Official Title: “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 Type: Interventional

Study Design: Treatment, Crossover Assignment, Efficacy Study

Study Primary Completion Date: January 2009

Intervention(s) in this Clinical Trial

• Drug: Tiotropium plus Salmeterol
• Drug: Fluticasone/Salmeterol

Primary Measures

• Two coprimary efficacy endpoints are defined: a) Postdose TGV(FRC) b) Endurance time to the point of symptom limitation during a constant work rate exercise test at 75% Wcap
  • Time Frame: Crossover, 2 x 8 weeks
    

Secondary Measures

• Static lung volumes FEV1 and FVC; SVC Symptom intensity during exercise dyspnoea and leg discomfort Locus of symptom limitation at peak exercise during exercise. Safety parameters
  • Time Frame: crossover, 2 x 8 weeks
    

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 COPD.
• 3. The patient has relatively stable, moderate to severe airway obstruction.
• 4. The patient has a pre-bronchodilator FEV1 less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):
• 1. Males FEV1 predicted [L] = 4.30 x Height [metres] minus 0.029 x Age [years] minus 2.49
• 2. Females FEV1 predicted [L] = 3.95 x Height [metres] minus 0.025 x Age [years] minus 2.60 and a TGV(FRC) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
• 3. Males TGV(FRC) pred. [L] = 2.34 x Height [metres] + 0.009 x Age [years] minus 1.09
• 4. Females TGV(FRC) pred. [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 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 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 COPD.
• 26. treatment with MOA inhibitors or tricyclic antidepressants.
• 27. participation in another study.
• 28. more than eight puffs of salbutamol/day during the run-in period

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Boehringer Ingelheim Pharmaceuticals

Overall Clinical Trial Officials and Contacts

Boehringer Ingelheim Study Chair Boehringer Ingelheim Pharmaceuticals  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00530842

Study ID Number: 205.334

ClinicalTrials.gov Identifier: NCT00530842

Health Authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna