Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD

November 27, 2013 updated by: Boehringer Ingelheim

Effect of Inhalation of a Free Combination of Tiotropium Once Daily 18 Mcg and Salmeterol Twice Daily 50 Mcg Versus a Fixed Combination of Fluticasone and Salmeterol Twice Daily (500/50 Mcg) on Static Lung Volumes and Exercise Tolerance in COPD Patients (a Randomised, Double-blind, Double Dummy, 16 (2 x 8) Weeks, Crossover Study).

The primary objective of this study is to demonstrate that treatment with a free combination of tiotropium and salmeterol provides superior improvement in static lung volumes and exercise tolerance compared to a fixed combination of fluticasone and salmeterol in patients with COPD.

The secondary objective includes assessment of safety.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

344

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Gänserndorf, Austria
        • 205.334.4309 Boehringer Ingelheim Investigational Site
      • Hallein, Austria
        • 205.334.4308 Boehringer Ingelheim Investigational Site
      • Leoben, Austria
        • 205.334.4306 Boehringer Ingelheim Investigational Site
      • Linz, Austria
        • 205.334.4301 Boehringer Ingelheim Investigational Site
      • Neumarkt am Wallersee, Austria
        • 205.334.4302 Boehringer Ingelheim Investigational Site
      • Salzburg, Austria
        • 205.334.4305 Boehringer Ingelheim Investigational Site
  • Canada
      • Quebec, Canada
        • 205.334.1006 Boehringer Ingelheim Investigational Site
    • British Columbia
      • Vancouver, British Columbia, Canada
        • 205.334.1009 Boehringer Ingelheim Investigational Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • 205.334.1003 Boehringer Ingelheim Investigational Site
    • Ontario
      • Hamilton, Ontario, Canada
        • 205.334.1005 Boehringer Ingelheim Investigational Site
      • Kingston, Ontario, Canada
        • 205.334.1008 Boehringer Ingelheim Investigational Site
      • Ottawa, Ontario, Canada
        • 205.334.1004 Boehringer Ingelheim Investigational Site
      • Toronto, Ontario, Canada
        • 205.334.1010 Boehringer Ingelheim Investigational Site
    • Quebec
      • Montreal, Quebec, Canada
        • 205.334.1001 Boehringer Ingelheim Investigational Site
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
        • 205.334.1007 Boehringer Ingelheim Investigational Site
  • France
      • Beuvry, France
        • 205.334.3303A Boehringer Ingelheim Investigational Site
      • Beuvry, France
        • 205.334.3303B Boehringer Ingelheim Investigational Site
      • Créteil, France
        • 205.334.3305A Boehringer Ingelheim Investigational Site
      • Grenoble, France
        • 205.334.3301A Boehringer Ingelheim Investigational Site
      • St Priest en Jarez, France
        • 205.334.3304A Boehringer Ingelheim Investigational Site
      • Strasbourg, France
        • 205.334.3306A Boehringer Ingelheim Investigational Site
      • Strasbourg, France
        • 205.334.3306B Boehringer Ingelheim Investigational Site
      • Toulouse, France
        • 205.334.3302A Boehringer Ingelheim Investigational Site
      • Toulouse, France
        • 205.334.3302B Boehringer Ingelheim Investigational Site
  • Germany
      • Berlin, Germany
        • 205.334.4908 Boehringer Ingelheim Investigational Site
      • Berlin, Germany
        • 205.334.4909 Boehringer Ingelheim Investigational Site
      • Donaustauf, Germany
        • 205.334.4904 Boehringer Ingelheim Investigational Site
      • Großhansdorf, Germany
        • 205.334.4901 Boehringer Ingelheim Investigational Site
      • Kiel, Germany
        • 205.334.4907 Boehringer Ingelheim Investigational Site
      • Köln, Germany
        • 205.334.4902 Boehringer Ingelheim Investigational Site
  • Italy
      • Catania, Italy
        • 205.334.39007 Boehringer Ingelheim Investigational Site
      • Gaiato Pavullo (mo), Italy
        • 205.334.39002 Boehringer Ingelheim Investigational Site
      • Milano, Italy
        • 205.334.39004 Boehringer Ingelheim Investigational Site
      • Pisa, Italy
        • 205.334.39001 Boehringer Ingelheim Investigational Site
      • Roma, Italy
        • 205.334.39005 Boehringer Ingelheim Investigational Site
      • Roma, Italy
        • 205.334.39006 Boehringer Ingelheim Investigational Site
  • Russian Federation
      • Moscow, Russian Federation
        • 205.334.7001 Boehringer Ingelheim Investigational Site
      • Moscow, Russian Federation
        • 205.334.7002 Boehringer Ingelheim Investigational Site
      • St. Petersburg, Russian Federation
        • 205.334.7003 Boehringer Ingelheim Investigational Site
  • Sweden
      • Jönköping, Sweden
        • 205.334.46003 Boehringer Ingelheim Investigational Site
      • Lund, Sweden
        • 205.334.46002 Boehringer Ingelheim Investigational Site
      • Uppsala, Sweden
        • 205.334.46001 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications.
  2. The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD).
  3. The patient has relatively stable, moderate to severe airway obstruction.

  4. The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):

    1. Males Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 4.30 x Height [metres] minus 0.029 x Age [years] minus 2.49
    2. Females Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 3.95 x Height [metres] minus 0.025 x Age [years] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
    3. Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.34 x Height [metres] + 0.009 x Age [years] minus 1.09
    4. Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.24 x Height [metres] + 0.001 x Age [years] minus 1.00
  5. The patient is at least 40 years and less than or equal to 75 years old.
  6. The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year.
  7. The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
  8. The patient is able to inhale the trial medication from the HandiHaler device.
  9. The patient is able to inhale the trial medication from the Diskus/Accuhaler device.

Exclusion Criteria:

  1. a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing),
  2. a recent history of myocardial infarction within one year.
  3. a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3.
  4. daytime supplemental oxygen.
  5. a diagnosis of known active tuberculosis.
  6. a history of cancer within the last 5 years.
  7. a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
  8. thoracotomy with pulmonary resection.
  9. an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD)
  10. a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system.
  11. a known symptomatic prostatic hypertrophy or bladder neck obstruction.
  12. a known moderate or severe renal insufficiency.
  13. a known narrow-angle glaucoma.
  14. a known untreated hypokalemia.
  15. a known untreated thyrotoxicosis.
  16. a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3.
  17. treatment with cromolyn sodium or nedocromil sodium
  18. treatment with antihistamines or antileukotrienes.
  19. treatment with tiotropium for 1 month before Visit 1.
  20. treatment with oral corticosteroid medication.
  21. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
  22. a history of or active alcohol or drug abuse.
  23. an investigational drug within 1 month or 10 half lives
  24. a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea.
  25. participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD).
  26. treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants.
  27. participation in another study.
  28. more than eight puffs of salbutamol/day during the run-in period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Crossover Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-dose TGV(FRC) (After 8 Weeks)
Time Frame: 8 weeks
Post-dose TGV(FRC) (Thoracic Gas Volume; co-primary endpoint) after 8 weeks
8 weeks
Endurance Time (After 8 Weeks)
Time Frame: 8 weeks
Endurance time to the point of symptom limitation after 8 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-dose TGV(FRC) (After 4 Weeks)
Time Frame: 4 weeks
Post-dose TGV(FRC) (Thoracic Gas Volume) after 4 weeks
4 weeks
Endurance Time (After 4 Weeks)
Time Frame: 4 weeks
Endurance time to the point of symptom limitation after 4 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Trough TGV(FRC) (Thoracic Gas Volume) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Trough TGV(FRC) (Thoracic Gas Volume) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Trough RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Trough RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Post-dose RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Post-dose RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Trough IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Trough IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Post-dose IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Post-dose IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Trough IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Trough IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Post-dose IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Post-dose IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Trough TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Trough TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes
Time Frame: 8 weeks
Post-dose TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes
Time Frame: 4 weeks
Post-dose TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes (Percent)
Time Frame: 8 weeks
Trough RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes (Percent)
Time Frame: 4 weeks
Trough RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes (Percent)
Time Frame: 8 weeks
Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes (Percent)
Time Frame: 4 weeks
Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes (Percent)
Time Frame: 8 weeks
Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes (Percent)
Time Frame: 4 weeks
Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Static Lung Volumes (Percent)
Time Frame: 8 weeks
Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)
8 weeks
Static Lung Volumes (Percent)
Time Frame: 4 weeks
Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
4 weeks
Slow Vital Capacity (SVC)
Time Frame: 8 weeks
Trough SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)
8 weeks
Slow Vital Capacity (SVC)
Time Frame: 4 weeks
Trough SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)
4 weeks
Slow Vital Capacity (SVC)
Time Frame: 8 weeks
Post-dose SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)
8 weeks
Slow Vital Capacity (SVC)
Time Frame: 4 weeks
Post-dose SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)
4 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 8 weeks
Trough FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)
8 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 4 weeks
Trough FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)
4 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 8 weeks
Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)
8 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 4 weeks
Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)
4 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 8 weeks
Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)
8 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 4 weeks
Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)
4 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 8 weeks
Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)
8 weeks
Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 4 weeks
Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)
4 weeks
Forced Vital Capacity (FVC)
Time Frame: 8 weeks
Trough FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)
8 weeks
Forced Vital Capacity (FVC)
Time Frame: 4 weeks
Trough FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)
4 weeks
Forced Vital Capacity (FVC)
Time Frame: 8 weeks
Post-dose FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)
8 weeks
Forced Vital Capacity (FVC)
Time Frame: 4 weeks
Post-dose FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)
4 weeks
FEV1 Over FVC (Percent)
Time Frame: 8 weeks
Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)
8 weeks
FEV1 Over FVC (Percent)
Time Frame: 4 weeks
Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)
4 weeks
FEV1 Over FVC (Percent)
Time Frame: 8 weeks
Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)
8 weeks
FEV1 Over FVC (Percent)
Time Frame: 4 weeks
Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)
4 weeks
Symptom Intensity During Exercise
Time Frame: 8 weeks
Isotime Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10), 0 = no dyspnea, 10 = worst imaginable dyspnea
8 weeks
Symptom Intensity During Exercise
Time Frame: 4 weeks
Isotime Borg dyspnea scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no dyspnea, 10 = worst imaginable dyspnea
4 weeks
Symptom Intensity During Exercise
Time Frame: 8 weeks
Isotime Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort
8 weeks
Symptom Intensity During Exercise
Time Frame: 4 weeks
Isotime Borg leg discomfort scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort
4 weeks
Dyspnea and Leg Discomfort
Time Frame: 8 weeks
Peak Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10)
8 weeks
Dyspnea and Leg Discomfort
Time Frame: 8 weeks
Peak Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max 10)
8 weeks
Locus of Symptom Limitation at Peak Exercise During Exercise
Time Frame: baseline
Reason for stopping exercise at baseline (leg discomfort, breathing discomfort, both or none)
baseline
Locus of Symptom Limitation at Peak Exercise During Exercise
Time Frame: 4 weeks
Reason for stopping exercise after 4 weeks (leg discomfort, breathing discomfort, both or none)
4 weeks
Locus of Symptom Limitation at Peak Exercise During Exercise
Time Frame: 8 weeks
Reason for stopping exercise after 8 weeks (leg discomfort, breathing discomfort, both or none)
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

September 17, 2007

First Submitted That Met QC Criteria

September 17, 2007

First Posted (Estimate)

September 18, 2007

Study Record Updates

Last Update Posted (Estimate)

December 24, 2013

Last Update Submitted That Met QC Criteria

November 27, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 205.334

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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