Effect of Tiotropium + Olodaterol on Breathlessness in COPD Patients
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive; Dyspnea
Intervention: Tiotropium; Olodaterol; Tiotropium
Intervention description: fixed dose combination once daily; fixed dose combination once daily
Intervention MeSH terms: Tiotropium Bromide; Olodaterol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 106.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The primary objective of the present study is to evaluate the effect of tiotropium +
      olodaterol fixed dose combination (FDC) compared to tiotropium monotherapy on the intensity
      of breathlessness during the 3min constant speed shuttle test (CSST).

      A secondary objective is to explore the relationship between reductions in breathlessness
      during the 3min CSST and reductions in breathlessness during activities of everyday living as
      measured by the dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) following
      bronchodilator therapy.
    

Eligibility criteria:

        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