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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-010668-40 | 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 Chronic Obstructive Pulmonary Disease (COPD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tiotropium+olodaterol low dose FDC | Experimental | Once daily 2 puffs solution for inhalation Respimat |
|
| tiotropium+olodaterol high dose FDC | Experimental | Once daily 2 puffs solution for inhalation Respimat |
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| olodaterol | Active Comparator | Once daily 2 puffs solution for inhalation Respimat |
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| 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) |
| Measure | Description | Time Frame |
|---|---|---|
| Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) is the key secondary endpoint. The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. |
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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 |
|---|---|---|---|---|---|---|
| 1237.5.01038 Boehringer Ingelheim Investigational Site | Jasper | Alabama | United States | |||
| 1237.5.01036 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 |
| Drug |
low dose |
|
| olodaterol | Drug | one dose only |
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| tiotropium | Drug | high dose |
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| tiotropium + olodaterol | Drug | fixed dose combination |
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| 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 1 hr 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 1 hr 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 |
| FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1 | FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. | 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. |
| FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85 | FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. | 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. |
| FVC (Forced Vital Capacity) 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. |
| FVC (Forced Vital Capacity) 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 23 h and at 23 h 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 the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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 the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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 the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | Day 85 |
| Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | Day 365 |
| Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 43 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | Day 43 |
| Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 85 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | Day 85 |
| Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 365 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | Day 365 |
| Mobile |
| Alabama |
| United States |
| 1237.5.01015 Boehringer Ingelheim Investigational Site | Boulder | Colorado | United States |
| 1237.5.01024 Boehringer Ingelheim Investigational Site | Wheat Ridge | Colorado | United States |
| 1237.5.01034 Boehringer Ingelheim Investigational Site | Stamford | Connecticut | United States |
| 1237.5.01003 Boehringer Ingelheim Investigational Site | Clearwater | Florida | United States |
| 1237.5.01010 Boehringer Ingelheim Investigational Site | Clearwater | Florida | United States |
| 1237.5.01027 Boehringer Ingelheim Investigational Site | Panama City | Florida | United States |
| 1237.5.01031 Boehringer Ingelheim Investigational Site | O'Fallon | Illinois | United States |
| 1237.5.01035 Boehringer Ingelheim Investigational Site | Opelousas | Louisiana | United States |
| 1237.5.01004 Boehringer Ingelheim Investigational Site | Shreveport | Louisiana | United States |
| 1237.5.01017 Boehringer Ingelheim Investigational Site | Biddeford | Maine | United States |
| 1237.5.01028 Boehringer Ingelheim Investigational Site | Columbia | Maryland | United States |
| 1237.5.01013 Boehringer Ingelheim Investigational Site | Livonia | Michigan | United States |
| 1237.5.01019 Boehringer Ingelheim Investigational Site | Omaha | Nebraska | United States |
| 1237.5.01025 Boehringer Ingelheim Investigational Site | Larchmont | New York | United States |
| 1237.5.01008 Boehringer Ingelheim Investigational Site | Rochester | New York | United States |
| 1237.5.01023 Boehringer Ingelheim Investigational Site | Raleigh | North Carolina | United States |
| 1237.5.01016 Boehringer Ingelheim Investigational Site | Tabor City | North Carolina | United States |
| 1237.5.01006 Boehringer Ingelheim Investigational Site | Cincinnati | Ohio | United States |
| 1237.5.01040 Boehringer Ingelheim Investigational Site | Columbus | Ohio | United States |
| 1237.5.01039 Boehringer Ingelheim Investigational Site | Dayton | Ohio | United States |
| 1237.5.01037 Boehringer Ingelheim Investigational Site | Toledo | Ohio | United States |
| 1237.5.01009 Boehringer Ingelheim Investigational Site | Oklahoma City | Oklahoma | United States |
| 1237.5.01032 Boehringer Ingelheim Investigational Site | Charleston | Pennsylvania | United States |
| 1237.5.01005 Boehringer Ingelheim Investigational Site | Johnston | Rhode Island | United States |
| 1237.5.01021 Boehringer Ingelheim Investigational Site | Easley | South Carolina | United States |
| 1237.5.01012 Boehringer Ingelheim Investigational Site | Gaffney | South Carolina | United States |
| 1237.5.01014 Boehringer Ingelheim Investigational Site | Spartanburg | South Carolina | United States |
| 1237.5.01029 Boehringer Ingelheim Investigational Site | Fort Worth | Texas | United States |
| 1237.5.01002 Boehringer Ingelheim Investigational Site | San Antonio | Texas | United States |
| 1237.5.01026 Boehringer Ingelheim Investigational Site | Lynchburg | Virginia | United States |
| 1237.5.01007 Boehringer Ingelheim Investigational Site | Spokane | Washington | United States |
| 1237.5.01033 Boehringer Ingelheim Investigational Site | Tacoma | Washington | United States |
| 1237.5.01001 Boehringer Ingelheim Investigational Site | Morgantown | West Virginia | United States |
| 1237.5.54010 Boehringer Ingelheim Investigational Site | Buenos Aires | Argentina |
| 1237.5.54013 Boehringer Ingelheim Investigational Site | Caba | Argentina |
| 1237.5.54016 Boehringer Ingelheim Investigational Site | Caba | Argentina |
| 1237.5.54003 Boehringer Ingelheim Investigational Site | Capital Federal | Argentina |
| 1237.5.54002 Boehringer Ingelheim Investigational Site | Cuidad Autonoma de Buenos Airess A | Argentina |
| 1237.5.54006 Boehringer Ingelheim Investigational Site | Mar del Plata | Argentina |
| 1237.5.54007 Boehringer Ingelheim Investigational Site | Mar del Plata | Argentina |
| 1237.5.54009 Boehringer Ingelheim Investigational Site | Mendoza | Argentina |
| 1237.5.54012 Boehringer Ingelheim Investigational Site | Monte Grande | Argentina |
| 1237.5.54008 Boehringer Ingelheim Investigational Site | Quilmes | Argentina |
| 1237.5.54005 Boehringer Ingelheim Investigational Site | Rosario | Argentina |
| 1237.5.54004 Boehringer Ingelheim Investigational Site | San Miguel de Tucuma | Argentina |
| 1237.5.54011 Boehringer Ingelheim Investigational Site | San Miguel de Tucumán | Argentina |
| 1237.5.61001 Boehringer Ingelheim Investigational Site | Toorak Gardens | South Australia | Australia |
| 1237.5.61002 Boehringer Ingelheim Investigational Site | Woodville | South Australia | Australia |
| 1237.5.61004 Boehringer Ingelheim Investigational Site | Frankston | Victoria | Australia |
| 1237.5.35905 Boehringer Ingelheim Investigational Site | Plovdiv | Bulgaria |
| 1237.5.35901 Boehringer Ingelheim Investigational Site | Rousse | Bulgaria |
| 1237.5.35906 Boehringer Ingelheim Investigational Site | Shumen | Bulgaria |
| 1237.5.35902 Boehringer Ingelheim Investigational Site | Sofia | Bulgaria |
| 1237.5.35904 Boehringer Ingelheim Investigational Site | Sofia | Bulgaria |
| 1237.5.35903 Boehringer Ingelheim Investigational Site | Troyan Municipality | Bulgaria |
| 1237.5.35908 Boehringer Ingelheim Investigational Site | Veliko Tarnovo | Bulgaria |
| 1237.5.02002 Boehringer Ingelheim Investigational Site | Calgary | Alberta | Canada |
| 1237.5.02001 Boehringer Ingelheim Investigational Site | Vancouver | British Columbia | Canada |
| 1237.5.02004 Boehringer Ingelheim Investigational Site | Winnipeg | Manitoba | Canada |
| 1237.5.02005 Boehringer Ingelheim Investigational Site | Burlington | Ontario | Canada |
| 1237.5.02007 Boehringer Ingelheim Investigational Site | Grimsby | Ontario | Canada |
| 1237.5.02011 Boehringer Ingelheim Investigational Site | Ottawa | Ontario | Canada |
| 1237.5.02003 Boehringer Ingelheim Investigational Site | Québec | Quebec | Canada |
| 1237.5.02006 Boehringer Ingelheim Investigational Site | Québec | Quebec | Canada |
| 1237.5.02008 Boehringer Ingelheim Investigational Site | Sherbrooke | Quebec | Canada |
| 1237.5.02009 Boehringer Ingelheim Investigational Site | Saskatoon | Saskatchewan | Canada |
| 1237.5.86003 Boehringer Ingelheim Investigational Site | Beijing | China |
| 1237.5.86004 Boehringer Ingelheim Investigational Site | Beijing | China |
| 1237.5.86011 Boehringer Ingelheim Investigational Site | Changsha | China |
| 1237.5.86012 Boehringer Ingelheim Investigational Site | Changsha | China |
| 1237.5.86014 Boehringer Ingelheim Investigational Site | Foshan | China |
| 1237.5.86001 Boehringer Ingelheim Investigational Site | Guangzhou | China |
| 1237.5.86015 Boehringer Ingelheim Investigational Site | Nanning | China |
| 1237.5.86002 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 1237.5.86005 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 1237.5.86006 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 1237.5.86007 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 1237.5.86009 Boehringer Ingelheim Investigational Site | Shenyang | China |
| 1237.5.86016 Boehringer Ingelheim Investigational Site | Wuhan | China |
| 1237.5.86010 Boehringer Ingelheim Investigational Site | Xi'an | China |
| 1237.5.86008 Boehringer Ingelheim Investigational Site | Yangzhou | China |
| 1237.5.86017 Boehringer Ingelheim Investigational Site | Yinchuan | China |
| 1237.5.42004 Boehringer Ingelheim Investigational Site | Beroun | Czechia |
| 1237.5.42002 Boehringer Ingelheim Investigational Site | Cvikov | Czechia |
| 1237.5.42001 Boehringer Ingelheim Investigational Site | Prague | Czechia |
| 1237.5.42005 Boehringer Ingelheim Investigational Site | Rokycany | Czechia |
| 1237.5.42003 Boehringer Ingelheim Investigational Site | Znojmo | Czechia |
| 1237.5.45002 Boehringer Ingelheim Investigational Site | Aalborg | Denmark |
| 1237.5.45009 Boehringer Ingelheim Investigational Site | Hvidovre | Denmark |
| 1237.5.45007 Boehringer Ingelheim Investigational Site | Kolding | Denmark |
| 1237.5.45001 Boehringer Ingelheim Investigational Site | København NV | Denmark |
| 1237.5.45011 Boehringer Ingelheim Investigational Site | Næstved | Denmark |
| 1237.5.45006 Boehringer Ingelheim Investigational Site | Odense C | Denmark |
| 1237.5.45008 Boehringer Ingelheim Investigational Site | Roskilde | Denmark |
| 1237.5.45003 Boehringer Ingelheim Investigational Site | Silkeborg | Denmark |
| 1237.5.45005 Boehringer Ingelheim Investigational Site | Sønderborg | Denmark |
| 1237.5.45004 Boehringer Ingelheim Investigational Site | Vaerløse | Denmark |
| 1237.5.37002 Boehringer Ingelheim Investigational Site | Tallinn | Estonia |
| 1237.5.37001 Boehringer Ingelheim Investigational Site | Tartu | Estonia |
| 1237.5.35801 Boehringer Ingelheim Investigational Site | Helsinki | Finland |
| 1237.5.35804 Boehringer Ingelheim Investigational Site | Pori | Finland |
| 1237.5.35802 Boehringer Ingelheim Investigational Site | Turku | Finland |
| 1237.5.33004 Boehringer Ingelheim Investigational Site | Béthune | France |
| 1237.5.33007 Boehringer Ingelheim Investigational Site | Montpellier | France |
| 1237.5.33005 Boehringer Ingelheim Investigational Site | Nantes | France |
| 1237.5.33006 Boehringer Ingelheim Investigational Site | Nîmes | France |
| 1237.5.33008 Boehringer Ingelheim Investigational Site | Perpignan | France |
| 1237.5.33001 Boehringer Ingelheim Investigational Site | Saint-Pierre | France |
| 1237.5.33002 Boehringer Ingelheim Investigational Site | Strasbourg | France |
| 1237.5.49006 Boehringer Ingelheim Investigational Site | Bamberg | Germany |
| 1237.5.49002 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1237.5.49003 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1237.5.49013 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1237.5.49011 Boehringer Ingelheim Investigational Site | Erfurt | Germany |
| 1237.5.49005 Boehringer Ingelheim Investigational Site | Hamburg | Germany |
| 1237.5.49010 Boehringer Ingelheim Investigational Site | Hamburg | Germany |
| 1237.5.49009 Boehringer Ingelheim Investigational Site | Koblenz | Germany |
| 1237.5.49014 Boehringer Ingelheim Investigational Site | Neu-Isenburg | Germany |
| 1237.5.49012 Boehringer Ingelheim Investigational Site | Oschersleben | Germany |
| 1237.5.49001 Boehringer Ingelheim Investigational Site | Rüdersdorf | Germany |
| 1237.5.49004 Boehringer Ingelheim Investigational Site | Weinheim | Germany |
| 1237.5.49008 Boehringer Ingelheim Investigational Site | Wiesloch | Germany |
| 1237.5.50201 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.50202 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.50203 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.50204 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.50205 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.50206 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.50207 Boehringer Ingelheim Investigational Site | Guatemala City | Guatemala |
| 1237.5.36005 Boehringer Ingelheim Investigational Site | Debrecen | Hungary |
| 1237.5.36001 Boehringer Ingelheim Investigational Site | Deszk | Hungary |
| 1237.5.36006 Boehringer Ingelheim Investigational Site | Kapuvár | Hungary |
| 1237.5.36003 Boehringer Ingelheim Investigational Site | Szombathely | Hungary |
| 1237.5.36002 Boehringer Ingelheim Investigational Site | Törökbálint | Hungary |
| 1237.5.91010 Boehringer Ingelheim Investigational Site | Ahmedabad | India |
| 1237.5.91002 Boehringer Ingelheim Investigational Site | Bangalore | India |
| 1237.5.91007 Boehringer Ingelheim Investigational Site | Bangalore | India |
| 1237.5.91004 Boehringer Ingelheim Investigational Site | Coimbatore | India |
| 1237.5.91011 Boehringer Ingelheim Investigational Site | Hyderabad | India |
| 1237.5.91001 Boehringer Ingelheim Investigational Site | Jaipur | India |
| 1237.5.91008 Boehringer Ingelheim Investigational Site | Jaipur | India |
| 1237.5.91009 Boehringer Ingelheim Investigational Site | Mysore | India |
| 1237.5.91006 Boehringer Ingelheim Investigational Site | Pune | India |
| 1237.5.39008 Boehringer Ingelheim Investigational Site | Cagliari | Italy |
| 1237.5.39002 Boehringer Ingelheim Investigational Site | Genova | Italy |
| 1237.5.39006 Boehringer Ingelheim Investigational Site | Montescano (PV) | Italy |
| 1237.5.39009 Boehringer Ingelheim Investigational Site | Monza | Italy |
| 1237.5.39004 Boehringer Ingelheim Investigational Site | Parma | Italy |
| 1237.5.39001 Boehringer Ingelheim Investigational Site | Pisa | Italy |
| 1237.5.81003 Boehringer Ingelheim Investigational Site | Aoba-ku, Sendai, Miyagi | Japan |
| 1237.5.81001 Boehringer Ingelheim Investigational Site | Asahikawa, Hokkaido | Japan |
| 1237.5.81006 Boehringer Ingelheim Investigational Site | Bunkyo-ku, Tokyo | Japan |
| 1237.5.81044 Boehringer Ingelheim Investigational Site | Chuo-ku, Kumamoto, Kumamoto | Japan |
| 1237.5.81035 Boehringer Ingelheim Investigational Site | Gifu, Gifu | Japan |
| 1237.5.81017 Boehringer Ingelheim Investigational Site | Hakata-ku, Fukuoka, Fukuoka | Japan |
| 1237.5.81031 Boehringer Ingelheim Investigational Site | Hamamatsushi, Shizuoka | Japan |
| 1237.5.81014 Boehringer Ingelheim Investigational Site | Himeji, Hyogo | Japan |
| 1237.5.81037 Boehringer Ingelheim Investigational Site | Ikoma, Nara | Japan |
| 1237.5.81024 Boehringer Ingelheim Investigational Site | Inashiki-gun, Ibaraki | Japan |
| 1237.5.81008 Boehringer Ingelheim Investigational Site | Itabashi-ku, Tokyo | Japan |
| 1237.5.81016 Boehringer Ingelheim Investigational Site | Jonan-ku, Fukuoka, Fukuoka | Japan |
| 1237.5.81020 Boehringer Ingelheim Investigational Site | Kagoshima, Kagoshima, | Japan |
| 1237.5.81021 Boehringer Ingelheim Investigational Site | Kagoshima, Kagoshima | Japan |
| 1237.5.81005 Boehringer Ingelheim Investigational Site | Kamogawa, Chiba | Japan |
| 1237.5.81011 Boehringer Ingelheim Investigational Site | Kishiwada, Osaka | Japan |
| 1237.5.81018 Boehringer Ingelheim Investigational Site | Kitakyusyu,Fukuoka | Japan |
| 1237.5.81042 Boehringer Ingelheim Investigational Site | Koga, Fukuoka | Japan |
| 1237.5.81032 Boehringer Ingelheim Investigational Site | Komaki, Aichi | Japan |
| 1237.5.81033 Boehringer Ingelheim Investigational Site | Komaki, Aichi | Japan |
| 1237.5.81019 Boehringer Ingelheim Investigational Site | Koshi, Kumamoto | Japan |
| 1237.5.81027 Boehringer Ingelheim Investigational Site | Koto-ku, Tokyo | Japan |
| 1237.5.81025 Boehringer Ingelheim Investigational Site | Kuki, Saitama | Japan |
| 1237.5.81038 Boehringer Ingelheim Investigational Site | Kure, Hiroshima | Japan |
| 1237.5.81015 Boehringer Ingelheim Investigational Site | Kurume, Fukuoka | Japan |
| 1237.5.81029 Boehringer Ingelheim Investigational Site | Matsumoto, Nagano | Japan |
| 1237.5.81030 Boehringer Ingelheim Investigational Site | Matsumoto, Nagano | Japan |
| 1237.5.81010 Boehringer Ingelheim Investigational Site | Matsusaka, Mie | Japan |
| 1237.5.81041 Boehringer Ingelheim Investigational Site | Minami-ku. Fukuoka, Fukuoka | Japan |
| 1237.5.81002 Boehringer Ingelheim Investigational Site | Morioka, Iwate | Japan |
| 1237.5.81034 Boehringer Ingelheim Investigational Site | Nagoya, Aichi | Japan |
| 1237.5.81036 Boehringer Ingelheim Investigational Site | Nagoya, Aichi | Japan |
| 1237.5.81004 Boehringer Ingelheim Investigational Site | Naka-gun, Ibaraki | Japan |
| 1237.5.81022 Boehringer Ingelheim Investigational Site | Okinawa, Urasoe | Japan |
| 1237.5.81023 Boehringer Ingelheim Investigational Site | Okinawa, Urasoe | Japan |
| 1237.5.81012 Boehringer Ingelheim Investigational Site | Sayama, Osaka | Japan |
| 1237.5.81045 Boehringer Ingelheim Investigational Site | Sendai, Miyagi | Japan |
| 1237.5.81009 Boehringer Ingelheim Investigational Site | Seto, Aichi | Japan |
| 1237.5.81026 Boehringer Ingelheim Investigational Site | Shinagawa, Tokyo | Japan |
| 1237.5.81007 Boehringer Ingelheim Investigational Site | Shinjyuku-ku, Tokyo | Japan |
| 1237.5.81039 Boehringer Ingelheim Investigational Site | Takamatsu, Kagawa | Japan |
| 1237.5.81040 Boehringer Ingelheim Investigational Site | Takamatsu, Kagawa | Japan |
| 1237.5.81013 Boehringer Ingelheim Investigational Site | Wakayama, Wakayama | Japan |
| 1237.5.81043 Boehringer Ingelheim Investigational Site | Yanagawa-shi, Fukuoka, | Japan |
| 1237.5.81028 Boehringer Ingelheim Investigational Site | Yokohama, Kanagawa | Japan |
| 1237.5.52002 Boehringer Ingelheim Investigational Site | Hermosillo | Mexico |
| 1237.5.52003 Boehringer Ingelheim Investigational Site | México | Mexico |
| 1237.5.52007 Boehringer Ingelheim Investigational Site | Monterrey | Mexico |
| 1237.5.52001 Boehringer Ingelheim Investigational Site | Tijuana | Mexico |
| 1237.5.31004 Boehringer Ingelheim Investigational Site | Almelo | Netherlands |
| 1237.5.31006 Boehringer Ingelheim Investigational Site | Breda | Netherlands |
| 1237.5.31001 Boehringer Ingelheim Investigational Site | Eindhoven | Netherlands |
| 1237.5.31008 Boehringer Ingelheim Investigational Site | Harderwijk | Netherlands |
| 1237.5.31007 Boehringer Ingelheim Investigational Site | Heerlen | Netherlands |
| 1237.5.31010 Boehringer Ingelheim Investigational Site | Hengelo | Netherlands |
| 1237.5.31009 Boehringer Ingelheim Investigational Site | Hoorn | Netherlands |
| 1237.5.31005 Boehringer Ingelheim Investigational Site | Nieuwegein | Netherlands |
| 1237.5.31002 Boehringer Ingelheim Investigational Site | Veldhoven | Netherlands |
| 1237.5.31003 Boehringer Ingelheim Investigational Site | Zutphen | Netherlands |
| 1237.5.64002 Boehringer Ingelheim Investigational Site | Dunedin | New Zealand |
| 1237.5.64001 Boehringer Ingelheim Investigational Site | Greenlane East Auckland NZ | New Zealand |
| 1237.5.35105 Boehringer Ingelheim Investigational Site | Amadora | Portugal |
| 1237.5.35101 Boehringer Ingelheim Investigational Site | Coimbra | Portugal |
| 1237.5.35102 Boehringer Ingelheim Investigational Site | Lisbon | Portugal |
| 1237.5.35104 Boehringer Ingelheim Investigational Site | Lisbon | Portugal |
| 1237.5.35103 Boehringer Ingelheim Investigational Site | Porto | Portugal |
| 1237.5.35106 Boehringer Ingelheim Investigational Site | Vila Nova de Gaia | Portugal |
| 1237.5.35107 Boehringer Ingelheim Investigational Site | Viseu | Portugal |
| 1237.5.07001 Boehringer Ingelheim Investigational Site | Gatchina (Leningradskaya Oblast) | Russia |
| 1237.5.07003 Boehringer Ingelheim Investigational Site | Kazan' | Russia |
| 1237.5.07004 Boehringer Ingelheim Investigational Site | Moscow | Russia |
| 1237.5.07005 Boehringer Ingelheim Investigational Site | Moscow | Russia |
| 1237.5.07002 Boehringer Ingelheim Investigational Site | Saint Petersburg | Russia |
| 1237.5.38601 Boehringer Ingelheim Investigational Site | Golnik | Slovenia |
| 1237.5.38602 Boehringer Ingelheim Investigational Site | Golnik | Slovenia |
| 1237.5.82004 Boehringer Ingelheim Investigational Site | Bucheon-si | South Korea |
| 1237.5.82008 Boehringer Ingelheim Investigational Site | Daegu | South Korea |
| 1237.5.82001 Boehringer Ingelheim Investigational Site | Seoul | South Korea |
| 1237.5.82002 Boehringer Ingelheim Investigational Site | Seoul | South Korea |
| 1237.5.82003 Boehringer Ingelheim Investigational Site | Seoul | South Korea |
| 1237.5.82007 Boehringer Ingelheim Investigational Site | Seoul | South Korea |
| 1237.5.82005 Boehringer Ingelheim Investigational Site | Suwon | South Korea |
| 1237.5.82006 Boehringer Ingelheim Investigational Site | Wŏnju | South Korea |
| 1237.5.90003 Boehringer Ingelheim Investigational Site | Istanbul | Turkey (Türkiye) |
| 1237.5.90004 Boehringer Ingelheim Investigational Site | Istanbul | Turkey (Türkiye) |
| 1237.5.90002 Boehringer Ingelheim Investigational Site | Izmir | Turkey (Türkiye) |
| 1237.5.90005 Boehringer Ingelheim Investigational Site | İzmit | Turkey (Türkiye) |
| 1237.5.90001 Boehringer Ingelheim Investigational Site | Mersin | Turkey (Türkiye) |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) is the key secondary endpoint. The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | 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. 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 1 hr 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 1 hr 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 | FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1 | FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. | 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 | 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 | FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85 | FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. | 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 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 | FVC (Forced Vital Capacity) 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 | 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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| Secondary | FVC (Forced Vital Capacity) 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 | 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 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 23 h and at 23 h 50 min after inhalation of study medication on Day 170 |
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| 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 the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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. |
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| Secondary | FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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 the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group. | 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. |
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| Secondary | Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | 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 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 43 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | 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 |
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| Secondary | Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 85 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | FAS | Posted | Least Squares Mean | Standard Error | points on a scale | Day 85 |
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| Secondary | Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) | Mahler Transitional Dyspnoea Index (TDI) focal score on Day 365 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. | 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 447 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. | 75 | 528 | 221 | 528 | ||
| 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. | 66 | 525 | 207 | 525 | ||
| 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. | 79 | 527 | 210 | 527 | ||
| 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. | 81 | 522 | 211 | 522 | ||
| 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. | 87 | 522 | 193 | 522 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancytopenia | 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 |
| |
| Arteriosclerosis coronary artery | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Atrioventricular block | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac arrest | 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 chronic | 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 |
| |
| Cardiomyopathy | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiopulmonary failure | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Mitral valve stenosis | 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 |
| |
| Ventricular fibrillation | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hyperparathyroidism primary | Endocrine disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abdominal adhesions | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal 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 |
| |
| Anal fissure | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Coeliac disease | 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 |
| |
| Diverticular perforation | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Duodenitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastric polyps | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastric ulcer | 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 |
| |
| Haematemesis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Large intestine polyp | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatic cyst | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatic duct dilatation | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatitis chronic | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Rectal ulcer | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Umbilical hernia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Death | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Electrocution | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Generalised oedema | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hernia | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Inflammation | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Local swelling | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Malaise | 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 |
| |
| Sudden death | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Systemic inflammatory response syndrome | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Biliary dilatation | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
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| Cholangitis | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hepatic cyst | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Jaundice cholestatic | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
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| Bronchopneumonia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Extradural abscess | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Hepatitis E | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Infected bites | 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 |
| |
| Klebsiella sepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Lung abscess | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
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| Lung infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Otitis media chronic | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonia pneumococcal | 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 |
| |
| Staphylococcal sepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Bone fissure | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Brain contusion | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Cervical vertebral 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 |
| |
| Facial bones fracture | 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 |
| |
| Fractured coccyx | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Periprosthetic fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumothorax traumatic | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Post laminectomy syndrome | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Postoperative ileus | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Skull fractured base | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Subdural haemorrhage | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Tendon rupture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Arteriogram coronary | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Cardiac murmur | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Prostatic specific antigen increased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Failure to thrive | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypovolaemia | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Fascial hernia | 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 |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Osteoporosis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Spinal column stenosis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Adenocarcinoma pancreas | 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 |
| |
| Benign neoplasm of bladder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Benign ovarian tumour | 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 |
| |
| Bladder papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Brain 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 |
| |
| Chronic lymphocytic leukaemia | 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 |
| |
| Enchondroma | 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 |
| |
| Gastric neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Glioblastoma multiforme | 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 |
| |
| Lipoma | 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 malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Metastases to bone | 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 lymph nodes | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Neuroendocrine carcinoma of the skin | 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 |
| |
| Prostate 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 cell carcinoma | 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 |
| |
| Small cell lung cancer metastatic | 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 |
| |
| Tongue neoplasm malignant stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Ureteric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Amyotrophic lateral sclerosis | 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 |
| |
| Convulsion | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Critical illness polyneuropathy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cubital tunnel syndrome | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dementia | 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 |
| |
| Haemorrhagic stroke | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Intracranial aneurysm | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Lacunar infarction | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Lumbar radiculopathy | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Multiple sclerosis | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Post herpetic neuralgia | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vocal cord paralysis | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bipolar disorder | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Major depression | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Psychiatric decompensation | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Psychotic disorder | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Calculus ureteric | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal failure chronic | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Urethral stenosis | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pelvic adhesions | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Prostatomegaly | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Uterine prolapse | Reproductive system and breast disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemoptysis | 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 |
| |
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Organising pneumonia | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonitis | 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 congestion | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pulmonary hypertension | 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 distress | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Psoriasis | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hip arthroplasty | Surgical and medical procedures | MEDDRA 16.1 | Systematic Assessment |
| |
| Nasal septal operation | Surgical and medical procedures | MEDDRA 16.1 | Systematic Assessment |
| |
| Arterial occlusive disease | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Arteriosclerosis | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Deep vein thrombosis | 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 |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Peripheral vascular disorder | 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 |
|
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 | 0.117 | Standard Error of the Mean | 0.012 | 95 | 0.094 | 0.140 | Tio+Olo FDC (5/5 μg) versus Tiotropium (5 μg). 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 | 0.109 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.086 | 0.132 | Tio+Olo FDC (2.5/5 μg) versus Olodaterol (5 μg). 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 | 0.093 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.070 | 0.116 | Tio+Olo FDC (2.5/5 μg) versus Tiotropium (2.5 µg). 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 | 0.102 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.080 | 0.125 | Tio+Olo FDC (2.5/5 μg) versus Tiotropium (5 µg). Spatial power covariance structure for within-patient errors. | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.2169 | 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 | 0.014 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | -0.008 | 0.037 | Tio+Olo FDC (5/5 µg) versus Tio+Olo FDC (2.5/5 µg). 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 | 0.108 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | 0.085 | 0.130 | Tio+Olo FDC (5/5 µg) versus Tiotropium (2.5 µg). Spatial power covariance structure for within-patient errors. | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.5849 | 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 | 0.006 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | -0.017 | 0.029 | Tiotropium (5 µg) versus Olodaterol (5 µg). Spatial power covariance structure for within-patient errors. | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.1863 | 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 | 0.016 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | -0.007 | 0.039 | Tiotropium (2.5 µg) versus Olodaterol (5 µg). Spatial power covariance structure for within-patient errors. | No | Superiority or Other |
| Mixed Models Analysis | Kenward-Roger approximation of denominator degrees of freedom. | 0.4352 | 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 | -0.009 | Standard Error of the Mean | 0.012 | 2-Sided | 95 | -0.032 | 0.014 | Tiotropium (5 µg) versus Tiotropium (2.5 µg). Spatial power covariance structure for within-patient errors. | No | Superiority or Other |
| OG001 |
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
|
|
|
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
|
|
|
Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
|
|
|
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
|
|
|
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, 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 from the RESPIMAT inhaler, once daily, in the morning. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, 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 from the RESPIMAT inhaler, once daily, in the morning. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, 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 from the RESPIMAT inhaler, once daily, in the morning. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG001 |
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG001 |
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, 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 from the RESPIMAT inhaler, once daily, in the morning. |
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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| OG002 |
| 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
| OG002 | 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. |
| OG003 | 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. |
| 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 from the RESPIMAT inhaler, once daily, in the morning. |
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