country

Germany

Facility Name

1237.6.49024 Boehringer Ingelheim Investigational Site

City

Hamburg

Country

Germany

Facility Name

1237.6.49021 Boehringer Ingelheim Investigational Site

City

Hannover

Country

Germany

Facility Name

1237.6.49019 Boehringer Ingelheim Investigational Site

City

Leipzig

Country

Germany

Facility Name

1237.6.49028 Boehringer Ingelheim Investigational Site

City

Mainz

Country

Germany

Facility Name

1237.6.49018 Boehringer Ingelheim Investigational Site

City

Rodgau/Dudenhofen

Country

Germany

Facility Name

1237.6.49020 Boehringer Ingelheim Investigational Site

City

Schwerin

Country

Germany

Facility Name

1237.6.49023 Boehringer Ingelheim Investigational Site

City

Teuchern

Country

Germany

Facility Name

1237.6.36001 Boehringer Ingelheim Investigational Site

City

Debrecen

Country

Hungary

Facility Name

1237.6.36004 Boehringer Ingelheim Investigational Site

City

Gödöllö

Country

Hungary

Facility Name

1237.6.36005 Boehringer Ingelheim Investigational Site

City

Pecs

Country

Hungary

Facility Name

1237.6.36003 Boehringer Ingelheim Investigational Site

City

Sopron

Country

Hungary

Facility Name

1237.6.36002 Boehringer Ingelheim Investigational Site

City

Szeged

Country

Hungary

Facility Name

1237.6.91003 Boehringer Ingelheim Investigational Site

City

Chennai

Country

India

Facility Name

1237.6.91011 Boehringer Ingelheim Investigational Site

City

Coimbatore

Country

India

Facility Name

1237.6.91004 Boehringer Ingelheim Investigational Site

City

Jaipur

Country

India

Facility Name

1237.6.91002 Boehringer Ingelheim Investigational Site

City

Kolkatta

Country

India

Facility Name

1237.6.91007 Boehringer Ingelheim Investigational Site

City

Maharastra

Country

India

Facility Name

1237.6.91006 Boehringer Ingelheim Investigational Site

City

Mumbai

Country

India

Facility Name

1237.6.91009 Boehringer Ingelheim Investigational Site

City

Nashik, Maharashtra

Country

India

Facility Name

1237.6.91008 Boehringer Ingelheim Investigational Site

City

Pune

Country

India

Facility Name

1237.6.35304 Boehringer Ingelheim Investigational Site

City

County Limerick

Country

Ireland

Facility Name

1237.6.35303 Boehringer Ingelheim Investigational Site

City

Dublin 24

Country

Ireland

Facility Name

1237.6.35301 Boehringer Ingelheim Investigational Site

City

Dublin 4

Country

Ireland

Facility Name

1237.6.81127 Boehringer Ingelheim Investigational Site

City

Abeno-ku, Osaka, Osaka

Country

Japan

Facility Name

1237.6.81123 Boehringer Ingelheim Investigational Site

City

Aoi-ku, Shizuoka, Shizuoka

Country

Japan

Facility Name

1237.6.81132 Boehringer Ingelheim Investigational Site

City

Chuo-ku, Kobe, Hyogo

Country

Japan

Facility Name

1237.6.81121 Boehringer Ingelheim Investigational Site

City

Fukui, Fukui

Country

Japan

Facility Name

1237.6.81137 Boehringer Ingelheim Investigational Site

City

Fukuyama, Hiroshima

Country

Japan

Facility Name

1237.6.81109 Boehringer Ingelheim Investigational Site

City

Hachioji, Tokyo

Country

Japan

Facility Name

1237.6.81134 Boehringer Ingelheim Investigational Site

City

Himeji, Hyogo

Country

Japan

Facility Name

1237.6.81106 Boehringer Ingelheim Investigational Site

City

Hitachi, Ibaraki

Country

Japan

Facility Name

1237.6.81139 Boehringer Ingelheim Investigational Site

City

Iizuka, Fukuoka

Country

Japan

Facility Name

1237.6.81102 Boehringer Ingelheim Investigational Site

City

Iwamizawa, Hokkaido

Country

Japan

Facility Name

1237.6.81117 Boehringer Ingelheim Investigational Site

City

Kamakura, Kanagawa

Country

Japan

Facility Name

1237.6.81120 Boehringer Ingelheim Investigational Site

City

Kanazawa, Ishikawa

Country

Japan

Facility Name

1237.6.81113 Boehringer Ingelheim Investigational Site

City

Kanazawa, Yokohama, Kanagawa

Country

Japan

Facility Name

1237.6.81108 Boehringer Ingelheim Investigational Site

City

Kashiwa, Chiba

Country

Japan

Facility Name

1237.6.81114 Boehringer Ingelheim Investigational Site

City

Kawasaki-ku, Kawasaki, Kanagawa

Country

Japan

Facility Name

1237.6.81135 Boehringer Ingelheim Investigational Site

City

Kita-ku, Okayama, Okayama

Country

Japan

Facility Name

1237.6.81126 Boehringer Ingelheim Investigational Site

City

Kita-ku, Sakai, Osaka

Country

Japan

Facility Name

1237.6.81101 Boehringer Ingelheim Investigational Site

City

Kita-ku, Sapporo, Hokkaido

Country

Japan

Facility Name

1237.6.81136 Boehringer Ingelheim Investigational Site

City

Kurashiki, Okayama

Country

Japan

Facility Name

1237.6.81116 Boehringer Ingelheim Investigational Site

City

Minami-ku, Yokohama, Kanagawa

Country

Japan

Facility Name

1237.6.81118 Boehringer Ingelheim Investigational Site

City

Minami-ku, Yokohama, Kanagawa

Country

Japan

Facility Name

1237.6.81112 Boehringer Ingelheim Investigational Site

City

Mitaka, Tokyo

Country

Japan

Facility Name

1237.6.81105 Boehringer Ingelheim Investigational Site

City

Mito, Ibaraki

Country

Japan

Facility Name

1237.6.81142 Boehringer Ingelheim Investigational Site

City

Naha, Okinawa

Country

Japan

Facility Name

1237.6.81131 Boehringer Ingelheim Investigational Site

City

Nishi-ku, Kobe, Hyogo

Country

Japan

Facility Name

1237.6.81104 Boehringer Ingelheim Investigational Site

City

Obihiro, Hokkaido

Country

Japan

Facility Name

1237.6.81141 Boehringer Ingelheim Investigational Site

City

Okinawa, Okinawa

Country

Japan

Facility Name

1237.6.81110 Boehringer Ingelheim Investigational Site

City

Ota-ku, Tokyo

Country

Japan

Facility Name

1237.6.81138 Boehringer Ingelheim Investigational Site

City

Sakaide, Kagawa

Country

Japan

Facility Name

1237.6.81103 Boehringer Ingelheim Investigational Site

City

Sapporo, Hokkaido

Country

Japan

Facility Name

1237.6.81140 Boehringer Ingelheim Investigational Site

City

Shimajiri-gun, Okinawa

Country

Japan

Facility Name

1237.6.81144 Boehringer Ingelheim Investigational Site

City

Shimajiri-gun, Okinawa

Country

Japan

Facility Name

1237.6.81111 Boehringer Ingelheim Investigational Site

City

Shinjuku-ku, Tokyo

Country

Japan

Facility Name

1237.6.81145 Boehringer Ingelheim Investigational Site

City

Shinjuku-ku, Tokyo

Country

Japan

Facility Name

1237.6.81107 Boehringer Ingelheim Investigational Site

City

Soka, Saitama

Country

Japan

Facility Name

1237.6.81133 Boehringer Ingelheim Investigational Site

City

Takarazuka, Hyogo

Country

Japan

Facility Name

1237.6.81122 Boehringer Ingelheim Investigational Site

City

Takayama, Gifu

Country

Japan

Facility Name

1237.6.81143 Boehringer Ingelheim Investigational Site

City

Tomigusuku, Okinawa

Country

Japan

Facility Name

1237.6.81128 Boehringer Ingelheim Investigational Site

City

Toyonaka, Osaka

Country

Japan

Facility Name

1237.6.81124 Boehringer Ingelheim Investigational Site

City

Uji, Kyoto

Country

Japan

Facility Name

1237.6.81130 Boehringer Ingelheim Investigational Site

City

Yabu, Hyogo

Country

Japan

Facility Name

1237.6.81129 Boehringer Ingelheim Investigational Site

City

Yao, Osaka

Country

Japan

Facility Name

1237.6.81119 Boehringer Ingelheim Investigational Site

City

Yokosuka, Kanagawa

Country

Japan

Facility Name

1237.6.47005 Boehringer Ingelheim Investigational Site

City

Elverum

Country

Norway

Facility Name

1237.6.47001 Boehringer Ingelheim Investigational Site

City

Hønefoss

Country

Norway

Facility Name

1237.6.47002 Boehringer Ingelheim Investigational Site

City

Kløfta

Country

Norway

Facility Name

1237.6.47004 Boehringer Ingelheim Investigational Site

City

Lierskogen

Country

Norway

Facility Name

1237.6.47003 Boehringer Ingelheim Investigational Site

City

Oslo

Country

Norway

Facility Name

1237.6.47007 Boehringer Ingelheim Investigational Site

City

SKI

Country

Norway

Facility Name

1237.6.47008 Boehringer Ingelheim Investigational Site

City

Svelvik

Country

Norway

Facility Name

1237.6.40004 Boehringer Ingelheim Investigational Site

City

Arad

Country

Romania

Facility Name

1237.6.40005 Boehringer Ingelheim Investigational Site

City

Arad

Country

Romania

Facility Name

1237.6.40001 Boehringer Ingelheim Investigational Site

City

Bucharest

Country

Romania

Facility Name

1237.6.40002 Boehringer Ingelheim Investigational Site

City

Bucuresti

Country

Romania

Facility Name

1237.6.40003 Boehringer Ingelheim Investigational Site

City

Cluj

Country

Romania

Facility Name

1237.6.07004 Boehringer Ingelheim Investigational Site

City

Moscow

Country

Russian Federation

Facility Name

1237.6.07005 Boehringer Ingelheim Investigational Site

City

Moscow

Country

Russian Federation

Facility Name

1237.6.07002 Boehringer Ingelheim Investigational Site

City

St. Petersburg

Country

Russian Federation

Facility Name

1237.6.07003 Boehringer Ingelheim Investigational Site

City

St. Petersburg

Country

Russian Federation

Facility Name

1237.6.07001 Boehringer Ingelheim Investigational Site

City

Yaroslavl

Country

Russian Federation

Facility Name

1237.6.38103 Boehringer Ingelheim Investigational Site

City

Belgrade

Country

Serbia

Facility Name

1237.6.38104 Boehringer Ingelheim Investigational Site

City

Belgrade

Country

Serbia

Facility Name

1237.6.38105 Boehringer Ingelheim Investigational Site

City

Belgrade

Country

Serbia

Facility Name

1237.6.38102 Boehringer Ingelheim Investigational Site

City

Kragujevac

Country

Serbia

Facility Name

1237.6.38101 Boehringer Ingelheim Investigational Site

City

Nis

Country

Serbia

Facility Name

1237.6.42101 Boehringer Ingelheim Investigational Site

City

Bardejov

Country

Slovakia

Facility Name

1237.6.42102 Boehringer Ingelheim Investigational Site

City

Bojnice

Country

Slovakia

Facility Name

1237.6.42104 Boehringer Ingelheim Investigational Site

City

Kosice

Country

Slovakia

Facility Name

1237.6.42107 Boehringer Ingelheim Investigational Site

City

Nitra

Country

Slovakia

Facility Name

1237.6.42103 Boehringer Ingelheim Investigational Site

City

Spisska Nova Ves

Country

Slovakia

Facility Name

1237.6.42106 Boehringer Ingelheim Investigational Site

City

Zilina

Country

Slovakia

Facility Name

1237.6.27002 Boehringer Ingelheim Investigational Site

City

Bellville

Country

South Africa

Facility Name

1237.6.27001 Boehringer Ingelheim Investigational Site

City

Cape Town

Country

South Africa

Facility Name

1237.6.27003 Boehringer Ingelheim Investigational Site

City

Cape Town

Country

South Africa

Facility Name

1237.6.27004 Boehringer Ingelheim Investigational Site

City

Cape Town

Country

South Africa

Facility Name

1237.6.27005 Boehringer Ingelheim Investigational Site

City

Pretoria

Country

South Africa

Facility Name

1237.6.34008 Boehringer Ingelheim Investigational Site

City

Badalona (Barcelona)

Country

Spain

Facility Name

1237.6.34003 Boehringer Ingelheim Investigational Site

City

Barcelona

Country

Spain

Facility Name

1237.6.34009 Boehringer Ingelheim Investigational Site

City

Barcelona

Country

Spain

Facility Name

1237.6.34001 Boehringer Ingelheim Investigational Site

City

Hospitalet de Llobregat

Country

Spain

Facility Name

1237.6.34002 Boehringer Ingelheim Investigational Site

City

Mérida

Country

Spain

Facility Name

1237.6.34005 Boehringer Ingelheim Investigational Site

City

Pozuelo de Alarcón

Country

Spain

Facility Name

1237.6.34004 Boehringer Ingelheim Investigational Site

City

San Juan de Alicante

Country

Spain

Facility Name

1237.6.34006 Boehringer Ingelheim Investigational Site

City

Vic (Barcelona)

Country

Spain

Facility Name

1237.6.46003 Boehringer Ingelheim Investigational Site

City

Boden

Country

Sweden

Facility Name

1237.6.46002 Boehringer Ingelheim Investigational Site

City

Göteborg

Country

Sweden

Facility Name

1237.6.46006 Boehringer Ingelheim Investigational Site

City

Härnösand

Country

Sweden

Facility Name

1237.6.46005 Boehringer Ingelheim Investigational Site

City

Höllviken

Country

Sweden

Facility Name

1237.6.46001 Boehringer Ingelheim Investigational Site

City

Lund

Country

Sweden

Facility Name

1237.6.46004 Boehringer Ingelheim Investigational Site

City

Stockholm

Country

Sweden

Facility Name

1237.6.46007 Boehringer Ingelheim Investigational Site

City

Uddevalla

Country

Sweden

Facility Name

1237.6.88607 Boehringer Ingelheim Investigational Site

City

Kaohsiung City

Country

Taiwan

Facility Name

1237.6.88608 Boehringer Ingelheim Investigational Site

City

Kaohsiung

Country

Taiwan

Facility Name

1237.6.88602 Boehringer Ingelheim Investigational Site

City

New Taipei City

Country

Taiwan

Facility Name

1237.6.88604 Boehringer Ingelheim Investigational Site

City

Taichung

Country

Taiwan

Facility Name

1237.6.88605 Boehringer Ingelheim Investigational Site

City

Tainan

Country

Taiwan

Facility Name

1237.6.88601 Boehringer Ingelheim Investigational Site

City

Taipei

Country

Taiwan

Facility Name

1237.6.88603 Boehringer Ingelheim Investigational Site

City

Taoyuan County

Country

Taiwan

Facility Name

1237.6.90105 Boehringer Ingelheim Investigational Site

City

Ankara

Country

Turkey

Facility Name

1237.6.90103 Boehringer Ingelheim Investigational Site

City

Denizli

Country

Turkey

Facility Name

1237.6.90104 Boehringer Ingelheim Investigational Site

City

Istanbul

Country

Turkey

Facility Name

1237.6.90101 Boehringer Ingelheim Investigational Site

City

Izmir

Country

Turkey

Facility Name

1237.6.90102 Boehringer Ingelheim Investigational Site

City

Izmir

Country

Turkey

Facility Name

1237.6.44002 Boehringer Ingelheim Investigational Site

City

Blackpool

Country

United Kingdom

Facility Name

1237.6.44009 Boehringer Ingelheim Investigational Site

City

Blackpool

Country

United Kingdom

Facility Name

1237.6.44007 Boehringer Ingelheim Investigational Site

City

Bristol

Country

United Kingdom

Facility Name

1237.6.44010 Boehringer Ingelheim Investigational Site

City

Chertsey

Country

United Kingdom

Facility Name

1237.6.44011 Boehringer Ingelheim Investigational Site

City

Fleetwood

Country

United Kingdom

Facility Name

1237.6.44001 Boehringer Ingelheim Investigational Site

City

Manchester

Country

United Kingdom

Facility Name

1237.6.44008 Boehringer Ingelheim Investigational Site

City

Midsomer Norton

Country

United Kingdom

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

derived

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.

Results Reference

derived

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.

Results Reference

derived

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.

Results Reference

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