Effect of Tiotropium + Olodaterol on Breathlessness in COPD Patients

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive Read More

Inclusion criteria:

• Patients must sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice guidelines prior to participation in the trial, including medication washout and restrictions
• Diagnosis of Chronic Obstructive Pulmonary Disease and relatively stable airway obstruction: post bronchodilator 30%<= Forced Expiratory Volume in 1st second (FEV1)<80% of predicted normal (European Coal and Steel Community) and a post bronchodilator FEV1/Forced Vital Capacity<0.70 at visit 1
• Male or female patients >=40 and =<75 years of age on day of signing consent.
• Current or ex-smokers with a smoking history > 10 pack-years. Patients who have never smoked cigarettes must be excluded.
• Baseline Dyspnea Index score< 8 at visit 0.
• Hyperinflation at rest, defined as Functional Residual Capacity > 120% predicted at visit 1.
• Borg dyspnea score >=4 at the end of 3min Constant Speed Shuttle Test at visit 2
• Perform technically acceptable pulmonary function tests (spirometry and body plethysmography) and complete multiple shuttle tests during the study period
• Inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler

Exclusion criteria:

• Significant disease other than Chronic Obstructive Pulmonary Disease (COPD); a significant disease which, in the investigator's opinion, may (i) put the patient at risk (ii) influence the study results or (iii) cause concern regarding the patient's ability to participate
• Clinically relevant abnormal baseline haematology, blood chemistry, in the investigator's opinion, or creatinine >x2 Upper Limit Normal will be excluded regardless of clinical condition
• Current documented diagnosis of asthma
• COPD exacerbation in the 6 weeks prior to screening
• Diagnosis of thyrotoxicosis
• History of myocardial infarction within 6 months of screening
• Life-threatening cardiac arrhythmia (investigator judgment)
• Known active tuberculosis
• Any malignancy unless free of disease for at least 5 years (treated basal cell carcinoma or squamous cell skin cancers are allowed)
• History of cystic fibrosis
• Clinically relevant bronchiectasis (investigator judgment)
• Severe emphysema requiring endobronchial interventions within 6 months prior to screening
• History of significant alcohol or drug abuse (investigator judgment)
• Any contraindications for exercise testing
• Patients who have undergone thoracotomy with pulmonary resection
• Treatment with any oral or patch ß-adrenergics
• Treatment with oral corticosteroid medication at unstable doses or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day
• Treatment with antibiotics for any reason within 4 weeks of screening
• Patients being treated with Phosphodiesterase Type 4 (PDE4) inhibitors within 3 months of screening visit should not be enrolled and PDE4 inhibitors should not be withdrawn for the purpose of enrolling in this study
• Regular use of daytime oxygen therapy for >1 hour per day and in the investigator's opinion will be unable to abstain from use during clinic visits
• Completion of a pulmonary rehabilitation program 6 weeks prior to screening or currently in a program
• Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris, claudication, morbid obesity
• Endurance time >=12 minutes during the incremental shuttle walk test
• Oxygen saturation < 85% (on room air) at rest or during exercise.
• Taken an investigational drug within 1 month or 6 half-lives or in case the investigational drug class is listed within the washout period specified prior to screening visit
• Known hypersensitivity to ß-adrenergics and/or anticholinergic drugs, Benzalkonium Chloride, Ethylenediaminetetraacetic acid or any other component of the Respimat® inhalation solution
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial
• Women of childbearing potential not using a highly effective method of birth control
• Previously been randomized in this study or are currently participating in another study
• Unable to comply with pulmonary medication restrictions prior to randomization