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Tiotropium+Olodaterol Fixed Dose Combination (FDC) in Chronic Obstructive Pulmonary Disease (OTEMTO 2)

Phase 3
Completed
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
Registration Number
NCT02006732
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The objective of this study is to assess the efficacy and safety of 12 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the Respimat inhaler) compared with tiotropium and placebo in patients with COPD.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
809
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
tiotropiumtiotropiumOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol low dosetiotropiumOnce daily 2 puffs solution for inhalation Respimat
placeboplaceboOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol low doseolodaterolOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol high doseolodaterolOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol high dosetiotropiumOnce daily 2 puffs solution for inhalation Respimat
Primary Outcome Measures
NameTimeMethod
FEV1 AUC0-3h Responsebaseline and 12 weeks

Forced expiratory volume in one second (FEV1) Area under the curve (AUC) 0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in litres. FEV1 AUC0-3h response was defined as FEV1 AUC0-3h minus baseline FEV1. The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Trough FEV1 Response (Change From Baseline)baseline and 12 weeks

Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FEV1 measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FEV1 response was defines as trough FEV1 minus baseline FEV1. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Data From This Individual Study12 weeks treatment

The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life).

The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Combined Dataset From This Study and the Replicate Study NCT0196435212 weeks treatment

This endpoint was evaluated after combining the data from this and the replicate study NCT01964352 as specified in the analysis plan. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life).

The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Secondary Outcome Measures
NameTimeMethod
TDI Focal Score Based on Data From This Individual Study12 weeks

Mahler Transitional Dyspnoea Index (TDI) focal score was performed to measure the effect of the treatment on patients' dyspnoea.(Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9).

The adjusted mean (SE) are obtained from fitting an MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

FVC AUC0-3h Response (Change From Baseline)baseline and 12 weeks

The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Trough Forced Vital Capacity (FVC) Response (Change From Baseline)baseline and 12 weeks

Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FVC measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FVC response was defined as trough FVC minus baseline FVC. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

TDI Focal Score Based on Combined Dataset From This Study and the Replicate Study NCT0196435212 weeks

This endpoint was evaluated after combining the data from this and the replicate study NCT01964352 as specified in the analysis plan. Mahler Transitional Dyspnoea Index (TDI) focal score was performed to measure the effect of the treatment on patients' dyspnoea.(Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9).

The adjusted mean (SE) are obtained from fitting an MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Trial Locations

Locations (78)

1237.26.10620 Boehringer Ingelheim Investigational Site

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Jasper, Alabama, United States

1237.26.10618 Boehringer Ingelheim Investigational Site

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Stamford, Connecticut, United States

1237.26.10619 Boehringer Ingelheim Investigational Site

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Clearwater, Florida, United States

1237.26.10614 Boehringer Ingelheim Investigational Site

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Tampa, Florida, United States

1237.26.10616 Boehringer Ingelheim Investigational Site

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Duluth, Georgia, United States

1237.26.10613 Boehringer Ingelheim Investigational Site

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St. Louis, Missouri, United States

1237.26.10615 Boehringer Ingelheim Investigational Site

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Greensboro, North Carolina, United States

1237.26.10603 Boehringer Ingelheim Investigational Site

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Columbus, Ohio, United States

1237.26.10621 Boehringer Ingelheim Investigational Site

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Dayton, Ohio, United States

1237.26.10612 Boehringer Ingelheim Investigational Site

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Toledo, Ohio, United States

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1237.26.10620 Boehringer Ingelheim Investigational Site
🇺🇸Jasper, Alabama, United States
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