Tiotropium+Olodaterol Fixed Dose Combination (FDC) in Chronic Obstructive Pulmonary Disease (OTEMTO 2)
- 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
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tiotropium tiotropium Once daily 2 puffs solution for inhalation Respimat tiotropium + olodaterol low dose tiotropium Once daily 2 puffs solution for inhalation Respimat placebo placebo Once daily 2 puffs solution for inhalation Respimat tiotropium + olodaterol low dose olodaterol Once daily 2 puffs solution for inhalation Respimat tiotropium + olodaterol high dose olodaterol Once daily 2 puffs solution for inhalation Respimat tiotropium + olodaterol high dose tiotropium Once daily 2 puffs solution for inhalation Respimat
- Primary Outcome Measures
Name Time Method FEV1 AUC0-3h Response baseline 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 Study 12 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 NCT01964352 12 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
Name Time Method TDI Focal Score Based on Data From This Individual Study 12 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 NCT01964352 12 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)
1237.26.10613 Boehringer Ingelheim Investigational Site
🇺🇸St. Louis, Missouri, United States
1237.26.10606 Boehringer Ingelheim Investigational Site
🇺🇸Medford, Oregon, United States
1237.26.61004 Boehringer Ingelheim Investigational Site
🇦🇺Concord, New South Wales, Australia
1237.26.10620 Boehringer Ingelheim Investigational Site
🇺🇸Jasper, Alabama, United States
1237.26.10612 Boehringer Ingelheim Investigational Site
🇺🇸Toledo, Ohio, United States
1237.26.10621 Boehringer Ingelheim Investigational Site
🇺🇸Dayton, Ohio, United States
1237.26.27601 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
1237.26.10615 Boehringer Ingelheim Investigational Site
🇺🇸Greensboro, North Carolina, United States
1237.26.10610 Boehringer Ingelheim Investigational Site
🇺🇸East Providence, Rhode Island, United States
1237.26.27602 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
1237.26.46002 Boehringer Ingelheim Investigational Site
🇸🇪Stockholm, Sweden
1237.26.27604 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
1237.26.47001 Boehringer Ingelheim Investigational Site
🇳🇴Hønefoss, Norway
1237.26.47002 Boehringer Ingelheim Investigational Site
🇳🇴Kløfta, Norway
1237.26.27605 Boehringer Ingelheim Investigational Site
🇿🇦Durban, South Africa
1237.26.46001 Boehringer Ingelheim Investigational Site
🇸🇪Lund, Sweden
1237.26.46003 Boehringer Ingelheim Investigational Site
🇸🇪Uddevalla, Sweden
1237.26.46004 Boehringer Ingelheim Investigational Site
🇸🇪Höllviken, Sweden
1237.26.10609 Boehringer Ingelheim Investigational Site
🇺🇸Boerne, Texas, United States
1237.26.61005 Boehringer Ingelheim Investigational Site
🇦🇺Murdoch, Western Australia, Australia
1237.26.10605 Boehringer Ingelheim Investigational Site
🇺🇸Oklahoma City, Oklahoma, United States
1237.26.10602 Boehringer Ingelheim Investigational Site
🇺🇸San Antonio, Texas, United States
1237.26.10607 Boehringer Ingelheim Investigational Site
🇺🇸Gaffney, South Carolina, United States
1237.26.10614 Boehringer Ingelheim Investigational Site
🇺🇸Tampa, Florida, United States
1237.26.10603 Boehringer Ingelheim Investigational Site
🇺🇸Columbus, Ohio, United States
1237.26.61001 Boehringer Ingelheim Investigational Site
🇦🇺Nedlands, Western Australia, Australia
1237.26.11605 Boehringer Ingelheim Investigational Site
🇨🇦Moncton, New Brunswick, Canada
1237.26.49610 Boehringer Ingelheim Investigational Site
🇩🇪Bamberg, Germany
1237.26.49616 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.26.49609 Boehringer Ingelheim Investigational Site
🇩🇪Bochum, Germany
1237.26.49607 Boehringer Ingelheim Investigational Site
🇩🇪Dresden, Germany
1237.26.49605 Boehringer Ingelheim Investigational Site
🇩🇪Leipzig, Germany
1237.26.49608 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
1237.26.49603 Boehringer Ingelheim Investigational Site
🇩🇪Hettstedt, Germany
1237.26.49602 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
1237.26.49601 Boehringer Ingelheim Investigational Site
🇩🇪Lübeck, Germany
1237.26.49613 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1237.26.30005 Boehringer Ingelheim Investigational Site
🇬🇷Athens, Greece
1237.26.10618 Boehringer Ingelheim Investigational Site
🇺🇸Stamford, Connecticut, United States
1237.26.11608 Boehringer Ingelheim Investigational Site
🇨🇦Sarnia, Ontario, Canada
1237.26.11602 Boehringer Ingelheim Investigational Site
🇨🇦Point Claire, Quebec, Canada
1237.26.43004 Boehringer Ingelheim Investigational Site
🇦🇹Feldbach, Austria
1237.26.43002 Boehringer Ingelheim Investigational Site
🇦🇹Grieskirchen, Austria
1237.26.49615 Boehringer Ingelheim Investigational Site
🇩🇪Halberstadt, Germany
1237.26.10604 Boehringer Ingelheim Investigational Site
🇺🇸Union, South Carolina, United States
1237.26.10608 Boehringer Ingelheim Investigational Site
🇺🇸Spartanburg, South Carolina, United States
1237.26.11606 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
1237.26.10619 Boehringer Ingelheim Investigational Site
🇺🇸Clearwater, Florida, United States
1237.26.61003 Boehringer Ingelheim Investigational Site
🇦🇺Toorak Gardens, South Australia, Australia
1237.26.10617 Boehringer Ingelheim Investigational Site
🇺🇸Greenville, South Carolina, United States
1237.26.61007 Boehringer Ingelheim Investigational Site
🇦🇺Woodville, South Australia, Australia
1237.26.43006 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
1237.26.10601 Boehringer Ingelheim Investigational Site
🇺🇸Morgantown, West Virginia, United States
1237.26.61002 Boehringer Ingelheim Investigational Site
🇦🇺Daw Park, South Australia, Australia
1237.26.11611 Boehringer Ingelheim Investigational Site
🇨🇦Mirabel, Quebec, Canada
1237.26.49611 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.26.43003 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
1237.26.43001 Boehringer Ingelheim Investigational Site
🇦🇹Thalheim bei Wels, Austria
1237.26.11609 Boehringer Ingelheim Investigational Site
🇨🇦Courtice, Ontario, Canada
1237.26.11607 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
1237.26.11603 Boehringer Ingelheim Investigational Site
🇨🇦Sherbrooke, Quebec, Canada
1237.26.49606 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1237.26.11601 Boehringer Ingelheim Investigational Site
🇨🇦Windsor, Ontario, Canada
1237.26.49604 Boehringer Ingelheim Investigational Site
🇩🇪Leipzig, Germany
1237.26.49614 Boehringer Ingelheim Investigational Site
🇩🇪Schwerin, Germany
1237.26.49612 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
1237.26.42104 Boehringer Ingelheim Investigational Site
🇸🇰Humenne, Slovakia
1237.26.30002 Boehringer Ingelheim Investigational Site
🇬🇷Heraklion, Greece
1237.26.64001 Boehringer Ingelheim Investigational Site
🇳🇿Greenlane East Auckland NZ, New Zealand
1237.26.47003 Boehringer Ingelheim Investigational Site
🇳🇴Hamar, Norway
1237.26.47004 Boehringer Ingelheim Investigational Site
🇳🇴Lierskogen, Norway
1237.26.30001 Boehringer Ingelheim Investigational Site
🇬🇷Nafplio, Greece
1237.26.30004 Boehringer Ingelheim Investigational Site
🇬🇷Serres, Greece
1237.26.30003 Boehringer Ingelheim Investigational Site
🇬🇷Thessaloniki, Greece
1237.26.42103 Boehringer Ingelheim Investigational Site
🇸🇰Bardejov, Slovakia
1237.26.42102 Boehringer Ingelheim Investigational Site
🇸🇰Spisska Nova Ves, Slovakia
1237.26.42101 Boehringer Ingelheim Investigational Site
🇸🇰Vysne Hagy, Slovakia
1237.26.10616 Boehringer Ingelheim Investigational Site
🇺🇸Duluth, Georgia, United States