Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients.
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: Placebo; Tiotropium + Olodaterol; tiotropium + Olodaterol; Tiotropium; Olodaterol; Respimat
Intervention description: placebo matching tiotropium + olodaterol; Tiotropium 2.5 mcg + olodaterol 5 mcg once daily; tiotropium 5 mcg + olodaterol 5 mcg once daily; tiotropium; Olodaterol 5 mcg once daily; Respimat inhaler
Intervention MeSH terms: Tiotropium Bromide; Olodaterol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 291.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The primary objective of this trial is to investigate the effect of 6 weeks treatment with
      tiotropium + olodaterol fixed dose combination inhalation solution on lung hyperinflation and
      exercise tolerance in patients with COPD.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to
             participation in the trial, which includes medication washout and restrictions.

          2. 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 a post-bronchodilator
             FEV1 <80% of predicted normal and a post-bronchodilator FEV1/FVC <70% at Visit 1.

          3. Male or female patients, between 40 and 75 years of age (inclusive) on day of signing
             informed consent.

          4. Patients must be current or ex-smokers with a smoking history of more than 10 pack
             years.

        Exclusion criteria:

          1. Patients with a significant disease other than COPD; a significant disease is defined
             as a disease which, in the opinion of the investigator, may (i) put the patient at
             risk because of participation in the study, (ii) influence the results of the study,
             or (iii) cause concern regarding the patient's ability to participate in the study

          2. 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

          3. Patients with a history of asthma. For patients with allergic rhinitis or atopy,
             source documentation is required to verify that the patient does not have asthma.

             Patients with any of the following conditions:

          4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of
             ß2-agonists)

          5. A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class
             side effect profile of ß2-agonists)

          6. A history of myocardial infarction within 1 year of screening visit (Visit 1)

          7. Unstable or life-threatening cardiac arrhythmia

          8. Hospitalized for heart failure within the past year

          9. Known active tuberculosis

         10. A malignancy for which patient has undergone resection, radiation therapy or
             chemotherapy within last five years (patients with treated basal cell carcinoma are
             allowed)

         11. A history of life-threatening pulmonary obstruction

         12. A history of cystic fibrosis

         13. Clinically evident bronchiectasis

         14. A history of significant alcohol or drug abuse

         15. Any contraindications for exercise testing.

         16. Patients who have undergone thoracotomy with pulmonary resection (patients with a
             history of thoracotomy for other reasons should be evaluated as per exclusion
             criterion No. 1)

         17. Patients being treated with any oral ß-adrenergics

         18. Patients being treated with oral corticosteroid medication at unstable doses

         19. Patients who regularly use daytime oxygen therapy for more than one hour per day and
             in the investigator's opinion will be unable to abstain from the use of oxygen therapy
             during clinic visits

         20. Patients who have completed a pulmonary rehabilitation program in the six weeks prior
             to the screening visit or patients who are currently in a pulmonary rehabilitation
             program

         21. Patients who have a limitation of exercise performance as a result of factors other
             than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or
             claudication or morbid obesity.

         22. Patients who have taken an investigational drug within one month or six half lives
             (whichever is greater) prior to screening visit

         23. Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs,
             BAC, EDTA or any other component of the Respimat® inhalation solution delivery system

         24. Pregnant or nursing women

         25. Women of childbearing potential not using highly effective methods of birth control.