A Study to Determine the Effect of Tiotropium + Olodaterol Fixed Dose Combination on Exercise Endurance Time During Constant Work Rate Cycle Ergometry Test in COPD

NCT01525615 | Completed Phase 3 Results

• 2 other identifiers: 1237.152011-004253-11
• Study Type: interventional
• Target: 404
• Locations: 10 countries
• Sites: 60

Brief Summary

The primary objective of this study is to compare the effects of orally inhaled tiotropium + olodaterol fixed dose combination (2.5/5 µg; 5/5 µg) with placebo on exercise tolerance after 12 weeks of treatment in patients with COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks

  Primary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean.

  12 weeks

Secondary Outcomes (12)

• Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks

  12 weeks

• Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks

  12 weeks

• Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1

  1 day

• Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment

  6 weeks

• Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day

  1 day

Study Arms (3)

tiotropium+olodaterol low dose

EXPERIMENTAL

once daily 2 puffs, fixed dose combination (FDC) solution for inhalation Respimat

Device: Respimat inhaler; Drug: tiotropium+olodaterol (low dose)

tiotropium+olodaterol high dose

EXPERIMENTAL

once daily 2 puffs, FDC solution for inhalation Respimat

Drug: tiotropium + olodaterol (high dose); Device: Respimat inhaler

placebo

PLACEBO COMPARATOR

once daily 2 puffs, solution for inhalation Respimat

Device: Respimat inhaler; Drug: placebo to tiotropium+olodaterol

Interventions

Respimat inhaler DEVICE

Respimat inhaler

tiotropium+olodaterol low dose

tiotropium+olodaterol (low dose) DRUG

2.5 µg tiotropium + 5 µg olodaterol

tiotropium+olodaterol low dose

tiotropium + olodaterol (high dose) DRUG

5 µg tiotropium + 5 µg olodaterol

tiotropium+olodaterol high dose

placebo to tiotropium+olodaterol DRUG

comparator

placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.
• All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
• Patients must have relatively stable airway obstruction with, at visit 1:
• a post-bronchodilator 30% \<= FEV1 \<80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC \<70% at Visit 1
• Male or female patients, between 40 and 75 years (inclusive) of age on day of signing informed consent.
• Patients must be current or ex-smokers with a smoking history of more than 10 pack years Patients who have never smoked cigarettes must be excluded.
• Patients must be able to perform technically acceptable pulmonary function tests (spirometry), must be able to complete multiple symptom-limited cycle ergometry tests (and for a subset also shuttle walk tests), as required in the protocol.
• Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI).

You may not qualify if:

• Patients with a significant disease other than COPD
• Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT \> x2 ULN, SGPT \> x2 ULN, bilirubin \> x2 ULN or creatinine \> x2 ULN will be excluded regardless of clinical condition
• Patients with a history of asthma
• A diagnosis of thyrotoxicosis
• A diagnosis of paroxysmal tachycardia (\>100 beats per minute)
• A history of myocardial infarction within 1 year of screening visit (Visit 1)
• Unstable or life-threatening cardiac arrhythmia
• Hospitalized for heart failure within the past year
• Known active tuberculosis
• A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
• A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure
• A history of cystic fibrosis
• Clinically evident bronchiectasis
• A history of significant alcohol or drug abuse
• Any contraindications for exercise testing

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (60)

1237.15.01503 Boehringer Ingelheim Investigational Site

Torrance, California, United States

Location

1237.15.01512 Boehringer Ingelheim Investigational Site

Hartford, Connecticut, United States

Location

1237.15.01506 Boehringer Ingelheim Investigational Site

Springfield, Illinois, United States

Location

1237.15.01507 Boehringer Ingelheim Investigational Site

Iowa City, Iowa, United States

Location

1237.15.01504 Boehringer Ingelheim Investigational Site

Livonia, Michigan, United States

Location

1237.15.01511 Boehringer Ingelheim Investigational Site

Saint Charles, Missouri, United States

Location

1237.15.01509 Boehringer Ingelheim Investigational Site

Lebanon, New Hampshire, United States

Location

1237.15.01513 Boehringer Ingelheim Investigational Site

Charlotte, North Carolina, United States

Location

1237.15.01514 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1237.15.01516 Boehringer Ingelheim Investigational Site

Pittsburgh, Pennsylvania, United States

Location

1237.15.01508 Boehringer Ingelheim Investigational Site

Easley, South Carolina, United States

Location

1237.15.01501 Boehringer Ingelheim Investigational Site

Greenville, South Carolina, United States

Location

1237.15.01505 Boehringer Ingelheim Investigational Site

Spartanburg, South Carolina, United States

Location

1237.15.01502 Boehringer Ingelheim Investigational Site

Union, South Carolina, United States

Location

1237.15.01510 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

1237.15.54502 Boehringer Ingelheim Investigational Site

Buenos Aires, Argentina

Location

1237.15.54501 Boehringer Ingelheim Investigational Site

Mendonza, Argentina

Location

1237.15.54503 Boehringer Ingelheim Investigational Site

Provincia de Buenos Aires, Argentina

Location

1237.15.11501 Boehringer Ingelheim Investigational Site

Hamilotn, Ontario, Canada

Location

1237.15.11503 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1237.15.11504 Boehringer Ingelheim Investigational Site

Kingston, Ontario, Canada

Location

1237.15.11505 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1237.15.11502 Boehringer Ingelheim Investigational Site

Ste-Foy, Quebec, Canada

Location

1237.15.35851 Boehringer Ingelheim Investigational Site

Helsinki, Finland

Location

1237.15.35853 Boehringer Ingelheim Investigational Site

Turku, Finland

Location

1237.15.35852 Boehringer Ingelheim Investigational Site

Vaasa, Finland

Location

1237.15.33502 Boehringer Ingelheim Investigational Site

Nîmes, France

Location

1237.15.33504 Boehringer Ingelheim Investigational Site

Pessac, France

Location

1237.15.33501 Boehringer Ingelheim Investigational Site

Strasbourg, France

Location

1237.15.49507 Boehringer Ingelheim Investigational Site

Aschaffenburg, Germany

Location

1237.15.49502 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.15.49504 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.15.49501 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Location

1237.15.49509 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1237.15.49505 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1237.15.49508 Boehringer Ingelheim Investigational Site

Koblenz, Germany

Location

1237.15.49506 Boehringer Ingelheim Investigational Site

Wiesloch, Germany

Location

1237.15.36504 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

1237.15.36501 Boehringer Ingelheim Investigational Site

Deszk, Hungary

Location

1237.15.36503 Boehringer Ingelheim Investigational Site

Nyíregyháza, Hungary

Location

1237.15.36502 Boehringer Ingelheim Investigational Site

Pécs, Hungary

Location

1237.15.39512 Boehringer Ingelheim Investigational Site

Ferrara, Italy

Location

1237.15.39504 Boehringer Ingelheim Investigational Site

Parma, Italy

Location

1237.15.39503 Boehringer Ingelheim Investigational Site

Pavia, Italy

Location

1237.15.39501 Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

1237.15.39509 Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

1237.15.39511 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1237.15.39508 Boehringer Ingelheim Investigational Site

Sesto San Giovanni (MI), Italy

Location

1237.15.39506 Boehringer Ingelheim Investigational Site

Trieste, Italy

Location

1237.15.34506 Boehringer Ingelheim Investigational Site

Alicante, Spain

Location

1237.15.34501 Boehringer Ingelheim Investigational Site

Barakaldo (Bilbao), Spain

Location

1237.15.34507 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1237.15.34009 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1237.15.34001 Boehringer Ingelheim Investigational Site

Santander, Spain

Location

1237.15.44152 Boehringer Ingelheim Investigational Site

Leicester, United Kingdom

Location

1237.15.44154 Boehringer Ingelheim Investigational Site

Liverpool, United Kingdom

Location

1237.15.44153 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1237.15.44151 Boehringer Ingelheim Investigational Site

Manchester, United Kingdom

Location

1237.15.44155 Boehringer Ingelheim Investigational Site

Norwich, United Kingdom

Location

1237.15.44158 Boehringer Ingelheim Investigational Site

Plymouth, United Kingdom

Location

Related Publications (1)

• Maltais F, O'Donnell D, Galdiz Iturri JB, Kirsten AM, Singh D, Hamilton A, Tetzlaff K, Zhao Y, Casaburi R. Effect of 12 weeks of once-daily tiotropium/olodaterol on exercise endurance during constant work-rate cycling and endurance shuttle walking in chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753465818755091. doi: 10.1177/1753465818755091.

  PMID: 29439648 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

tiotropium-olodaterol; 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: February 1, 2012
• First Posted: February 3, 2012
• Study Start: February 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: August 29, 2016
• Results First Posted: September 15, 2015

Record last verified: 2016-07

Locations

IT (8); CA (5); GB (6); ES (5); FR (3); HU (4); US (15); FI (3); AR (3); DE (8)