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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-010669-22 | EudraCT Number | EudraCT |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tiotropium+olodaterol high dose FDC | Experimental | Once daily 2 puffs solution for inhalation Respimat |
|
| tiotropium+olodaterol low dose FDC | Experimental | Once daily 2 puffs solution for inhalation Respimat |
|
| olodaterol | Active Comparator | Once daily 2 puffs solution for inhalation Respimat |
|
| tiotropium low dose | Active Comparator | Once daily 2 puffs solution for inhalation Respimat |
|
| tiotropium high dose | Active Comparator | Once daily 2 puffs solution for inhalation Respimat |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tiotropium + olodaterol | Drug | fixed dose combination |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| 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. | 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 |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1237.6.01106 Boehringer Ingelheim Investigational Site | Greer | California | United States | |||
| 1237.6.01120 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33175291 | Derived | 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. | |
| 32943047 |
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This trial was one of 2 confirmatory Phase III 52-week, multi-centre, multi-national, randomised, double-blind, parallel group studies to evaluate the long-term efficacy and safety of once daily treatment with orally inhaled Tio+Olo FDC (2.5/5μg; 5/5μg) compared with the individual components (2.5μg; 5μg Tiotropium, 5μg Olodaterol) in COPD patients
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| ID | Title | Description |
|---|---|---|
| FG000 | Olodaterol (5 μg) | Oral inhalation of Olodaterol 5 μg (2.5 μg per actuation), 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| FG001 | Tiotropium (2.5 μg) | Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| tiotropium + olodaterol |
| Drug |
fixed dose combination |
|
| tiotropium | Drug | low dose or high dose |
|
| tiotropium | Drug | low dose or high dose |
|
| olodaterol | Drug | one dose only |
|
| Respimat | Device | Respimat inhaler |
|
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. |
| Day 169 |
| Day 169 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Trough FEV1 Response on Day 43 | 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. | 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 |
| Trough FEV1 Response on Day 85 | 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. | 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 |
| Trough FEV1 Response on Day 169 | 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. | 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 |
| Trough FEV1 Response on Day 365 | 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. | 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 |
| 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. | 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 |
| Forced Vital Capacity (FVC) 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Trough FVC Response on Day 43 | 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. | 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 |
| Trough FVC Response on Day 85 | 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. | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and 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. | 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 |
| Trough FVC Response on Day 365 | 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. | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 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. | Day 85 |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 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. | Day 365 |
| 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. | Day 43 |
| 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. | Day 85 |
| 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. | Day 365 |
| Fort Collins |
| Colorado |
| United States |
| 1237.6.01131 Boehringer Ingelheim Investigational Site | Danbury | Connecticut | United States |
| 1237.6.01117 Boehringer Ingelheim Investigational Site | Waterbury | Connecticut | United States |
| 1237.6.01118 Boehringer Ingelheim Investigational Site | DeLand | Florida | United States |
| 1237.6.01126 Boehringer Ingelheim Investigational Site | Tampa | Florida | United States |
| 1237.6.01109 Boehringer Ingelheim Investigational Site | Winter Park | Florida | United States |
| 1237.6.01134 Boehringer Ingelheim Investigational Site | Atlanta | Georgia | United States |
| 1237.6.01107 Boehringer Ingelheim Investigational Site | Couer d'Alene | Idaho | United States |
| 1237.6.01110 Boehringer Ingelheim Investigational Site | Lafayette | Louisiana | United States |
| 1237.6.01128 Boehringer Ingelheim Investigational Site | Baltimore | Maryland | United States |
| 1237.6.01130 Boehringer Ingelheim Investigational Site | North Dartmouth | Massachusetts | United States |
| 1237.6.01104 Boehringer Ingelheim Investigational Site | Minneapolis | Minnesota | United States |
| 1237.6.01116 Boehringer Ingelheim Investigational Site | Plymouth | Minnesota | United States |
| 1237.6.01121 Boehringer Ingelheim Investigational Site | St Louis | Missouri | United States |
| 1237.6.01123 Boehringer Ingelheim Investigational Site | St Louis | Missouri | United States |
| 1237.6.01129 Boehringer Ingelheim Investigational Site | Henderson | Nevada | United States |
| 1237.6.01136 Boehringer Ingelheim Investigational Site | Marlton | New Jersey | United States |
| 1237.6.01108 Boehringer Ingelheim Investigational Site | Albuquerque | New Mexico | United States |
| 1237.6.01127 Boehringer Ingelheim Investigational Site | Bayside | New York | United States |
| 1237.6.01139 Boehringer Ingelheim Investigational Site | Great Neck | New York | United States |
| 1237.6.01135 Boehringer Ingelheim Investigational Site | Charlotte | North Carolina | United States |
| 1237.6.01114 Boehringer Ingelheim Investigational Site | Cincinnati | Ohio | United States |
| 1237.6.01102 Boehringer Ingelheim Investigational Site | Columbus | Ohio | United States |
| 1237.6.01115 Boehringer Ingelheim Investigational Site | Oklahoma City | Oklahoma | United States |
| 1237.6.01101 Boehringer Ingelheim Investigational Site | Philadelphia | Pennsylvania | United States |
| 1237.6.01113 Boehringer Ingelheim Investigational Site | East Providence | Rhode Island | United States |
| 1237.6.01122 Boehringer Ingelheim Investigational Site | Charleston | South Carolina | United States |
| 1237.6.01132 Boehringer Ingelheim Investigational Site | Greenville | South Carolina | United States |
| 1237.6.01137 Boehringer Ingelheim Investigational Site | Greenville | South Carolina | United States |
| 1237.6.01111 Boehringer Ingelheim Investigational Site | Spartanburg | South Carolina | United States |
| 1237.6.01105 Boehringer Ingelheim Investigational Site | Union | South Carolina | United States |
| 1237.6.01138 Boehringer Ingelheim Investigational Site | Killeen | Texas | United States |
| 1237.6.01124 Boehringer Ingelheim Investigational Site | McKinney | Texas | United States |
| 1237.6.01112 Boehringer Ingelheim Investigational Site | Richmond | Virginia | United States |
| 1237.6.01133 Boehringer Ingelheim Investigational Site | Richmond | Virginia | United States |
| 1237.6.01125 Boehringer Ingelheim Investigational Site | Spokane | Washington | United States |
| 1237.6.01103 Boehringer Ingelheim Investigational Site | Tacoma | Washington | United States |
| 1237.6.43006 Boehringer Ingelheim Investigational Site | Feldbach | Austria |
| 1237.6.43005 Boehringer Ingelheim Investigational Site | Gänserndorf | Austria |
| 1237.6.43002 Boehringer Ingelheim Investigational Site | Innsbruck | Austria |
| 1237.6.43004 Boehringer Ingelheim Investigational Site | Leoben | Austria |
| 1237.6.43001 Boehringer Ingelheim Investigational Site | Linz | Austria |
| 1237.6.43003 Boehringer Ingelheim Investigational Site | Salzburg | Austria |
| 1237.6.32005 Boehringer Ingelheim Investigational Site | Brussels | Belgium |
| 1237.6.32007 Boehringer Ingelheim Investigational Site | Brussels | Belgium |
| 1237.6.32004 Boehringer Ingelheim Investigational Site | Ghent | Belgium |
| 1237.6.32002 Boehringer Ingelheim Investigational Site | Jambes | Belgium |
| 1237.6.32009 Boehringer Ingelheim Investigational Site | Lebbeke | Belgium |
| 1237.6.32001 Boehringer Ingelheim Investigational Site | Leuven | Belgium |
| 1237.6.32006 Boehringer Ingelheim Investigational Site | Liège | Belgium |
| 1237.6.32008 Boehringer Ingelheim Investigational Site | Ostend | Belgium |
| 1237.6.32010 Boehringer Ingelheim Investigational Site | Turnhout | Belgium |
| 1237.6.55013 Boehringer Ingelheim Investigational Site | Botucatu | Brazil |
| 1237.6.55010 Boehringer Ingelheim Investigational Site | Florianópolis | Brazil |
| 1237.6.55012 Boehringer Ingelheim Investigational Site | Passo Fundo | Brazil |
| 1237.6.55001 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1237.6.55002 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1237.6.55003 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1237.6.55005 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1237.6.55009 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 1237.6.55006 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 1237.6.55007 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 1237.6.55011 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 1237.6.02109 Boehringer Ingelheim Investigational Site | Edmonton | Alberta | Canada |
| 1237.6.02111 Boehringer Ingelheim Investigational Site | Vancouver | British Columbia | Canada |
| 1237.6.02106 Boehringer Ingelheim Investigational Site | Moncton | New Brunswick | Canada |
| 1237.6.02110 Boehringer Ingelheim Investigational Site | Courtice | Ontario | Canada |
| 1237.6.02101 Boehringer Ingelheim Investigational Site | Downsview | Ontario | Canada |
| 1237.6.02112 Boehringer Ingelheim Investigational Site | Sarnia | Ontario | Canada |
| 1237.6.02103 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada |
| 1237.6.02102 Boehringer Ingelheim Investigational Site | Windsor | Ontario | Canada |
| 1237.6.02104 Boehringer Ingelheim Investigational Site | Point Claire | Quebec | Canada |
| 1237.6.02105 Boehringer Ingelheim Investigational Site | Sherbrooke | Quebec | Canada |
| 1237.6.02108 Boehringer Ingelheim Investigational Site | Ste-Foy | Quebec | Canada |
| 1237.6.86117 Boehringer Ingelheim Investigational Site | Baotou | China |
| 1237.6.86102 Boehringer Ingelheim Investigational Site | Beijing | China |
| 1237.6.86104 Boehringer Ingelheim Investigational Site | Beijing | China |
| 1237.6.86105 Boehringer Ingelheim Investigational Site | Beijing | China |
| 1237.6.86115 Boehringer Ingelheim Investigational Site | Changsha | China |
| 1237.6.86110 Boehringer Ingelheim Investigational Site | Chengdu | China |
| 1237.6.86111 Boehringer Ingelheim Investigational Site | Chongqing | China |
| 1237.6.86109 Boehringer Ingelheim Investigational Site | Haikou | China |
| 1237.6.86108 Boehringer Ingelheim Investigational Site | Hangzhou | China |
| 1237.6.86116 Boehringer Ingelheim Investigational Site | Hohhot | China |
| 1237.6.86114 Boehringer Ingelheim Investigational Site | Jinan | China |
| 1237.6.86106 Boehringer Ingelheim Investigational Site | Nanjing | China |
| 1237.6.86101 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 1237.6.86113 Boehringer Ingelheim Investigational Site | Shenyang | China |
| 1237.6.86107 Boehringer Ingelheim Investigational Site | Suzhou | China |
| 1237.6.86112 Boehringer Ingelheim Investigational Site | Xi'an | China |
| 1237.6.57001 Boehringer Ingelheim Investigational Site | Bogota DC | Colombia |
| 1237.6.57003 Boehringer Ingelheim Investigational Site | Bogota DC | Colombia |
| 1237.6.57007 Boehringer Ingelheim Investigational Site | Bogota DC | Colombia |
| 1237.6.57008 Boehringer Ingelheim Investigational Site | Bogotá | Colombia |
| 1237.6.57006 Boehringer Ingelheim Investigational Site | Cali | Colombia |
| 1237.6.57004 Boehringer Ingelheim Investigational Site | Floridablanca | Colombia |
| 1237.6.38503 Boehringer Ingelheim Investigational Site | Petrinja | Croatia |
| 1237.6.38504 Boehringer Ingelheim Investigational Site | Rijeka | Croatia |
| 1237.6.38502 Boehringer Ingelheim Investigational Site | Zadar | Croatia |
| 1237.6.38501 Boehringer Ingelheim Investigational Site | Zagreb | Croatia |
| 1237.6.49022 Boehringer Ingelheim Investigational Site | Aschaffenburg | Germany |
| 1237.6.49017 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1237.6.49026 Boehringer Ingelheim Investigational Site | Frankfurt | Germany |
| 1237.6.49027 Boehringer Ingelheim Investigational Site | Frankfurt | Germany |
| 1237.6.49025 Boehringer Ingelheim Investigational Site | Großhansdorf | Germany |
| 1237.6.49016 Boehringer Ingelheim Investigational Site | Halle | Germany |
| 1237.6.49024 Boehringer Ingelheim Investigational Site | Hamburg | Germany |
| 1237.6.49021 Boehringer Ingelheim Investigational Site | Hanover | Germany |
| 1237.6.49019 Boehringer Ingelheim Investigational Site | Leipzig | Germany |
| 1237.6.49028 Boehringer Ingelheim Investigational Site | Mainz | Germany |
| 1237.6.49018 Boehringer Ingelheim Investigational Site | Rodgau/Dudenhofen | Germany |
| 1237.6.49020 Boehringer Ingelheim Investigational Site | Schwerin | Germany |
| 1237.6.49023 Boehringer Ingelheim Investigational Site | Teuchern | Germany |
| 1237.6.36001 Boehringer Ingelheim Investigational Site | Debrecen | Hungary |
| 1237.6.36004 Boehringer Ingelheim Investigational Site | Gödöllö | Hungary |
| 1237.6.36005 Boehringer Ingelheim Investigational Site | Pécs | Hungary |
| 1237.6.36003 Boehringer Ingelheim Investigational Site | Sopron | Hungary |
| 1237.6.36002 Boehringer Ingelheim Investigational Site | Szeged | Hungary |
| 1237.6.91003 Boehringer Ingelheim Investigational Site | Chennai | India |
| 1237.6.91011 Boehringer Ingelheim Investigational Site | Coimbatore | India |
| 1237.6.91004 Boehringer Ingelheim Investigational Site | Jaipur | India |
| 1237.6.91002 Boehringer Ingelheim Investigational Site | Kolkata | India |
| 1237.6.91007 Boehringer Ingelheim Investigational Site | Maharastra | India |
| 1237.6.91006 Boehringer Ingelheim Investigational Site | Mumbai | India |
| 1237.6.91009 Boehringer Ingelheim Investigational Site | Nashik, Maharashtra | India |
| 1237.6.91008 Boehringer Ingelheim Investigational Site | Pune | India |
| 1237.6.35304 Boehringer Ingelheim Investigational Site | County Limerick | Ireland |
| 1237.6.35301 Boehringer Ingelheim Investigational Site | Dublin | Ireland |
| 1237.6.35303 Boehringer Ingelheim Investigational Site | Dublin | Ireland |
| 1237.6.81127 Boehringer Ingelheim Investigational Site | Abeno-ku, Osaka, Osaka | Japan |
| 1237.6.81123 Boehringer Ingelheim Investigational Site | Aoi-ku, Shizuoka, Shizuoka | Japan |
| 1237.6.81132 Boehringer Ingelheim Investigational Site | Chuo-ku, Kobe, Hyogo | Japan |
| 1237.6.81121 Boehringer Ingelheim Investigational Site | Fukui, Fukui | Japan |
| 1237.6.81137 Boehringer Ingelheim Investigational Site | Fukuyama, Hiroshima | Japan |
| 1237.6.81109 Boehringer Ingelheim Investigational Site | Hachioji, Tokyo | Japan |
| 1237.6.81134 Boehringer Ingelheim Investigational Site | Himeji, Hyogo | Japan |
| 1237.6.81106 Boehringer Ingelheim Investigational Site | Hitachi, Ibaraki | Japan |
| 1237.6.81139 Boehringer Ingelheim Investigational Site | Iizuka, Fukuoka | Japan |
| 1237.6.81102 Boehringer Ingelheim Investigational Site | Iwamizawa, Hokkaido | Japan |
| 1237.6.81117 Boehringer Ingelheim Investigational Site | Kamakura, Kanagawa | Japan |
| 1237.6.81120 Boehringer Ingelheim Investigational Site | Kanazawa, Ishikawa | Japan |
| 1237.6.81113 Boehringer Ingelheim Investigational Site | Kanazawa, Yokohama, Kanagawa | Japan |
| 1237.6.81108 Boehringer Ingelheim Investigational Site | Kashiwa, Chiba | Japan |
| 1237.6.81114 Boehringer Ingelheim Investigational Site | Kawasaki-ku, Kawasaki, Kanagawa | Japan |
| 1237.6.81135 Boehringer Ingelheim Investigational Site | Kita-ku, Okayama, Okayama | Japan |
| 1237.6.81126 Boehringer Ingelheim Investigational Site | Kita-ku, Sakai, Osaka | Japan |
| 1237.6.81101 Boehringer Ingelheim Investigational Site | Kita-ku, Sapporo, Hokkaido | Japan |
| 1237.6.81136 Boehringer Ingelheim Investigational Site | Kurashiki, Okayama | Japan |
| 1237.6.81116 Boehringer Ingelheim Investigational Site | Minami-ku, Yokohama, Kanagawa | Japan |
| 1237.6.81118 Boehringer Ingelheim Investigational Site | Minami-ku, Yokohama, Kanagawa | Japan |
| 1237.6.81112 Boehringer Ingelheim Investigational Site | Mitaka, Tokyo | Japan |
| 1237.6.81105 Boehringer Ingelheim Investigational Site | Mito, Ibaraki | Japan |
| 1237.6.81142 Boehringer Ingelheim Investigational Site | Naha, Okinawa | Japan |
| 1237.6.81131 Boehringer Ingelheim Investigational Site | Nishi-ku, Kobe, Hyogo | Japan |
| 1237.6.81104 Boehringer Ingelheim Investigational Site | Obihiro, Hokkaido | Japan |
| 1237.6.81141 Boehringer Ingelheim Investigational Site | Okinawa, Okinawa | Japan |
| 1237.6.81110 Boehringer Ingelheim Investigational Site | Ota-ku, Tokyo | Japan |
| 1237.6.81138 Boehringer Ingelheim Investigational Site | Sakaide, Kagawa | Japan |
| 1237.6.81103 Boehringer Ingelheim Investigational Site | Sapporo, Hokkaido | Japan |
| 1237.6.81140 Boehringer Ingelheim Investigational Site | Shimajiri-gun, Okinawa | Japan |
| 1237.6.81144 Boehringer Ingelheim Investigational Site | Shimajiri-gun, Okinawa | Japan |
| 1237.6.81111 Boehringer Ingelheim Investigational Site | Shinjuku-ku, Tokyo | Japan |
| 1237.6.81145 Boehringer Ingelheim Investigational Site | Shinjuku-ku, Tokyo | Japan |
| 1237.6.81107 Boehringer Ingelheim Investigational Site | Soka, Saitama | Japan |
| 1237.6.81133 Boehringer Ingelheim Investigational Site | Takarazuka, Hyogo | Japan |
| 1237.6.81122 Boehringer Ingelheim Investigational Site | Takayama, Gifu | Japan |
| 1237.6.81143 Boehringer Ingelheim Investigational Site | Tomigusuku, Okinawa | Japan |
| 1237.6.81128 Boehringer Ingelheim Investigational Site | Toyonaka, Osaka | Japan |
| 1237.6.81124 Boehringer Ingelheim Investigational Site | Uji, Kyoto | Japan |
| 1237.6.81130 Boehringer Ingelheim Investigational Site | Yabu, Hyogo | Japan |
| 1237.6.81129 Boehringer Ingelheim Investigational Site | Yao, Osaka | Japan |
| 1237.6.81119 Boehringer Ingelheim Investigational Site | Yokosuka, Kanagawa | Japan |
| 1237.6.47005 Boehringer Ingelheim Investigational Site | Elverum | Norway |
| 1237.6.47001 Boehringer Ingelheim Investigational Site | Hønefoss | Norway |
| 1237.6.47002 Boehringer Ingelheim Investigational Site | Kløfta | Norway |
| 1237.6.47004 Boehringer Ingelheim Investigational Site | Lierskogen | Norway |
| 1237.6.47003 Boehringer Ingelheim Investigational Site | Oslo | Norway |
| 1237.6.47007 Boehringer Ingelheim Investigational Site | Ski | Norway |
| 1237.6.47008 Boehringer Ingelheim Investigational Site | Svelvik | Norway |
| 1237.6.40004 Boehringer Ingelheim Investigational Site | Arad | Romania |
| 1237.6.40005 Boehringer Ingelheim Investigational Site | Arad | Romania |
| 1237.6.40001 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 1237.6.40002 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 1237.6.40003 Boehringer Ingelheim Investigational Site | Cluj-Napoca | Romania |
| 1237.6.07004 Boehringer Ingelheim Investigational Site | Moscow | Russia |
| 1237.6.07005 Boehringer Ingelheim Investigational Site | Moscow | Russia |
| 1237.6.07002 Boehringer Ingelheim Investigational Site | Saint Petersburg | Russia |
| 1237.6.07003 Boehringer Ingelheim Investigational Site | Saint Petersburg | Russia |
| 1237.6.07001 Boehringer Ingelheim Investigational Site | Yaroslavl | Russia |
| 1237.6.38103 Boehringer Ingelheim Investigational Site | Belgrade | Serbia |
| 1237.6.38104 Boehringer Ingelheim Investigational Site | Belgrade | Serbia |
| 1237.6.38105 Boehringer Ingelheim Investigational Site | Belgrade | Serbia |
| 1237.6.38102 Boehringer Ingelheim Investigational Site | Kragujevac | Serbia |
| 1237.6.38101 Boehringer Ingelheim Investigational Site | Niš | Serbia |
| 1237.6.42101 Boehringer Ingelheim Investigational Site | Bardejov | Slovakia |
| 1237.6.42102 Boehringer Ingelheim Investigational Site | Bojnice | Slovakia |
| 1237.6.42104 Boehringer Ingelheim Investigational Site | Košice | Slovakia |
| 1237.6.42107 Boehringer Ingelheim Investigational Site | Nitra | Slovakia |
| 1237.6.42103 Boehringer Ingelheim Investigational Site | Spišská Nová Ves | Slovakia |
| 1237.6.42106 Boehringer Ingelheim Investigational Site | Žilina | Slovakia |
| 1237.6.27002 Boehringer Ingelheim Investigational Site | Bellville | South Africa |
| 1237.6.27001 Boehringer Ingelheim Investigational Site | Cape Town | South Africa |
| 1237.6.27003 Boehringer Ingelheim Investigational Site | Cape Town | South Africa |
| 1237.6.27004 Boehringer Ingelheim Investigational Site | Cape Town | South Africa |
| 1237.6.27005 Boehringer Ingelheim Investigational Site | Pretoria | South Africa |
| 1237.6.34008 Boehringer Ingelheim Investigational Site | Badalona (Barcelona) | Spain |
| 1237.6.34003 Boehringer Ingelheim Investigational Site | Barcelona | Spain |
| 1237.6.34009 Boehringer Ingelheim Investigational Site | Barcelona | Spain |
| 1237.6.34001 Boehringer Ingelheim Investigational Site | L'Hospitalet de Llobregat | Spain |
| 1237.6.34002 Boehringer Ingelheim Investigational Site | Mérida | Spain |
| 1237.6.34005 Boehringer Ingelheim Investigational Site | Pozuelo de Alarcón | Spain |
| 1237.6.34004 Boehringer Ingelheim Investigational Site | Sant Joan d'Alacant | Spain |
| 1237.6.34006 Boehringer Ingelheim Investigational Site | Vic (Barcelona) | Spain |
| 1237.6.46003 Boehringer Ingelheim Investigational Site | Boden | Sweden |
| 1237.6.46002 Boehringer Ingelheim Investigational Site | Gothenburg | Sweden |
| 1237.6.46006 Boehringer Ingelheim Investigational Site | Härnösand | Sweden |
| 1237.6.46005 Boehringer Ingelheim Investigational Site | Höllviken | Sweden |
| 1237.6.46001 Boehringer Ingelheim Investigational Site | Lund | Sweden |
| 1237.6.46004 Boehringer Ingelheim Investigational Site | Stockholm | Sweden |
| 1237.6.46007 Boehringer Ingelheim Investigational Site | Uddevalla | Sweden |
| 1237.6.88607 Boehringer Ingelheim Investigational Site | Kaohsiung City | Taiwan |
| 1237.6.88608 Boehringer Ingelheim Investigational Site | Kaohsiung City | Taiwan |
| 1237.6.88602 Boehringer Ingelheim Investigational Site | New Taipei City | Taiwan |
| 1237.6.88604 Boehringer Ingelheim Investigational Site | Taichung | Taiwan |
| 1237.6.88605 Boehringer Ingelheim Investigational Site | Tainan | Taiwan |
| 1237.6.88601 Boehringer Ingelheim Investigational Site | Taipei | Taiwan |
| 1237.6.88603 Boehringer Ingelheim Investigational Site | Taoyuan County | Taiwan |
| 1237.6.90105 Boehringer Ingelheim Investigational Site | Ankara | Turkey (Türkiye) |
| 1237.6.90103 Boehringer Ingelheim Investigational Site | Denizli | Turkey (Türkiye) |
| 1237.6.90104 Boehringer Ingelheim Investigational Site | Istanbul | Turkey (Türkiye) |
| 1237.6.90101 Boehringer Ingelheim Investigational Site | Izmir | Turkey (Türkiye) |
| 1237.6.90102 Boehringer Ingelheim Investigational Site | Izmir | Turkey (Türkiye) |
| 1237.6.44002 Boehringer Ingelheim Investigational Site | Blackpool | United Kingdom |
| 1237.6.44009 Boehringer Ingelheim Investigational Site | Blackpool | United Kingdom |
| 1237.6.44007 Boehringer Ingelheim Investigational Site | Bristol | United Kingdom |
| 1237.6.44010 Boehringer Ingelheim Investigational Site | Chertsey | United Kingdom |
| 1237.6.44011 Boehringer Ingelheim Investigational Site | Fleetwood | United Kingdom |
| 1237.6.44001 Boehringer Ingelheim Investigational Site | Manchester | United Kingdom |
| 1237.6.44008 Boehringer Ingelheim Investigational Site | Midsomer Norton | United Kingdom |
| Derived |
| 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. |
| 32848380 | Derived | 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. |
| 32848379 | Derived | 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. |
| 32776202 | Derived | 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. |
| 32671684 | Derived | 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. |
| 32462607 | Derived | 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. |
| 30261995 | Derived | 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. |
| 29355547 | Derived | 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. |
| 27993292 | Derived | 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. |
| 26112656 | Derived | 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. |
| 25573406 | Derived | 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. |
| FG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| FG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| FG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| COMPLETED |
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| NOT COMPLETED |
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Treated set (TS): This patient set included all patients in the randomised set who were dispensed study medication and were documented to have taken any dose of study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Olodaterol (5 μg) | Oral inhalation of Olodaterol 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| BG001 | Tiotropium (2.5 μg) | Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| BG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| BG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| BG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | The Full analysis set (FAS) included all patients who were randomised, who were dispensed study medication, were documented to have taken any dose of study medication and who had a non-missing baseline and at least one non-missing post-baseline measurement before or at Week 24 for any of the primary and key secondary efficacy endpoints. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Primary | 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. | FAS. Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Primary | 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. | FAS. Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 169 |
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| Secondary | 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. | FAS. Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 169 |
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| Secondary | 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. | FAS. Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (on day 85). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (on day 365). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (day 15). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | Trough FEV1 Response on Day 43 | 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. | FAS (day 43). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | Trough FEV1 Response on Day 85 | 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. | FAS (day 85). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | Trough FEV1 Response on Day 169 | 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. | FAS (day 169). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | Trough FEV1 Response on Day 365 | 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. | FAS (day 365). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (day 1). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Median | Standard Error | Litres | 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 |
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| Secondary | Forced Vital Capacity (FVC) 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. | FAS (day 85). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Median | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (day 169). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Median | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (day 365). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Median | Standard Error | Litres | 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 |
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| Secondary | 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. | FAS (day 15). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | Trough FVC Response on Day 43 | 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. | FAS (day 43). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
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| Secondary | Trough FVC Response on Day 85 | 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. | FAS (day 85). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85 |
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| Secondary | 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. | FAS. Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Trough FVC Response on Day 365 | 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. | FAS (day 365). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | Litres | 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 365 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | 12 hr PFT set: All patients who have given Informed Consent for the 12-hour PFT testing and had any spirometry measurement after 3-hour and before or at 12-hours post-dose on Days 169 and 170. | Posted | Least Squares Mean | Standard Error | Litres | 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | 12-hr PFT set | Posted | Least Squares Mean | Standard Error | Litres | 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | 12-hr PFT set | Posted | Least Squares Mean | Standard Error | Litres | 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | 12-hr PFT set | Posted | Least Squares Mean | Standard Error | Litres | 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 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. | FAS (day 85). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 85 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 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. | FAS (day 365). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 365 |
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| Secondary | 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. | FAS (day 43). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 43 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | FAS (day 85). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 85 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | FAS (day 365). Since it is possible for the patient to meet the data criterion for only a subset of the primary endpoints, it is possible that the number of patients used in the FAS analysis for different endpoints will vary. | Posted | Least Squares Mean | Standard Error | points on a scale | Day 365 |
|
All Adverse events with an onset after the first dose of study medication up to a period of 21 days after the last dose of study medication were assigned to the treatment period for evaluation (Up to 459 days)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Olodaterol (5 μg) | Oral inhalation of Olodaterol 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. | 106 | 510 | 246 | 510 | ||
| EG001 | Tiotropium (2.5 μg) | Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. | 90 | 507 | 228 | 507 | ||
| EG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. | 93 | 506 | 216 | 506 | ||
| EG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. | 87 | 508 | 223 | 508 | ||
| EG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. | 82 | 507 | 214 | 507 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemorrhagic anaemia | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Aortic valve stenosis | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac disorder | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Extrasystoles | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ischaemic cardiomyopathy | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Tachyarrhythmia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Malformation biliary | Congenital, familial and genetic disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Age-related macular degeneration | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Macular degeneration | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Retinal tear | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Crohn's disease | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Diverticulum intestinal | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Duodenal ulcer perforation | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Inguinal hernia strangulated | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Mesenteric artery stenosis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Oesophageal achalasia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Oesophageal stenosis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Death | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Device dislocation | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Drowning | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Generalised oedema | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Medical device complication | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Multi-organ failure | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Sudden death | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Biliary colic | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Anti-neutrophil cytoplasmic antibody positive vasculitis | Immune system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abscess | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Anal abscess | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Appendicitis perforated | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Biliary sepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Bronchopneumonia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Cellulitis pharyngeal | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Dermatitis infected | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Graft infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| H1N1 influenza | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Infective exacerbation of chronic obstructive airways disease | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Ophthalmic herpes zoster | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pelvic abscess | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumococcal sepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Post procedural infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Postoperative abscess | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Superinfection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Abdominal injury | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Acetabulum fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Avulsion fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Liver contusion | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Patella fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Skull fractured base | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Stab wound | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Tendon rupture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Traumatic haematoma | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Vascular pseudoaneurysm | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Blood pressure decreased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Troponin T increased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bone deformity | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Foot deformity | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Monarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Periarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Spinal column stenosis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Spondylolisthesis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Synovial cyst | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Bladder neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Bronchial carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Colon adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Hepatic cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung adenocarcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Metastases to adrenals | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Neoplasm prostate | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Neuroendocrine carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Oesophageal squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Oropharyngeal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Penile cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Prostate cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Squamous cell carcinoma of lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Squamous cell carcinoma of the tongue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Sweat gland tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Acute polyneuropathy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Carotid artery aneurysm | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Carotid artery stenosis | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cerebellar haemorrhage | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cerebrovascular disorder | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypoxic-ischaemic encephalopathy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Neuromyopathy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Spondylitic myelopathy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Thrombotic cerebral infarction | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Acute stress disorder | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bipolar I disorder | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Conversion disorder | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Major depression | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nephritis | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal vasculitis | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vaginal prolapse | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Analgesic asthma syndrome | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bullous lung disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Emphysema | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hydrothorax | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypercapnia | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nasal polyps | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nasal turbinate hypertrophy | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary granuloma | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary infarction | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Rhonchi | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vocal cord polyp | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Aneurysm | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Aortic aneurysm | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Aortic aneurysm rupture | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Arteritis | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Intermittent claudication | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Leriche syndrome | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Peripheral artery aneurysm | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Peripheral artery stenosis | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Shock | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Thrombophlebitis | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000611386 | tiotropium-olodaterol |
| D000069447 | Tiotropium Bromide |
| C549647 | olodaterol |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
Not provided
Not provided
| Male |
|
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | 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 a random effect. | Adjusted mean difference | 0.103 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.078 | 0.127 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | < 0.0001 | 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 a random effect. | Adjusted mean difference | 0.121 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.096 | 0.145 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | 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 a random effect. | Adjusted mean difference | 0.131 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.106 | 0.155 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | 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 a random effect. | Adjusted mean difference | 0.091 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.066 | 0.115 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.3394 | 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 a random effect. | Adjusted mean difference | 0.012 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | -0.013 | 0.036 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | <0.0001 | 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 a random effect. | Adjusted mean difference | 0.143 | Standard Error of the Mean | 0.013 | 2-Sided | 95 | 0.118 | 0.167 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.0173 | 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 a random effect. | Adjusted mean difference | 0.030 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.005 | 0.054 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.4210 | 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 a random effect. | Adjusted mean difference | -0.010 | Standard Error of the Mean | 0.013 | 2-Sided | 95 | -0.035 | 0.014 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.0014 | 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 a random effect. | Adjusted mean difference | 0.040 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.015 | 0.064 | spatial power covariance structure for within-patient errors | No | Superiority or Other |
| Tiotropium (2.5 μg) |
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
|
|
|
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
|
|
|
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
|
|
|
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
|
|
|
| Tiotropium (2.5 μg) |
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (2.5 μg) |
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning.
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning.
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning.
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning.
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning.
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (2.5 μg) |
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (2.5 μg) |
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning.
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning.
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning.
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (2.5 μg) |
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning. |
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation), 2 puffs in the morning.
| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (5 μg) |
Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (5 μg) |
Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| Tiotropium (5 μg) |
Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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| OG002 | Tiotropium (5 μg) | Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation), 2 puffs in the morning. |
| OG003 | Tio+Olo FDC (2.5/5 μg) | Oral inhalation of FDC of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
| OG004 | Tio+Olo FDC (5/5 μg) | Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation), 2 puffs in the morning. |
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