MedPath

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

Phase 3
Completed
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
Registration Number
NCT01431287
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 COPD.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2539
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
tiotropium high doseRespimatOnce daily 2 puffs solution for inhalation Respimat
tiotropium+olodaterol low dose FDCtiotropium + olodaterolOnce daily 2 puffs solution for inhalation Respimat
tiotropium low doseRespimatOnce daily 2 puffs solution for inhalation Respimat
tiotropium+olodaterol high dose FDCtiotropium + olodaterolOnce daily 2 puffs solution for inhalation Respimat
tiotropium+olodaterol high dose FDCRespimatOnce daily 2 puffs solution for inhalation Respimat
tiotropium+olodaterol low dose FDCRespimatOnce daily 2 puffs solution for inhalation Respimat
olodaterololodaterolOnce daily 2 puffs solution for inhalation Respimat
olodaterolRespimatOnce daily 2 puffs solution for inhalation Respimat
tiotropium low dosetiotropiumOnce daily 2 puffs solution for inhalation Respimat
tiotropium high dosetiotropiumOnce daily 2 puffs solution for inhalation Respimat
Primary Outcome Measures
NameTimeMethod
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 1691 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 1701 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 1237.6 (NCT01431287) and 1237.5 (NCT01431274).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
NameTimeMethod
FEV1 AUC(0-3h) Response on Day 11 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 3651 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.

Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 11 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.

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

Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) is the key secondary endpoint.

The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

FEV1 AUC(0-3h) Response on Day 851 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.

Trough FEV1 Response on Day 1691 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 169

Trough FEV1 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 FVC Response on Day 151 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 431 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 FEV1 Response on Day 151 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 431 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 851 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 85

Trough FEV1 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 3651 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.

Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 851 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.

Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 1691 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(0-12h) Response in Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)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.

Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 3651 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 851 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 1701 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23h and at 23h 50 min after inhalation of study medication on day 170

Trough FVC 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 3651 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.

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

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

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

Mahler TDI focal score on Day 85 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)Day 43

Mahler TDI focal score on Day 43 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

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

Mahler TDI focal score on Day 365 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.

Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.

Trial Locations

Locations (240)

1237.6.42106 Boehringer Ingelheim Investigational Site

🇸🇰

Zilina, Slovakia

1237.6.27002 Boehringer Ingelheim Investigational Site

🇿🇦

Bellville, South Africa

1237.6.01129 Boehringer Ingelheim Investigational Site

🇺🇸

Henderson, Nevada, United States

1237.6.01101 Boehringer Ingelheim Investigational Site

🇺🇸

Philadelphia, Pennsylvania, United States

1237.6.02105 Boehringer Ingelheim Investigational Site

🇨🇦

Sherbrooke, Quebec, Canada

1237.6.02106 Boehringer Ingelheim Investigational Site

🇨🇦

Moncton, New Brunswick, Canada

1237.6.01114 Boehringer Ingelheim Investigational Site

🇺🇸

Cincinnati, Ohio, United States

1237.6.86114 Boehringer Ingelheim Investigational Site

🇨🇳

Jinan, China

1237.6.86102 Boehringer Ingelheim Investigational Site

🇨🇳

Beijing, China

1237.6.81108 Boehringer Ingelheim Investigational Site

🇯🇵

Kashiwa, Chiba, Japan

1237.6.02109 Boehringer Ingelheim Investigational Site

🇨🇦

Edmonton, Alberta, Canada

1237.6.43003 Boehringer Ingelheim Investigational Site

🇦🇹

Salzburg, Austria

1237.6.81135 Boehringer Ingelheim Investigational Site

🇯🇵

Kita-ku, Okayama, Okayama, Japan

1237.6.02111 Boehringer Ingelheim Investigational Site

🇨🇦

Vancouver, British Columbia, Canada

1237.6.43002 Boehringer Ingelheim Investigational Site

🇦🇹

Innsbruck, Austria

1237.6.32005 Boehringer Ingelheim Investigational Site

🇧🇪

Bruxelles, Belgium

1237.6.32001 Boehringer Ingelheim Investigational Site

🇧🇪

Leuven, Belgium

1237.6.32010 Boehringer Ingelheim Investigational Site

🇧🇪

Turnhout, Belgium

1237.6.57003 Boehringer Ingelheim Investigational Site

🇨🇴

Bogota DC, Colombia

1237.6.01105 Boehringer Ingelheim Investigational Site

🇺🇸

Union, South Carolina, United States

1237.6.38502 Boehringer Ingelheim Investigational Site

🇭🇷

Zadar, Croatia

1237.6.57004 Boehringer Ingelheim Investigational Site

🇨🇴

Floridablanca, Colombia

1237.6.81131 Boehringer Ingelheim Investigational Site

🇯🇵

Nishi-ku, Kobe, Hyogo, Japan

1237.6.81143 Boehringer Ingelheim Investigational Site

🇯🇵

Tomigusuku, Okinawa, Japan

1237.6.40002 Boehringer Ingelheim Investigational Site

🇷🇴

Bucuresti, Romania

1237.6.81141 Boehringer Ingelheim Investigational Site

🇯🇵

Okinawa, Okinawa, Japan

1237.6.81105 Boehringer Ingelheim Investigational Site

🇯🇵

Mito, Ibaraki, Japan

1237.6.81140 Boehringer Ingelheim Investigational Site

🇯🇵

Shimajiri-gun, Okinawa, Japan

1237.6.81130 Boehringer Ingelheim Investigational Site

🇯🇵

Yabu, Hyogo, Japan

1237.6.81113 Boehringer Ingelheim Investigational Site

🇯🇵

Kanazawa, Yokohama, Kanagawa, Japan

1237.6.81136 Boehringer Ingelheim Investigational Site

🇯🇵

Kurashiki, Okayama, Japan

1237.6.81107 Boehringer Ingelheim Investigational Site

🇯🇵

Soka, Saitama, Japan

1237.6.47005 Boehringer Ingelheim Investigational Site

🇳🇴

Elverum, Norway

1237.6.42101 Boehringer Ingelheim Investigational Site

🇸🇰

Bardejov, Slovakia

1237.6.07004 Boehringer Ingelheim Investigational Site

🇷🇺

Moscow, Russian Federation

1237.6.81111 Boehringer Ingelheim Investigational Site

🇯🇵

Shinjuku-ku, Tokyo, Japan

1237.6.81145 Boehringer Ingelheim Investigational Site

🇯🇵

Shinjuku-ku, Tokyo, Japan

1237.6.38105 Boehringer Ingelheim Investigational Site

🇷🇸

Belgrade, Serbia

1237.6.40003 Boehringer Ingelheim Investigational Site

🇷🇴

Cluj, Romania

1237.6.07003 Boehringer Ingelheim Investigational Site

🇷🇺

St. Petersburg, Russian Federation

1237.6.47002 Boehringer Ingelheim Investigational Site

🇳🇴

Kløfta, Norway

1237.6.47001 Boehringer Ingelheim Investigational Site

🇳🇴

Hønefoss, Norway

1237.6.38102 Boehringer Ingelheim Investigational Site

🇷🇸

Kragujevac, Serbia

1237.6.38103 Boehringer Ingelheim Investigational Site

🇷🇸

Belgrade, Serbia

1237.6.38101 Boehringer Ingelheim Investigational Site

🇷🇸

Nis, Serbia

1237.6.01115 Boehringer Ingelheim Investigational Site

🇺🇸

Oklahoma City, Oklahoma, United States

1237.6.44010 Boehringer Ingelheim Investigational Site

🇬🇧

Chertsey, United Kingdom

1237.6.34008 Boehringer Ingelheim Investigational Site

🇪🇸

Badalona (Barcelona), Spain

1237.6.88602 Boehringer Ingelheim Investigational Site

🇨🇳

New Taipei City, Taiwan

1237.6.88604 Boehringer Ingelheim Investigational Site

🇨🇳

Taichung, Taiwan

1237.6.90105 Boehringer Ingelheim Investigational Site

🇹🇷

Ankara, Turkey

1237.6.46003 Boehringer Ingelheim Investigational Site

🇸🇪

Boden, Sweden

1237.6.44001 Boehringer Ingelheim Investigational Site

🇬🇧

Manchester, United Kingdom

1237.6.88607 Boehringer Ingelheim Investigational Site

🇨🇳

Kaohsiung City, Taiwan

1237.6.88608 Boehringer Ingelheim Investigational Site

🇨🇳

Kaohsiung, Taiwan

1237.6.88605 Boehringer Ingelheim Investigational Site

🇨🇳

Tainan, Taiwan

1237.6.46004 Boehringer Ingelheim Investigational Site

🇸🇪

Stockholm, Sweden

1237.6.90101 Boehringer Ingelheim Investigational Site

🇹🇷

Izmir, Turkey

1237.6.88601 Boehringer Ingelheim Investigational Site

🇨🇳

Taipei, Taiwan

1237.6.34004 Boehringer Ingelheim Investigational Site

🇪🇸

San Juan de Alicante, Spain

1237.6.88603 Boehringer Ingelheim Investigational Site

🇨🇳

Taoyuan County, Taiwan

1237.6.46001 Boehringer Ingelheim Investigational Site

🇸🇪

Lund, Sweden

1237.6.44009 Boehringer Ingelheim Investigational Site

🇬🇧

Blackpool, United Kingdom

1237.6.90103 Boehringer Ingelheim Investigational Site

🇹🇷

Denizli, Turkey

1237.6.34003 Boehringer Ingelheim Investigational Site

🇪🇸

Barcelona, Spain

1237.6.27005 Boehringer Ingelheim Investigational Site

🇿🇦

Pretoria, South Africa

1237.6.34009 Boehringer Ingelheim Investigational Site

🇪🇸

Barcelona, Spain

1237.6.90102 Boehringer Ingelheim Investigational Site

🇹🇷

Izmir, Turkey

1237.6.46002 Boehringer Ingelheim Investigational Site

🇸🇪

Göteborg, Sweden

1237.6.46006 Boehringer Ingelheim Investigational Site

🇸🇪

Härnösand, Sweden

1237.6.46005 Boehringer Ingelheim Investigational Site

🇸🇪

Höllviken, Sweden

1237.6.46007 Boehringer Ingelheim Investigational Site

🇸🇪

Uddevalla, Sweden

1237.6.44002 Boehringer Ingelheim Investigational Site

🇬🇧

Blackpool, United Kingdom

1237.6.44007 Boehringer Ingelheim Investigational Site

🇬🇧

Bristol, United Kingdom

1237.6.44011 Boehringer Ingelheim Investigational Site

🇬🇧

Fleetwood, United Kingdom

1237.6.44008 Boehringer Ingelheim Investigational Site

🇬🇧

Midsomer Norton, United Kingdom

1237.6.90104 Boehringer Ingelheim Investigational Site

🇹🇷

Istanbul, Turkey

1237.6.49028 Boehringer Ingelheim Investigational Site

🇩🇪

Mainz, Germany

1237.6.01120 Boehringer Ingelheim Investigational Site

🇺🇸

Fort Collins, Colorado, United States

1237.6.01106 Boehringer Ingelheim Investigational Site

🇺🇸

Greer, California, United States

1237.6.01131 Boehringer Ingelheim Investigational Site

🇺🇸

Danbury, Connecticut, United States

1237.6.01117 Boehringer Ingelheim Investigational Site

🇺🇸

Waterbury, Connecticut, United States

1237.6.01118 Boehringer Ingelheim Investigational Site

🇺🇸

Deland, Florida, United States

1237.6.01126 Boehringer Ingelheim Investigational Site

🇺🇸

Tampa, Florida, United States

1237.6.01109 Boehringer Ingelheim Investigational Site

🇺🇸

Winter Park, Florida, United States

1237.6.01134 Boehringer Ingelheim Investigational Site

🇺🇸

Atlanta, Georgia, United States

1237.6.01107 Boehringer Ingelheim Investigational Site

🇺🇸

Couer d'Alene, Idaho, United States

1237.6.01128 Boehringer Ingelheim Investigational Site

🇺🇸

Baltimore, Maryland, United States

1237.6.01130 Boehringer Ingelheim Investigational Site

🇺🇸

North Dartmouth, Massachusetts, United States

1237.6.01116 Boehringer Ingelheim Investigational Site

🇺🇸

Plymouth, Minnesota, United States

1237.6.01121 Boehringer Ingelheim Investigational Site

🇺🇸

St. Louis, Missouri, United States

1237.6.01123 Boehringer Ingelheim Investigational Site

🇺🇸

St. Louis, Missouri, United States

1237.6.01136 Boehringer Ingelheim Investigational Site

🇺🇸

Marlton, New Jersey, United States

1237.6.01108 Boehringer Ingelheim Investigational Site

🇺🇸

Albuquerque, New Mexico, United States

1237.6.01127 Boehringer Ingelheim Investigational Site

🇺🇸

Bayside, New York, United States

1237.6.01139 Boehringer Ingelheim Investigational Site

🇺🇸

Great Neck, New York, United States

1237.6.01102 Boehringer Ingelheim Investigational Site

🇺🇸

Columbus, Ohio, United States

1237.6.01113 Boehringer Ingelheim Investigational Site

🇺🇸

East Providence, Rhode Island, United States

1237.6.01122 Boehringer Ingelheim Investigational Site

🇺🇸

Charleston, South Carolina, United States

1237.6.34001 Boehringer Ingelheim Investigational Site

🇪🇸

Hospitalet de Llobregat, Spain

1237.6.34002 Boehringer Ingelheim Investigational Site

🇪🇸

Mérida, Spain

1237.6.34005 Boehringer Ingelheim Investigational Site

🇪🇸

Pozuelo de Alarcón, Spain

1237.6.01132 Boehringer Ingelheim Investigational Site

🇺🇸

Greenville, South Carolina, United States

1237.6.34006 Boehringer Ingelheim Investigational Site

🇪🇸

Vic (Barcelona), Spain

1237.6.01137 Boehringer Ingelheim Investigational Site

🇺🇸

Greenville, South Carolina, United States

1237.6.01111 Boehringer Ingelheim Investigational Site

🇺🇸

Spartanburg, South Carolina, United States

1237.6.01138 Boehringer Ingelheim Investigational Site

🇺🇸

Killeen, Texas, United States

1237.6.01124 Boehringer Ingelheim Investigational Site

🇺🇸

McKinney, Texas, United States

1237.6.01112 Boehringer Ingelheim Investigational Site

🇺🇸

Richmond, Virginia, United States

1237.6.01133 Boehringer Ingelheim Investigational Site

🇺🇸

Richmond, Virginia, United States

1237.6.01125 Boehringer Ingelheim Investigational Site

🇺🇸

Spokane, Washington, United States

1237.6.01103 Boehringer Ingelheim Investigational Site

🇺🇸

Tacoma, Washington, United States

1237.6.43006 Boehringer Ingelheim Investigational Site

🇦🇹

Feldbach, Austria

1237.6.43005 Boehringer Ingelheim Investigational Site

🇦🇹

Gänserndorf, Austria

1237.6.43004 Boehringer Ingelheim Investigational Site

🇦🇹

Leoben, Austria

1237.6.43001 Boehringer Ingelheim Investigational Site

🇦🇹

Linz, Austria

1237.6.32007 Boehringer Ingelheim Investigational Site

🇧🇪

Brussel, Belgium

1237.6.32004 Boehringer Ingelheim Investigational Site

🇧🇪

Gent, Belgium

1237.6.32002 Boehringer Ingelheim Investigational Site

🇧🇪

Jambes, Belgium

1237.6.32009 Boehringer Ingelheim Investigational Site

🇧🇪

Lebbeke, Belgium

1237.6.86115 Boehringer Ingelheim Investigational Site

🇨🇳

Changsha, China

1237.6.32006 Boehringer Ingelheim Investigational Site

🇧🇪

Liège, Belgium

1237.6.32008 Boehringer Ingelheim Investigational Site

🇧🇪

Oostende, Belgium

1237.6.55013 Boehringer Ingelheim Investigational Site

🇧🇷

Botucatu, Brazil

1237.6.55010 Boehringer Ingelheim Investigational Site

🇧🇷

Florianopolis, Brazil

1237.6.55012 Boehringer Ingelheim Investigational Site

🇧🇷

Passo Fundo, Brazil

1237.6.55001 Boehringer Ingelheim Investigational Site

🇧🇷

Porto Alegre, Brazil

1237.6.55003 Boehringer Ingelheim Investigational Site

🇧🇷

Porto Alegre, Brazil

1237.6.55002 Boehringer Ingelheim Investigational Site

🇧🇷

Porto Alegre, Brazil

1237.6.55005 Boehringer Ingelheim Investigational Site

🇧🇷

Porto Alegre, Brazil

1237.6.55009 Boehringer Ingelheim Investigational Site

🇧🇷

Porto Alegre, Brazil

1237.6.55006 Boehringer Ingelheim Investigational Site

🇧🇷

Sao Paulo, Brazil

1237.6.55007 Boehringer Ingelheim Investigational Site

🇧🇷

Sao Paulo, Brazil

1237.6.55011 Boehringer Ingelheim Investigational Site

🇧🇷

Sao Paulo, Brazil

1237.6.02110 Boehringer Ingelheim Investigational Site

🇨🇦

Courtice, Ontario, Canada

1237.6.02101 Boehringer Ingelheim Investigational Site

🇨🇦

Downsview, Ontario, Canada

1237.6.02112 Boehringer Ingelheim Investigational Site

🇨🇦

Sarnia, Ontario, Canada

1237.6.02103 Boehringer Ingelheim Investigational Site

🇨🇦

Toronto, Ontario, Canada

1237.6.02102 Boehringer Ingelheim Investigational Site

🇨🇦

Windsor, Ontario, Canada

1237.6.02104 Boehringer Ingelheim Investigational Site

🇨🇦

Point Claire, Quebec, Canada

1237.6.01104 Boehringer Ingelheim Investigational Site

🇺🇸

Minneapolis, Minnesota, United States

1237.6.02108 Boehringer Ingelheim Investigational Site

🇨🇦

Ste-Foy, Quebec, Canada

1237.6.86117 Boehringer Ingelheim Investigational Site

🇨🇳

Baotou, China

1237.6.86104 Boehringer Ingelheim Investigational Site

🇨🇳

Beijing, China

1237.6.86105 Boehringer Ingelheim Investigational Site

🇨🇳

Beijing, China

1237.6.86110 Boehringer Ingelheim Investigational Site

🇨🇳

Chengdu, China

1237.6.86111 Boehringer Ingelheim Investigational Site

🇨🇳

Chongqing, China

1237.6.49021 Boehringer Ingelheim Investigational Site

🇩🇪

Hannover, Germany

1237.6.86109 Boehringer Ingelheim Investigational Site

🇨🇳

Haikou, China

1237.6.86108 Boehringer Ingelheim Investigational Site

🇨🇳

Hangzhou, China

1237.6.86116 Boehringer Ingelheim Investigational Site

🇨🇳

Hohhot, China

1237.6.86106 Boehringer Ingelheim Investigational Site

🇨🇳

Nanjing, China

1237.6.42102 Boehringer Ingelheim Investigational Site

🇸🇰

Bojnice, Slovakia

1237.6.86101 Boehringer Ingelheim Investigational Site

🇨🇳

Shanghai, China

1237.6.86113 Boehringer Ingelheim Investigational Site

🇨🇳

Shenyang, China

1237.6.86107 Boehringer Ingelheim Investigational Site

🇨🇳

Suzhou, China

1237.6.86112 Boehringer Ingelheim Investigational Site

🇨🇳

Xi'An, China

1237.6.57001 Boehringer Ingelheim Investigational Site

🇨🇴

Bogota DC, Colombia

1237.6.57007 Boehringer Ingelheim Investigational Site

🇨🇴

Bogota DC, Colombia

1237.6.57008 Boehringer Ingelheim Investigational Site

🇨🇴

Bogota, Colombia

1237.6.57006 Boehringer Ingelheim Investigational Site

🇨🇴

Cali, Colombia

1237.6.38503 Boehringer Ingelheim Investigational Site

🇭🇷

Petrinja, Croatia

1237.6.38504 Boehringer Ingelheim Investigational Site

🇭🇷

Rijeka, Croatia

1237.6.38501 Boehringer Ingelheim Investigational Site

🇭🇷

Zagreb, Croatia

1237.6.49022 Boehringer Ingelheim Investigational Site

🇩🇪

Aschaffenburg, Germany

1237.6.49027 Boehringer Ingelheim Investigational Site

🇩🇪

Frankfurt, Germany

1237.6.49017 Boehringer Ingelheim Investigational Site

🇩🇪

Berlin, Germany

1237.6.49026 Boehringer Ingelheim Investigational Site

🇩🇪

Frankfurt, Germany

1237.6.49025 Boehringer Ingelheim Investigational Site

🇩🇪

Großhansdorf, Germany

1237.6.49016 Boehringer Ingelheim Investigational Site

🇩🇪

Halle, Germany

1237.6.49024 Boehringer Ingelheim Investigational Site

🇩🇪

Hamburg, Germany

1237.6.49019 Boehringer Ingelheim Investigational Site

🇩🇪

Leipzig, Germany

1237.6.49018 Boehringer Ingelheim Investigational Site

🇩🇪

Rodgau/Dudenhofen, Germany

1237.6.49020 Boehringer Ingelheim Investigational Site

🇩🇪

Schwerin, Germany

1237.6.49023 Boehringer Ingelheim Investigational Site

🇩🇪

Teuchern, Germany

1237.6.36001 Boehringer Ingelheim Investigational Site

🇭🇺

Debrecen, Hungary

1237.6.36005 Boehringer Ingelheim Investigational Site

🇭🇺

Pecs, Hungary

1237.6.36004 Boehringer Ingelheim Investigational Site

🇭🇺

Gödöllö, Hungary

1237.6.36003 Boehringer Ingelheim Investigational Site

🇭🇺

Sopron, Hungary

1237.6.91011 Boehringer Ingelheim Investigational Site

🇮🇳

Coimbatore, India

1237.6.36002 Boehringer Ingelheim Investigational Site

🇭🇺

Szeged, Hungary

1237.6.91004 Boehringer Ingelheim Investigational Site

🇮🇳

Jaipur, India

1237.6.91003 Boehringer Ingelheim Investigational Site

🇮🇳

Chennai, India

1237.6.91002 Boehringer Ingelheim Investigational Site

🇮🇳

Kolkatta, India

1237.6.91007 Boehringer Ingelheim Investigational Site

🇮🇳

Maharastra, India

1237.6.91006 Boehringer Ingelheim Investigational Site

🇮🇳

Mumbai, India

1237.6.91009 Boehringer Ingelheim Investigational Site

🇮🇳

Nashik, Maharashtra, India

1237.6.91008 Boehringer Ingelheim Investigational Site

🇮🇳

Pune, India

1237.6.35304 Boehringer Ingelheim Investigational Site

🇮🇪

County Limerick, Ireland

1237.6.35303 Boehringer Ingelheim Investigational Site

🇮🇪

Dublin 24, Ireland

1237.6.35301 Boehringer Ingelheim Investigational Site

🇮🇪

Dublin 4, Ireland

1237.6.81123 Boehringer Ingelheim Investigational Site

🇯🇵

Aoi-ku, Shizuoka, Shizuoka, Japan

1237.6.81127 Boehringer Ingelheim Investigational Site

🇯🇵

Abeno-ku, Osaka, Osaka, Japan

1237.6.81132 Boehringer Ingelheim Investigational Site

🇯🇵

Chuo-ku, Kobe, Hyogo, Japan

1237.6.81137 Boehringer Ingelheim Investigational Site

🇯🇵

Fukuyama, Hiroshima, Japan

1237.6.81109 Boehringer Ingelheim Investigational Site

🇯🇵

Hachioji, Tokyo, Japan

1237.6.42103 Boehringer Ingelheim Investigational Site

🇸🇰

Spisska Nova Ves, Slovakia

1237.6.81121 Boehringer Ingelheim Investigational Site

🇯🇵

Fukui, Fukui, Japan

1237.6.81134 Boehringer Ingelheim Investigational Site

🇯🇵

Himeji, Hyogo, Japan

1237.6.81139 Boehringer Ingelheim Investigational Site

🇯🇵

Iizuka, Fukuoka, Japan

1237.6.81106 Boehringer Ingelheim Investigational Site

🇯🇵

Hitachi, Ibaraki, Japan

1237.6.81102 Boehringer Ingelheim Investigational Site

🇯🇵

Iwamizawa, Hokkaido, Japan

1237.6.81117 Boehringer Ingelheim Investigational Site

🇯🇵

Kamakura, Kanagawa, Japan

1237.6.81120 Boehringer Ingelheim Investigational Site

🇯🇵

Kanazawa, Ishikawa, Japan

1237.6.81114 Boehringer Ingelheim Investigational Site

🇯🇵

Kawasaki-ku, Kawasaki, Kanagawa, Japan

1237.6.81126 Boehringer Ingelheim Investigational Site

🇯🇵

Kita-ku, Sakai, Osaka, Japan

1237.6.81101 Boehringer Ingelheim Investigational Site

🇯🇵

Kita-ku, Sapporo, Hokkaido, Japan

1237.6.81116 Boehringer Ingelheim Investigational Site

🇯🇵

Minami-ku, Yokohama, Kanagawa, Japan

1237.6.81112 Boehringer Ingelheim Investigational Site

🇯🇵

Mitaka, Tokyo, Japan

1237.6.81118 Boehringer Ingelheim Investigational Site

🇯🇵

Minami-ku, Yokohama, Kanagawa, Japan

1237.6.81142 Boehringer Ingelheim Investigational Site

🇯🇵

Naha, Okinawa, Japan

1237.6.81104 Boehringer Ingelheim Investigational Site

🇯🇵

Obihiro, Hokkaido, Japan

1237.6.81110 Boehringer Ingelheim Investigational Site

🇯🇵

Ota-ku, Tokyo, Japan

1237.6.81138 Boehringer Ingelheim Investigational Site

🇯🇵

Sakaide, Kagawa, Japan

1237.6.81103 Boehringer Ingelheim Investigational Site

🇯🇵

Sapporo, Hokkaido, Japan

1237.6.81144 Boehringer Ingelheim Investigational Site

🇯🇵

Shimajiri-gun, Okinawa, Japan

1237.6.81133 Boehringer Ingelheim Investigational Site

🇯🇵

Takarazuka, Hyogo, Japan

1237.6.81122 Boehringer Ingelheim Investigational Site

🇯🇵

Takayama, Gifu, Japan

1237.6.81128 Boehringer Ingelheim Investigational Site

🇯🇵

Toyonaka, Osaka, Japan

1237.6.81124 Boehringer Ingelheim Investigational Site

🇯🇵

Uji, Kyoto, Japan

1237.6.81129 Boehringer Ingelheim Investigational Site

🇯🇵

Yao, Osaka, Japan

1237.6.81119 Boehringer Ingelheim Investigational Site

🇯🇵

Yokosuka, Kanagawa, Japan

1237.6.47004 Boehringer Ingelheim Investigational Site

🇳🇴

Lierskogen, Norway

1237.6.47003 Boehringer Ingelheim Investigational Site

🇳🇴

Oslo, Norway

1237.6.47008 Boehringer Ingelheim Investigational Site

🇳🇴

Svelvik, Norway

1237.6.47007 Boehringer Ingelheim Investigational Site

🇳🇴

SKI, Norway

1237.6.40004 Boehringer Ingelheim Investigational Site

🇷🇴

Arad, Romania

1237.6.40005 Boehringer Ingelheim Investigational Site

🇷🇴

Arad, Romania

1237.6.40001 Boehringer Ingelheim Investigational Site

🇷🇴

Bucharest, Romania

1237.6.07005 Boehringer Ingelheim Investigational Site

🇷🇺

Moscow, Russian Federation

1237.6.07002 Boehringer Ingelheim Investigational Site

🇷🇺

St. Petersburg, Russian Federation

1237.6.07001 Boehringer Ingelheim Investigational Site

🇷🇺

Yaroslavl, Russian Federation

1237.6.38104 Boehringer Ingelheim Investigational Site

🇷🇸

Belgrade, Serbia

1237.6.01135 Boehringer Ingelheim Investigational Site

🇺🇸

Charlotte, North Carolina, United States

1237.6.42104 Boehringer Ingelheim Investigational Site

🇸🇰

Kosice, Slovakia

1237.6.42107 Boehringer Ingelheim Investigational Site

🇸🇰

Nitra, Slovakia

1237.6.27003 Boehringer Ingelheim Investigational Site

🇿🇦

Cape Town, South Africa

1237.6.27001 Boehringer Ingelheim Investigational Site

🇿🇦

Cape Town, South Africa

1237.6.27004 Boehringer Ingelheim Investigational Site

🇿🇦

Cape Town, South Africa

1237.6.01110 Boehringer Ingelheim Investigational Site

🇺🇸

Lafayette, Louisiana, United States

© Copyright 2025. All Rights Reserved by MedPath