Tiotropium+Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Registration Number
- NCT01431274
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The overall objective of this study is to assess the efficacy and safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the RESPIMAT Inhaler) compared with the individual components ( tiotropium, olodaterol) (delivered by the RESPIMAT Inhaler) in patients with Chronic Obstructive Pulmonary Disease (COPD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2624
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tiotropium+olodaterol low dose FDC tiotropium + olodaterol Once daily 2 puffs solution for inhalation Respimat tiotropium+olodaterol low dose FDC Respimat Once daily 2 puffs solution for inhalation Respimat tiotropium+olodaterol high dose FDC Respimat Once daily 2 puffs solution for inhalation Respimat olodaterol olodaterol Once daily 2 puffs solution for inhalation Respimat olodaterol Respimat Once daily 2 puffs solution for inhalation Respimat tiotropium low dose tiotropium Once daily 2 puffs solution for inhalation Respimat tiotropium low dose Respimat Once daily 2 puffs solution for inhalation Respimat tiotropium high dose tiotropium Once daily 2 puffs solution for inhalation Respimat tiotropium high dose Respimat Once daily 2 puffs solution for inhalation Respimat tiotropium+olodaterol high dose FDC tiotropium + olodaterol Once daily 2 puffs solution for inhalation Respimat
- Primary Outcome Measures
Name Time Method Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169. 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. FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the MMRM model in each treatment group.Trough FEV1 Response on Day 170. 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 FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FEV1 measurements performed at 23 h and at 23 h 50 min after inhalation of study medication at the clinic visit on the previous day.
Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 169 The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.
- Secondary Outcome Measures
Name Time Method Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 169 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.Trough FEV1 Response on Day 169 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 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed
1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Trough FEV1 Response on Day 365 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 Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed
1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1 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 AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.
FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85 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 AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.
FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169 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 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.FEV1 AUC(0-3h) Response on Day 1 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) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.
FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.FEV1 AUC(0-3h) Response on Day 85 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) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.FEV1 AUC(0-3h) Response on Day 365 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. FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Trough FEV1 Response on Day 15. 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 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed
1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Trough FEV1 Response on Day 43 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 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed
1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Trough FEV1 Response on Day 85 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 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed
1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365 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. FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.
FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Trough FVC Response on Day 15. 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 was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.Trough FVC Response on Day 43. 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 was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.
Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.
The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.Trough FVC Response on Day 85. 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and 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.Trough FVC Response on Day 170. 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 was defined as the FVC value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FVC measurements performed at 23h and at 23h 50 min after inhalation of study medication at the clinic visit on the previous day.
Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.Trough FVC Response on Day 365. 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and 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.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) 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(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.
Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) 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. FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.
Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.FVC AUC(0-12h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) 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(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.
FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.FVC AUC(0-24h) Response in Sub-set of Patients With 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) 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(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.
FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).
The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.
Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 85 The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 365 The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 43 Mahler Transitional Dyspnoea Index (TDI) focal score on Day 43 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).
The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 85 Mahler Transitional Dyspnoea Index (TDI) focal score on Day 85 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).
The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.
Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) Day 365 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.
Trial Locations
- Locations (239)
1237.5.01028 Boehringer Ingelheim Investigational Site
🇺🇸Columbia, Maryland, United States
1237.5.42005 Boehringer Ingelheim Investigational Site
🇨🇿Rokycany, Czech Republic
1237.5.35802 Boehringer Ingelheim Investigational Site
🇫🇮Turku, Finland
1237.5.52003 Boehringer Ingelheim Investigational Site
🇲🇽Mexico, Mexico
1237.5.86012 Boehringer Ingelheim Investigational Site
🇨🇳Changsha, China
1237.5.86009 Boehringer Ingelheim Investigational Site
🇨🇳Shenyang, China
1237.5.86016 Boehringer Ingelheim Investigational Site
🇨🇳Wuhan, China
1237.5.01037 Boehringer Ingelheim Investigational Site
🇺🇸Toledo, Ohio, United States
1237.5.01004 Boehringer Ingelheim Investigational Site
🇺🇸Shreveport, Louisiana, United States
1237.5.54013 Boehringer Ingelheim Investigational Site
🇦🇷Caba, Argentina
1237.5.54016 Boehringer Ingelheim Investigational Site
🇦🇷Caba, Argentina
1237.5.01023 Boehringer Ingelheim Investigational Site
🇺🇸Raleigh, North Carolina, United States
1237.5.01014 Boehringer Ingelheim Investigational Site
🇺🇸Spartanburg, South Carolina, United States
1237.5.01021 Boehringer Ingelheim Investigational Site
🇺🇸Easley, South Carolina, United States
1237.5.01035 Boehringer Ingelheim Investigational Site
🇺🇸Opelousas, Louisiana, United States
1237.5.01001 Boehringer Ingelheim Investigational Site
🇺🇸Morgantown, West Virginia, United States
1237.5.01015 Boehringer Ingelheim Investigational Site
🇺🇸Boulder, Colorado, United States
1237.5.01027 Boehringer Ingelheim Investigational Site
🇺🇸Panama City, Florida, 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
1237.5.01029 Boehringer Ingelheim Investigational Site
🇺🇸Ft. Worth, Texas, United States
1237.5.54006 Boehringer Ingelheim Investigational Site
🇦🇷Mar del Plata, Argentina
1237.5.01012 Boehringer Ingelheim Investigational Site
🇺🇸Gaffney, South Carolina, United States
1237.5.01040 Boehringer Ingelheim Investigational Site
🇺🇸Columbus, Ohio, United States
1237.5.01026 Boehringer Ingelheim Investigational Site
🇺🇸Lynchburg, Virginia, United States
1237.5.81025 Boehringer Ingelheim Investigational Site
🇯🇵Kuki, Saitama, Japan
1237.5.37001 Boehringer Ingelheim Investigational Site
🇪🇪Tartu, Estonia
1237.5.49005 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1237.5.33002 Boehringer Ingelheim Investigational Site
🇫🇷Strasbourg, France
1237.5.33001 Boehringer Ingelheim Investigational Site
🇫🇷Saint Pierre Cedex, France
1237.5.91009 Boehringer Ingelheim Investigational Site
🇮🇳Mysore, India
1237.5.33005 Boehringer Ingelheim Investigational Site
🇫🇷Nantes, France
1237.5.50201 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, Guatemala
1237.5.50202 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, Guatemala
1237.5.50203 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, Guatemala
1237.5.36002 Boehringer Ingelheim Investigational Site
🇭🇺Törökbalint, Hungary
1237.5.36003 Boehringer Ingelheim Investigational Site
🇭🇺Szombathely, Hungary
1237.5.91010 Boehringer Ingelheim Investigational Site
🇮🇳Ahmedabad, India
1237.5.49013 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.5.49001 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
1237.5.81014 Boehringer Ingelheim Investigational Site
🇯🇵Himeji, Hyogo, Japan
1237.5.50205 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, Guatemala
1237.5.50207 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, Guatemala
1237.5.39006 Boehringer Ingelheim Investigational Site
🇮🇹Montescano (PV), Italy
1237.5.49006 Boehringer Ingelheim Investigational Site
🇩🇪Bamberg, Germany
1237.5.81006 Boehringer Ingelheim Investigational Site
🇯🇵Bunkyo-ku, Tokyo, Japan
1237.5.33006 Boehringer Ingelheim Investigational Site
🇫🇷Nîmes cedex 9, France
1237.5.49009 Boehringer Ingelheim Investigational Site
🇩🇪Koblenz, Germany
1237.5.49011 Boehringer Ingelheim Investigational Site
🇩🇪Erfurt, Germany
1237.5.81023 Boehringer Ingelheim Investigational Site
🇯🇵Okinawa, Urasoe, Japan
1237.5.82004 Boehringer Ingelheim Investigational Site
🇰🇷Bucheon, Korea, Republic of
1237.5.81029 Boehringer Ingelheim Investigational Site
🇯🇵Matsumoto, Nagano, Japan
1237.5.31005 Boehringer Ingelheim Investigational Site
🇳🇱Nieuwegein, Netherlands
1237.5.45006 Boehringer Ingelheim Investigational Site
🇩🇰Odense C, Denmark
1237.5.02005 Boehringer Ingelheim Investigational Site
🇨🇦Burlington, Ontario, Canada
1237.5.81043 Boehringer Ingelheim Investigational Site
🇯🇵Yanagawa-shi, Fukuoka,, Japan
1237.5.49003 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.5.49012 Boehringer Ingelheim Investigational Site
🇩🇪Oschersleben, Germany
1237.5.01009 Boehringer Ingelheim Investigational Site
🇺🇸Oklahoma City, Oklahoma, United States
1237.5.01002 Boehringer Ingelheim Investigational Site
🇺🇸San Antonio, Texas, United States
1237.5.01019 Boehringer Ingelheim Investigational Site
🇺🇸Omaha, Nebraska, United States
1237.5.01006 Boehringer Ingelheim Investigational Site
🇺🇸Cincinnati, Ohio, United States
1237.5.01038 Boehringer Ingelheim Investigational Site
🇺🇸Jasper, Alabama, United States
1237.5.01034 Boehringer Ingelheim Investigational Site
🇺🇸Stamford, Connecticut, United States
1237.5.01010 Boehringer Ingelheim Investigational Site
🇺🇸Clearwater, Florida, United States
1237.5.01036 Boehringer Ingelheim Investigational Site
🇺🇸Mobile, Alabama, United States
1237.5.01024 Boehringer Ingelheim Investigational Site
🇺🇸Wheat Ridge, Colorado, United States
1237.5.01031 Boehringer Ingelheim Investigational Site
🇺🇸O'Fallon, Illinois, United States
1237.5.01003 Boehringer Ingelheim Investigational Site
🇺🇸Clearwater, Florida, United States
1237.5.01013 Boehringer Ingelheim Investigational Site
🇺🇸Livonia, Michigan, United States
1237.5.01025 Boehringer Ingelheim Investigational Site
🇺🇸Larchmont, New York, United States
1237.5.01016 Boehringer Ingelheim Investigational Site
🇺🇸Tabor City, North Carolina, United States
1237.5.01033 Boehringer Ingelheim Investigational Site
🇺🇸Tacoma, Washington, United States
1237.5.01007 Boehringer Ingelheim Investigational Site
🇺🇸Spokane, Washington, United States
1237.5.54010 Boehringer Ingelheim Investigational Site
🇦🇷Buenos Aires, Argentina
1237.5.54003 Boehringer Ingelheim Investigational Site
🇦🇷Capital Federal, Argentina
1237.5.54012 Boehringer Ingelheim Investigational Site
🇦🇷Monte Grande, Argentina
1237.5.54005 Boehringer Ingelheim Investigational Site
🇦🇷Rosario, Argentina
1237.5.54007 Boehringer Ingelheim Investigational Site
🇦🇷Mar del Plata, Argentina
1237.5.54009 Boehringer Ingelheim Investigational Site
🇦🇷Mendoza, Argentina
1237.5.54002 Boehringer Ingelheim Investigational Site
🇦🇷Cuidad Autonoma de Buenos Airess A, Argentina
1237.5.54004 Boehringer Ingelheim Investigational Site
🇦🇷San Miguel de Tucuma, Argentina
1237.5.54008 Boehringer Ingelheim Investigational Site
🇦🇷Quilmes, Argentina
1237.5.54011 Boehringer Ingelheim Investigational Site
🇦🇷San Miguel de Tucuman, Argentina
1237.5.61001 Boehringer Ingelheim Investigational Site
🇦🇺Toorak Gardens, South Australia, Australia
1237.5.35906 Boehringer Ingelheim Investigational Site
🇧🇬Shumen, Bulgaria
1237.5.61002 Boehringer Ingelheim Investigational Site
🇦🇺Woodville, South Australia, Australia
1237.5.35905 Boehringer Ingelheim Investigational Site
🇧🇬Plovdiv, Bulgaria
1237.5.35901 Boehringer Ingelheim Investigational Site
🇧🇬Rousse, Bulgaria
1237.5.61004 Boehringer Ingelheim Investigational Site
🇦🇺Frankston, Victoria, Australia
1237.5.35902 Boehringer Ingelheim Investigational Site
🇧🇬Sofia, Bulgaria
1237.5.35904 Boehringer Ingelheim Investigational Site
🇧🇬Sofia, Bulgaria
1237.5.35908 Boehringer Ingelheim Investigational Site
🇧🇬Veliko Tarnovo, Bulgaria
1237.5.02001 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1237.5.35903 Boehringer Ingelheim Investigational Site
🇧🇬Troyan, Bulgaria
1237.5.02002 Boehringer Ingelheim Investigational Site
🇨🇦Calgary, Alberta, Canada
1237.5.02004 Boehringer Ingelheim Investigational Site
🇨🇦Winnipeg, Manitoba, Canada
1237.5.02008 Boehringer Ingelheim Investigational Site
🇨🇦Sherbrooke, Quebec, Canada
1237.5.02007 Boehringer Ingelheim Investigational Site
🇨🇦Grimsby, Ontario, Canada
1237.5.02011 Boehringer Ingelheim Investigational Site
🇨🇦Ottawa, Ontario, Canada
1237.5.02009 Boehringer Ingelheim Investigational Site
🇨🇦Saskatoon, Saskatchewan, Canada
1237.5.86004 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
1237.5.02003 Boehringer Ingelheim Investigational Site
🇨🇦Quebec, Canada
1237.5.02006 Boehringer Ingelheim Investigational Site
🇨🇦Quebec, Canada
1237.5.86003 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
1237.5.86011 Boehringer Ingelheim Investigational Site
🇨🇳Changsha, China
1237.5.86014 Boehringer Ingelheim Investigational Site
🇨🇳Foshan, China
1237.5.86001 Boehringer Ingelheim Investigational Site
🇨🇳Guangzhou, China
1237.5.86015 Boehringer Ingelheim Investigational Site
🇨🇳Nan Ning, China
1237.5.86006 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1237.5.86007 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1237.5.86002 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1237.5.86005 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
1237.5.86010 Boehringer Ingelheim Investigational Site
🇨🇳Xi'An, China
1237.5.86008 Boehringer Ingelheim Investigational Site
🇨🇳Yangzhou, China
1237.5.42004 Boehringer Ingelheim Investigational Site
🇨🇿Beroun, Czech Republic
1237.5.86017 Boehringer Ingelheim Investigational Site
🇨🇳Yinchuan, China
1237.5.42002 Boehringer Ingelheim Investigational Site
🇨🇿Cvikov, Czech Republic
1237.5.42001 Boehringer Ingelheim Investigational Site
🇨🇿Praha 6, Czech Republic
1237.5.45002 Boehringer Ingelheim Investigational Site
🇩🇰Aalborg, Denmark
1237.5.42003 Boehringer Ingelheim Investigational Site
🇨🇿Znojmo, Czech Republic
1237.5.45001 Boehringer Ingelheim Investigational Site
🇩🇰København NV, Denmark
1237.5.45011 Boehringer Ingelheim Investigational Site
🇩🇰Næstved, Denmark
1237.5.45009 Boehringer Ingelheim Investigational Site
🇩🇰Hvidovre, Denmark
1237.5.45007 Boehringer Ingelheim Investigational Site
🇩🇰Kolding, Denmark
1237.5.45003 Boehringer Ingelheim Investigational Site
🇩🇰Silkeborg, Denmark
1237.5.45008 Boehringer Ingelheim Investigational Site
🇩🇰Roskilde, 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
🇪🇪Tallin, Estonia
1237.5.35804 Boehringer Ingelheim Investigational Site
🇫🇮Pori, Finland
1237.5.35801 Boehringer Ingelheim Investigational Site
🇫🇮Helsinki, Finland
1237.5.33007 Boehringer Ingelheim Investigational Site
🇫🇷Montpellier cedex 5, France
1237.5.33004 Boehringer Ingelheim Investigational Site
🇫🇷Bethune Cedex, France
1237.5.33008 Boehringer Ingelheim Investigational Site
🇫🇷Perpignan, France
1237.5.49002 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.5.49014 Boehringer Ingelheim Investigational Site
🇩🇪Neu-Isenburg, Germany
1237.5.49010 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1237.5.49004 Boehringer Ingelheim Investigational Site
🇩🇪Weinheim, Germany
1237.5.49008 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1237.5.50204 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, Guatemala
1237.5.50206 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala, 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
🇭🇺Kapuvar, Hungary
1237.5.91002 Boehringer Ingelheim Investigational Site
🇮🇳Bangalore, India
1237.5.91004 Boehringer Ingelheim Investigational Site
🇮🇳Coimbatore, India
1237.5.91007 Boehringer Ingelheim Investigational Site
🇮🇳Bangalore, 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
1237.5.91006 Boehringer Ingelheim Investigational Site
🇮🇳Pune, India
1237.5.39008 Boehringer Ingelheim Investigational Site
🇮🇹Cagliari, Italy
1237.5.39001 Boehringer Ingelheim Investigational Site
🇮🇹Pisa, Italy
1237.5.39002 Boehringer Ingelheim Investigational Site
🇮🇹Genova, Italy
1237.5.39009 Boehringer Ingelheim Investigational Site
🇮🇹Monza, Italy
1237.5.39004 Boehringer Ingelheim Investigational Site
🇮🇹Parma, Italy
1237.5.81001 Boehringer Ingelheim Investigational Site
🇯🇵Asahikawa, Hokkaido, Japan
1237.5.81003 Boehringer Ingelheim Investigational Site
🇯🇵Aoba-ku, Sendai, Miyagi, 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
1237.5.81037 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
1237.5.81005 Boehringer Ingelheim Investigational Site
🇯🇵Kamogawa, Chiba, Japan
1237.5.81021 Boehringer Ingelheim Investigational Site
🇯🇵Kagoshima, Kagoshima, Japan
1237.5.81042 Boehringer Ingelheim Investigational Site
🇯🇵Koga, Fukuoka, Japan
1237.5.81018 Boehringer Ingelheim Investigational Site
🇯🇵Kitakyusyu,Fukuoka, Japan
1237.5.81011 Boehringer Ingelheim Investigational Site
🇯🇵Kishiwada, Osaka, Japan
1237.5.81019 Boehringer Ingelheim Investigational Site
🇯🇵Koshi, Kumamoto, Japan
1237.5.81032 Boehringer Ingelheim Investigational Site
🇯🇵Komaki, Aichi, Japan
1237.5.81033 Boehringer Ingelheim Investigational Site
🇯🇵Komaki, Aichi, Japan
1237.5.81027 Boehringer Ingelheim Investigational Site
🇯🇵koto-ku, Tokyo, Japan
1237.5.81038 Boehringer Ingelheim Investigational Site
🇯🇵Kure, Hiroshima, Japan
1237.5.81015 Boehringer Ingelheim Investigational Site
🇯🇵Kurume, Fukuoka, Japan
1237.5.81030 Boehringer Ingelheim Investigational Site
🇯🇵Matsumoto, Nagano, Japan
1237.5.81036 Boehringer Ingelheim Investigational Site
🇯🇵Nagoya, Aichi, 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
1237.5.81004 Boehringer Ingelheim Investigational Site
🇯🇵Naka-gun, Ibaraki, Japan
1237.5.81022 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
1237.5.81007 Boehringer Ingelheim Investigational Site
🇯🇵Shinjyuku-ku, Tokyo, Japan
1237.5.81026 Boehringer Ingelheim Investigational Site
🇯🇵Shinagawa, Tokyo, Japan
1237.5.81013 Boehringer Ingelheim Investigational Site
🇯🇵Wakayama, Wakayama, Japan
1237.5.81039 Boehringer Ingelheim Investigational Site
🇯🇵Takamatsu, Kagawa, Japan
1237.5.81040 Boehringer Ingelheim Investigational Site
🇯🇵Takamatsu, Kagawa, Japan
1237.5.82001 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1237.5.82008 Boehringer Ingelheim Investigational Site
🇰🇷Daegu, Korea, Republic of
1237.5.81028 Boehringer Ingelheim Investigational Site
🇯🇵Yokohama, Kanagawa, Japan
1237.5.82003 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1237.5.82002 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1237.5.82005 Boehringer Ingelheim Investigational Site
🇰🇷Suwon, Korea, Republic of
1237.5.82007 Boehringer Ingelheim Investigational Site
🇰🇷Seoul, Korea, Republic of
1237.5.52002 Boehringer Ingelheim Investigational Site
🇲🇽Hermosillo, Mexico
1237.5.52007 Boehringer Ingelheim Investigational Site
🇲🇽Monterrey, Mexico
1237.5.82006 Boehringer Ingelheim Investigational Site
🇰🇷Wonju, Korea, Republic of
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
1237.5.31010 Boehringer Ingelheim Investigational Site
🇳🇱Hengelo, Netherlands
1237.5.31007 Boehringer Ingelheim Investigational Site
🇳🇱Heerlen, Netherlands
1237.5.31009 Boehringer Ingelheim Investigational Site
🇳🇱Hoorn, 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
1237.5.35101 Boehringer Ingelheim Investigational Site
🇵🇹Coimbra, Portugal
1237.5.35102 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1237.5.35105 Boehringer Ingelheim Investigational Site
🇵🇹Amadora, Portugal
1237.5.35104 Boehringer Ingelheim Investigational Site
🇵🇹Lisboa, Portugal
1237.5.35103 Boehringer Ingelheim Investigational Site
🇵🇹Porto, Portugal
1237.5.35107 Boehringer Ingelheim Investigational Site
🇵🇹Viseu, Portugal
1237.5.35106 Boehringer Ingelheim Investigational Site
🇵🇹Vila Nova de Gaia, Portugal
1237.5.07003 Boehringer Ingelheim Investigational Site
🇷🇺Kazan, Russian Federation
1237.5.07005 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
1237.5.07001 Boehringer Ingelheim Investigational Site
🇷🇺Gatchina (Leningradskaya oblast), Russian Federation
1237.5.07004 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
1237.5.38602 Boehringer Ingelheim Investigational Site
🇸🇮Golnik, Slovenia
1237.5.38601 Boehringer Ingelheim Investigational Site
🇸🇮Golnik, Slovenia
1237.5.90003 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
1237.5.07002 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
1237.5.90004 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
1237.5.90002 Boehringer Ingelheim Investigational Site
🇹🇷Izmir, Turkey
1237.5.90005 Boehringer Ingelheim Investigational Site
🇹🇷Izmit, Turkey
1237.5.90001 Boehringer Ingelheim Investigational Site
🇹🇷Mersin, Turkey
1237.5.01008 Boehringer Ingelheim Investigational Site
🇺🇸Rochester, New York, United States
1237.5.01039 Boehringer Ingelheim Investigational Site
🇺🇸Dayton, Ohio, United States
1237.5.01017 Boehringer Ingelheim Investigational Site
🇺🇸Biddeford, Maine, United States