MedPath

Tiotropium + Olodaterol Fixed Dose Combination (FDC) in Chronic Obstructive Pulmonary Disease (OTEMTO 1)

Phase 3
Completed
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
Registration Number
NCT01964352
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
813
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
tiotropium + olodaterol low dosetiotropiumOnce daily 2 puffs solution for inhalation Respimat
placeboplaceboOnce daily 2 puffs solution for inhalation Respimat
tiotropiumtiotropiumOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol low doseolodaterolOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol high dosetiotropiumOnce daily 2 puffs solution for inhalation Respimat
tiotropium + olodaterol high doseolodaterolOnce 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 Score12 weeks treatment

This endpoint was evaluated based on the data from this individual trial and also based on the data from the combined dataset from this trial and the replicate study NCT02006732. The results for the combined dataset are included in the disclosure for NCT02006732 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
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.

TDI Focal Score12 weeks

This endpoint was evaluated based on the data from this individual trial and also based on the data from the combined dataset from this trial and the replicate study NCT02006732. The results for the combined dataset are included in the disclosure for NCT02006732 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.

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.

Trial Locations

Locations (77)

1237.25.10508 Boehringer Ingelheim Investigational Site

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Spartanburg, South Carolina, United States

1237.25.32002 Boehringer Ingelheim Investigational Site

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Turnhout, Belgium

1237.25.32004 Boehringer Ingelheim Investigational Site

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Brussels, Belgium

1237.25.10501 Boehringer Ingelheim Investigational Site

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Rock Hill, South Carolina, United States

1237.25.10514 Boehringer Ingelheim Investigational Site

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Philadelphia, Pennsylvania, United States

1237.25.10510 Boehringer Ingelheim Investigational Site

🇺🇸

Richmond, Virginia, United States

1237.25.10507 Boehringer Ingelheim Investigational Site

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Clearwater, Florida, United States

1237.25.11507 Boehringer Ingelheim Investigational Site

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Grimsby, Ontario, Canada

1237.25.34003 Boehringer Ingelheim Investigational Site

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Alicante, Spain

1237.25.42002 Boehringer Ingelheim Investigational Site

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Neratovice, Czech Republic

1237.25.27505 Boehringer Ingelheim Investigational Site

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Umkomaas, South Africa

1237.25.34004 Boehringer Ingelheim Investigational Site

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Vic, Spain

1237.25.44004 Boehringer Ingelheim Investigational Site

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Chester, United Kingdom

1237.25.11508 Boehringer Ingelheim Investigational Site

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Calgary, Alberta, Canada

1237.25.34007 Boehringer Ingelheim Investigational Site

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Barcelona, Spain

1237.25.42005 Boehringer Ingelheim Investigational Site

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Karlovy Vary-Drahovice, Czech Republic

1237.25.11506 Boehringer Ingelheim Investigational Site

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Quebec, Canada

1237.25.27503 Boehringer Ingelheim Investigational Site

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Pretoria, South Africa

1237.25.44005 Boehringer Ingelheim Investigational Site

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Chippenham, United Kingdom

1237.25.49504 Boehringer Ingelheim Investigational Site

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Berlin, Germany

1237.25.42003 Boehringer Ingelheim Investigational Site

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Jindrichuv Hradec, Czech Republic

1237.25.27502 Boehringer Ingelheim Investigational Site

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Parow, South Africa

1237.25.27501 Boehringer Ingelheim Investigational Site

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Cape Town, South Africa

1237.25.34001 Boehringer Ingelheim Investigational Site

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Mérida, Spain

1237.25.34002 Boehringer Ingelheim Investigational Site

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Pozuelo de Alarcón, Spain

1237.25.49505 Boehringer Ingelheim Investigational Site

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Halle/Saale, Germany

1237.25.49510 Boehringer Ingelheim Investigational Site

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Berlin, Germany

1237.25.49506 Boehringer Ingelheim Investigational Site

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Hamburg, Germany

1237.25.45001 Boehringer Ingelheim Investigational Site

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Odense, Denmark

1237.25.45004 Boehringer Ingelheim Investigational Site

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Silkeborg, Denmark

1237.25.45003 Boehringer Ingelheim Investigational Site

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Ålborg, Denmark

1237.25.11502 Boehringer Ingelheim Investigational Site

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Quebec, Canada

1237.25.11509 Boehringer Ingelheim Investigational Site

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Sherbrooke,, Quebec, Canada

1237.25.44001 Boehringer Ingelheim Investigational Site

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Chertsey, United Kingdom

1237.25.49501 Boehringer Ingelheim Investigational Site

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Großhansdorf, Germany

1237.25.49515 Boehringer Ingelheim Investigational Site

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Hamburg, Germany

1237.25.49502 Boehringer Ingelheim Investigational Site

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Neu-Isenburg, Germany

1237.25.49514 Boehringer Ingelheim Investigational Site

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Koblenz, Germany

1237.25.49513 Boehringer Ingelheim Investigational Site

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Teuchern, Germany

1237.25.10503 Boehringer Ingelheim Investigational Site

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Cincinnati, Ohio, United States

1237.25.10504 Boehringer Ingelheim Investigational Site

🇺🇸

Wheat Ridge, Colorado, United States

1237.25.10517 Boehringer Ingelheim Investigational Site

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Panama City, Florida, United States

1237.25.10516 Boehringer Ingelheim Investigational Site

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Ann Arbor, Michigan, United States

1237.25.10509 Boehringer Ingelheim Investigational Site

🇺🇸

Livonia, Michigan, United States

1237.25.10519 Boehringer Ingelheim Investigational Site

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Charlotte, North Carolina, United States

1237.25.10518 Boehringer Ingelheim Investigational Site

🇺🇸

Columbia, Ohio, United States

1237.25.10502 Boehringer Ingelheim Investigational Site

🇺🇸

Columbus, Ohio, United States

1237.25.10513 Boehringer Ingelheim Investigational Site

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Charleston, South Carolina, United States

1237.25.42004 Boehringer Ingelheim Investigational Site

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Rokycany, Czech Republic

1237.25.35802 Boehringer Ingelheim Investigational Site

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Pori, Finland

1237.25.49508 Boehringer Ingelheim Investigational Site

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Berlin, Germany

1237.25.45002 Boehringer Ingelheim Investigational Site

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Hellerup, Denmark

1237.25.49509 Boehringer Ingelheim Investigational Site

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Hannover, Germany

1237.25.49503 Boehringer Ingelheim Investigational Site

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Rosenheim, Germany

1237.25.27504 Boehringer Ingelheim Investigational Site

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Morningside, Sandton, South Africa

1237.25.27506 Boehringer Ingelheim Investigational Site

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Bloemfontein, South Africa

1237.25.10506 Boehringer Ingelheim Investigational Site

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Greenville, South Carolina, United States

1237.25.10505 Boehringer Ingelheim Investigational Site

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Coeur d'Alene, Idaho, United States

1237.25.44002 Boehringer Ingelheim Investigational Site

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Bradford, United Kingdom

1237.25.10511 Boehringer Ingelheim Investigational Site

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Dublin, Ohio, United States

1237.25.10515 Boehringer Ingelheim Investigational Site

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Easley, South Carolina, United States

1237.25.11504 Boehringer Ingelheim Investigational Site

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Edmonton, Alberta, Canada

1237.25.11505 Boehringer Ingelheim Investigational Site

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Burlington, Ontario, Canada

1237.25.10521 Boehringer Ingelheim Investigational Site

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Spokane, Washington, United States

1237.25.11510 Boehringer Ingelheim Investigational Site

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Ottawa, Ontario, Canada

1237.25.49507 Boehringer Ingelheim Investigational Site

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Mainz, Germany

1237.25.49516 Boehringer Ingelheim Investigational Site

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Oschersleben, Germany

1237.25.44003 Boehringer Ingelheim Investigational Site

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Wolverhampton, United Kingdom

1237.25.49511 Boehringer Ingelheim Investigational Site

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Rodgau, Germany

1237.25.32005 Boehringer Ingelheim Investigational Site

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Eupen, Belgium

1237.25.32001 Boehringer Ingelheim Investigational Site

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Brussel, Belgium

1237.25.42001 Boehringer Ingelheim Investigational Site

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Prague, Czech Republic

1237.25.32003 Boehringer Ingelheim Investigational Site

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Lebbeke, Belgium

1237.25.35803 Boehringer Ingelheim Investigational Site

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Turku, Finland

1237.25.35801 Boehringer Ingelheim Investigational Site

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Turku, Finland

1237.25.11501 Boehringer Ingelheim Investigational Site

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Vancouver, British Columbia, Canada

1237.25.10520 Boehringer Ingelheim Investigational Site

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Killeen, Texas, United States

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