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

NCT01964352 | Completed Phase 3 Results

• 2 other identifiers: 1237.252013-002243-29
• Study Type: interventional
• Target: 813
• Locations: 10 countries
• Sites: 77

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 (3)

• 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

  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.

  12 weeks treatment

Secondary Outcomes (3)

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

  baseline and 12 weeks

• TDI Focal Score

  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: tiotropium; Drug: olodaterol

tiotropium + olodaterol high dose

EXPERIMENTAL

Once daily 2 puffs solution for inhalation Respimat

Drug: tiotropium; Drug: olodaterol

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

tiotropium DRUG

fixed dose combination

tiotropium + olodaterol high dose

placebo DRUG

placebo

olodaterol DRUG

fixed dose combination

tiotropium + olodaterol high dose

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 (77)

1237.25.10504 Boehringer Ingelheim Investigational Site

Wheat Ridge, Colorado, United States

Location

1237.25.10507 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

Location

1237.25.10517 Boehringer Ingelheim Investigational Site

Panama City, Florida, United States

Location

1237.25.10505 Boehringer Ingelheim Investigational Site

Coeur d'Alene, Idaho, United States

Location

1237.25.10516 Boehringer Ingelheim Investigational Site

Ann Arbor, Michigan, United States

Location

1237.25.10509 Boehringer Ingelheim Investigational Site

Livonia, Michigan, United States

Location

1237.25.10519 Boehringer Ingelheim Investigational Site

Charlotte, North Carolina, United States

Location

1237.25.10503 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

Location

1237.25.10518 Boehringer Ingelheim Investigational Site

Columbia, Ohio, United States

Location

1237.25.10502 Boehringer Ingelheim Investigational Site

Columbus, Ohio, United States

Location

1237.25.10511 Boehringer Ingelheim Investigational Site

Dublin, Ohio, United States

Location

1237.25.10514 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1237.25.10513 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

1237.25.10515 Boehringer Ingelheim Investigational Site

Easley, South Carolina, United States

Location

1237.25.10506 Boehringer Ingelheim Investigational Site

Greenville, South Carolina, United States

Location

1237.25.10501 Boehringer Ingelheim Investigational Site

Rock Hill, South Carolina, United States

Location

1237.25.10508 Boehringer Ingelheim Investigational Site

Spartanburg, South Carolina, United States

Location

1237.25.10520 Boehringer Ingelheim Investigational Site

Killeen, Texas, United States

Location

1237.25.10510 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

1237.25.10521 Boehringer Ingelheim Investigational Site

Spokane, Washington, United States

Location

1237.25.32001 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1237.25.32004 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1237.25.32005 Boehringer Ingelheim Investigational Site

Eupen, Belgium

Location

1237.25.32003 Boehringer Ingelheim Investigational Site

Lebbeke, Belgium

Location

1237.25.32002 Boehringer Ingelheim Investigational Site

Turnhout, Belgium

Location

1237.25.11508 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1237.25.11504 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

Location

1237.25.11501 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1237.25.11505 Boehringer Ingelheim Investigational Site

Burlington, Ontario, Canada

Location

1237.25.11507 Boehringer Ingelheim Investigational Site

Grimsby, Ontario, Canada

Location

1237.25.11510 Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

Location

1237.25.11502 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

Location

1237.25.11506 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

Location

1237.25.11509 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

Location

1237.25.42003 Boehringer Ingelheim Investigational Site

Jindřichův Hradec, Czechia

Location

1237.25.42005 Boehringer Ingelheim Investigational Site

Karlovy Vary-Drahovice, Czechia

Location

1237.25.42002 Boehringer Ingelheim Investigational Site

Neratovice, Czechia

Location

1237.25.42001 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1237.25.42004 Boehringer Ingelheim Investigational Site

Rokycany, Czechia

Location

1237.25.45003 Boehringer Ingelheim Investigational Site

Aalborg, Denmark

Location

1237.25.45002 Boehringer Ingelheim Investigational Site

Hellerup, Denmark

Location

1237.25.45001 Boehringer Ingelheim Investigational Site

Odense, Denmark

Location

1237.25.45004 Boehringer Ingelheim Investigational Site

Silkeborg, Denmark

Location

1237.25.35802 Boehringer Ingelheim Investigational Site

Pori, Finland

Location

1237.25.35801 Boehringer Ingelheim Investigational Site

Turku, Finland

Location

1237.25.35803 Boehringer Ingelheim Investigational Site

Turku, Finland

Location

1237.25.49504 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.25.49508 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.25.49510 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.25.49501 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Location

1237.25.49505 Boehringer Ingelheim Investigational Site

Halle, Germany

Location

1237.25.49506 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1237.25.49515 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1237.25.49509 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1237.25.49514 Boehringer Ingelheim Investigational Site

Koblenz, Germany

Location

1237.25.49507 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1237.25.49502 Boehringer Ingelheim Investigational Site

Neu-Isenburg, Germany

Location

1237.25.49516 Boehringer Ingelheim Investigational Site

Oschersleben, Germany

Location

1237.25.49511 Boehringer Ingelheim Investigational Site

Rodgau, Germany

Location

1237.25.49503 Boehringer Ingelheim Investigational Site

Rosenheim, Germany

Location

1237.25.49513 Boehringer Ingelheim Investigational Site

Teuchern, Germany

Location

1237.25.27506 Boehringer Ingelheim Investigational Site

Bloemfontein, South Africa

Location

1237.25.27501 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1237.25.27505 Boehringer Ingelheim Investigational Site

eMkhomazi, South Africa

Location

1237.25.27504 Boehringer Ingelheim Investigational Site

Morningside, Sandton, South Africa

Location

1237.25.27502 Boehringer Ingelheim Investigational Site

Parow, South Africa

Location

1237.25.27503 Boehringer Ingelheim Investigational Site

Pretoria, South Africa

Location

1237.25.34003 Boehringer Ingelheim Investigational Site

Alicante, Spain

Location

1237.25.34007 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1237.25.34001 Boehringer Ingelheim Investigational Site

Mérida, Spain

Location

1237.25.34002 Boehringer Ingelheim Investigational Site

Pozuelo de Alarcón, Spain

Location

1237.25.34004 Boehringer Ingelheim Investigational Site

Vic, Spain

Location

1237.25.44002 Boehringer Ingelheim Investigational Site

Bradford, United Kingdom

Location

1237.25.44001 Boehringer Ingelheim Investigational Site

Chertsey, United Kingdom

Location

1237.25.44004 Boehringer Ingelheim Investigational Site

Chester, United Kingdom

Location

1237.25.44005 Boehringer Ingelheim Investigational Site

Chippenham, United Kingdom

Location

1237.25.44003 Boehringer Ingelheim Investigational Site

Wolverhampton, United Kingdom

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

Tiotropium Bromide; olodaterol

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: October 17, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 25, 2015
• Results First Posted: November 25, 2015

Record last verified: 2015-10

Locations

CA (9); DK (4); ZA (6); CZ (5); BE (5); US (20); DE (15); GB (5); FI (3); ES (5)