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

NCT02006732 | Completed Phase 3 Results

• 2 other identifiers: 1237.262013-002264-24
• Study Type: interventional
• Target: 809
• Locations: 10 countries
• Sites: 73

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (4)

• FEV1 AUC0-3h Response

  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.

  baseline and 12 weeks

• Trough FEV1 Response (Change From Baseline)

  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.

  baseline and 12 weeks

• St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Data From This Individual Study

  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.

  12 weeks treatment

• St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Combined Dataset From This Study and the Replicate Study NCT01964352

  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.

  12 weeks treatment

Secondary Outcomes (4)

• Trough Forced Vital Capacity (FVC) Response (Change From Baseline)

  baseline and 12 weeks

• TDI Focal Score Based on Data From This Individual Study

  12 weeks

• TDI Focal Score Based on Combined Dataset From This Study and the Replicate Study NCT01964352

  12 weeks

• FVC AUC0-3h Response (Change From Baseline)

  baseline and 12 weeks

Study Arms (4)

tiotropium + olodaterol low dose

EXPERIMENTAL

Once daily 2 puffs solution for inhalation Respimat

Drug: olodaterol; Drug: tiotropium

tiotropium + olodaterol high dose

EXPERIMENTAL

Once daily 2 puffs solution for inhalation Respimat

Drug: olodaterol; Drug: tiotropium

tiotropium

ACTIVE COMPARATOR

Once daily 2 puffs solution for inhalation Respimat

Drug: tiotropium

placebo

PLACEBO COMPARATOR

Once daily 2 puffs solution for inhalation Respimat

Drug: placebo

Interventions

olodaterol DRUG

fixed dose combination

tiotropium + olodaterol high dose; tiotropium + olodaterol low dose

tiotropium DRUG

fixed dose combination

tiotropium; tiotropium + olodaterol high dose; tiotropium + olodaterol low dose

placebo DRUG

placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis chronic obstructive pulmonary disease
• Relatively stable airway obstruction with post FEV1 \>=30 and \< 80% predicted normal and post FEV1/ FVC \< 70%
• Male or female patients, 40 years of age or more
• Smoking history more than 10 pack years

You may not qualify if:

• Significant diseases other than COPD
• History of asthma
• COPD exacerbation in previous 3 months
• Completion of pulmonary rehabilitation program within previous 6 weeks or current participation in pulmonary rehabilitation program.
• Pregnant or nursing women
• Patients unable to comply with pulmonary medication restrictions

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (78)

1237.26.10620 Boehringer Ingelheim Investigational Site

Jasper, Alabama, United States

Location

1237.26.10618 Boehringer Ingelheim Investigational Site

Stamford, Connecticut, United States

Location

1237.26.10619 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

Location

1237.26.10614 Boehringer Ingelheim Investigational Site

Tampa, Florida, United States

Location

1237.26.10616 Boehringer Ingelheim Investigational Site

Duluth, Georgia, United States

Location

1237.26.10613 Boehringer Ingelheim Investigational Site

St Louis, Missouri, United States

Location

1237.26.10615 Boehringer Ingelheim Investigational Site

Greensboro, North Carolina, United States

Location

1237.26.10603 Boehringer Ingelheim Investigational Site

Columbus, Ohio, United States

Location

1237.26.10621 Boehringer Ingelheim Investigational Site

Dayton, Ohio, United States

Location

1237.26.10612 Boehringer Ingelheim Investigational Site

Toledo, Ohio, United States

Location

1237.26.10605 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

1237.26.10606 Boehringer Ingelheim Investigational Site

Medford, Oregon, United States

Location

1237.26.10610 Boehringer Ingelheim Investigational Site

East Providence, Rhode Island, United States

Location

1237.26.10607 Boehringer Ingelheim Investigational Site

Gaffney, South Carolina, United States

Location

1237.26.10617 Boehringer Ingelheim Investigational Site

Greenville, South Carolina, United States

Location

1237.26.10608 Boehringer Ingelheim Investigational Site

Spartanburg, South Carolina, United States

Location

1237.26.10604 Boehringer Ingelheim Investigational Site

Union, South Carolina, United States

Location

1237.26.10609 Boehringer Ingelheim Investigational Site

Boerne, Texas, United States

Location

1237.26.10602 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

Location

1237.26.10601 Boehringer Ingelheim Investigational Site

Morgantown, West Virginia, United States

Location

1237.26.61004 Boehringer Ingelheim Investigational Site

Concord, New South Wales, Australia

Location

1237.26.61002 Boehringer Ingelheim Investigational Site

Daw Park, South Australia, Australia

Location

1237.26.61003 Boehringer Ingelheim Investigational Site

Toorak Gardens, South Australia, Australia

Location

1237.26.61007 Boehringer Ingelheim Investigational Site

Woodville, South Australia, Australia

Location

1237.26.61005 Boehringer Ingelheim Investigational Site

Murdoch, Western Australia, Australia

Location

1237.26.61001 Boehringer Ingelheim Investigational Site

Nedlands, Western Australia, Australia

Location

1237.26.43004 Boehringer Ingelheim Investigational Site

Feldbach, Austria

Location

1237.26.43002 Boehringer Ingelheim Investigational Site

Grieskirchen, Austria

Location

1237.26.43003 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

1237.26.43006 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

1237.26.43001 Boehringer Ingelheim Investigational Site

Thalheim bei Wels, Austria

Location

1237.26.11605 Boehringer Ingelheim Investigational Site

Moncton, New Brunswick, Canada

Location

1237.26.11609 Boehringer Ingelheim Investigational Site

Courtice, Ontario, Canada

Location

1237.26.11608 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

Location

1237.26.11606 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1237.26.11607 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1237.26.11601 Boehringer Ingelheim Investigational Site

Windsor, Ontario, Canada

Location

1237.26.11611 Boehringer Ingelheim Investigational Site

Mirabel, Quebec, Canada

Location

1237.26.11602 Boehringer Ingelheim Investigational Site

Point Claire, Quebec, Canada

Location

1237.26.11603 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

Location

1237.26.49610 Boehringer Ingelheim Investigational Site

Bamberg, Germany

Location

1237.26.49611 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.26.49616 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.26.49609 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

1237.26.49607 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

1237.26.49612 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

1237.26.49615 Boehringer Ingelheim Investigational Site

Halberstadt, Germany

Location

1237.26.49606 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1237.26.49608 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1237.26.49603 Boehringer Ingelheim Investigational Site

Hettstedt, Germany

Location

1237.26.49604 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1237.26.49605 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1237.26.49601 Boehringer Ingelheim Investigational Site

Lübeck, Germany

Location

1237.26.49602 Boehringer Ingelheim Investigational Site

Rüdersdorf, Germany

Location

1237.26.49614 Boehringer Ingelheim Investigational Site

Schwerin, Germany

Location

1237.26.49613 Boehringer Ingelheim Investigational Site

Wiesloch, Germany

Location

1237.26.30005 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1237.26.30002 Boehringer Ingelheim Investigational Site

Heraklion, Greece

Location

1237.26.30001 Boehringer Ingelheim Investigational Site

Nafplion, Greece

Location

1237.26.30004 Boehringer Ingelheim Investigational Site

Serres, Greece

Location

1237.26.30003 Boehringer Ingelheim Investigational Site

Thessaloniki, Greece

Location

1237.26.64001 Boehringer Ingelheim Investigational Site

Greenlane East Auckland NZ, New Zealand

Location

1237.26.47003 Boehringer Ingelheim Investigational Site

Hamar, Norway

Location

1237.26.47001 Boehringer Ingelheim Investigational Site

Hønefoss, Norway

Location

1237.26.47002 Boehringer Ingelheim Investigational Site

Kløfta, Norway

Location

1237.26.47004 Boehringer Ingelheim Investigational Site

Lierskogen, Norway

Location

1237.26.42103 Boehringer Ingelheim Investigational Site

Bardejov, Slovakia

Location

1237.26.42104 Boehringer Ingelheim Investigational Site

Humenné, Slovakia

Location

1237.26.42102 Boehringer Ingelheim Investigational Site

Spišská Nová Ves, Slovakia

Location

1237.26.42101 Boehringer Ingelheim Investigational Site

Vyšné Hágy, Slovakia

Location

1237.26.27601 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1237.26.27602 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1237.26.27604 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1237.26.27605 Boehringer Ingelheim Investigational Site

Durban, South Africa

Location

1237.26.46004 Boehringer Ingelheim Investigational Site

Höllviken, Sweden

Location

1237.26.46001 Boehringer Ingelheim Investigational Site

Lund, Sweden

Location

1237.26.46002 Boehringer Ingelheim Investigational Site

Stockholm, Sweden

Location

1237.26.46003 Boehringer Ingelheim Investigational Site

Uddevalla, Sweden

Location

Related Publications (4)

• Buhl R, de la Hoz A, Xue W, Singh D, Ferguson GT. Efficacy of Tiotropium/Olodaterol Compared with Tiotropium as a First-Line Maintenance Treatment in Patients with COPD Who Are Naive to LAMA, LABA and ICS: Pooled Analysis of Four Clinical Trials. Adv Ther. 2020 Oct;37(10):4175-4189. doi: 10.1007/s12325-020-01411-0. Epub 2020 Jul 15.

  PMID: 32671684 DERIVED

• Buhl R, Singh D, de la Hoz A, Xue W, Ferguson GT. Benefits of Tiotropium/Olodaterol Compared with Tiotropium in Patients with COPD Receiving only LAMA at Baseline: Pooled Analysis of the TONADO(R) and OTEMTO(R) Studies. Adv Ther. 2020 Aug;37(8):3485-3499. doi: 10.1007/s12325-020-01373-3. Epub 2020 May 27.

  PMID: 32462607 DERIVED

• Singh D, Gaga M, Schmidt O, Bjermer L, Gronke L, Voss F, Ferguson GT. Effects of tiotropium + olodaterol versus tiotropium or placebo by COPD disease severity and previous treatment history in the OTEMTO(R) studies. Respir Res. 2016 Jun 18;17(1):73. doi: 10.1186/s12931-016-0387-7.

  PMID: 27316465 DERIVED

• Singh D, Ferguson GT, Bolitschek J, Gronke L, Hallmann C, Bennett N, Abrahams R, Schmidt O, Bjermer L. Tiotropium + olodaterol shows clinically meaningful improvements in quality of life. Respir Med. 2015 Oct;109(10):1312-9. doi: 10.1016/j.rmed.2015.08.002. Epub 2015 Aug 12.

  PMID: 26320402 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

olodaterol; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: December 10, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 20, 2016
• Results First Posted: January 20, 2016

Record last verified: 2015-12

Locations

CA (9); AU (6); NO (4); SL (4); SE (4); ZA (4); DE (16); NZ (1); US (20); GR (5)