The Effect of STIOLTO™ RESPIMAT® on Fatigue in Chronic Obstructive Pulmonary Disease
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Stiolto Respimat; Placebo Respimat
Intervention description: Oral inhalation spray; Oral inhalation spray
Intervention MeSH terms: Bromides; Tiotropium Bromide; Olodaterol
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 14.0
Sex: All
Minimum age: 45 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether exercise can be prolonged in COPD can by
      the inhaled bronchodilator Stiolto Respimat. The study will identify whether any endurance
      benefit is due to reduction in fatigue that originates within the skeletal muscles and/or
      from effects on neural activation of the skeletal muscles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have a diagnosis of chronic obstructive pulmonary disease and must
             meet the following criteria: (a) Patients must be in a stable state of their disease
             with no exacerbation within the previous 4 weeks; and (b) At visit 1 spirometric must
             demonstrate a post-bronchodilator FEV1 <80% of predicted normal and a
             post-bronchodilator FEV1/FVC <70%.

          -  At visit 1, patients will demonstrate appreciable reversibility, defined as a 12%
             increase in FEV1 in response to albuterol administration.

          -  Baseline dyspnea index focal score ≤ 9.

          -  Male or female patients, between 45 and 90 years (inclusive) of age.

          -  Patients must be current or ex-smokers with a smoking history of more than 10
             pack-years

          -  Patients must be able to perform technically acceptable pulmonary function tests must
             be able to complete multiple symptom-limited cycle ergometry tests.

          -  Patients must be able to inhale medication in a competent manner from the inhalers
             used in the study.

        Exclusion Criteria:

          -  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.

          -  Patients with a documented history of asthma. For patients with allergic rhinitis or
             atopy, medical records will be required to verify that the patient does not have
             asthma.

          -  Patients with any of the following conditions:

               1. A history of myocardial infarction within 1 year of screening visit.

               2. Unstable or life-threatening cardiac arrhythmia.

               3. Hospitalized for heart failure within the past year.

               4. Known active tuberculosis.

               5. A malignancy for which patient has undergone resection, radiation therapy or
                  chemotherapy within last two years (patients with treated basal cell carcinoma
                  are allowed).

               6. A history of life-threatening pulmonary obstruction within the past two years.

               7. A history of cystic fibrosis.

               8. Clinically evident bronchiectasis.

               9. A history of significant alcohol or drug abuse within the past two years.

              10. Any contraindications for exercise testing as outlined below (see
                  contraindications to exercise).

              11. Patients who have undergone thoracotomy with pulmonary resection.

          -  Patients being treated with oral corticosteroid medication at unstable doses (i.e.,
             less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg
             of prednisone per day or 20 mg every other day.

          -  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.

          -  Patients who desaturate to SpO2 <85% on screening incremental exercise testing.

          -  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.

          -  Patients who have a limitation of exercise performance as a result of factors other
             than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris or
             claudication or morbid obesity.

          -  Patients with a constant power cycle ergometry endurance time less than 4 or greater
             than 10 minutes after work rate adjustment procedures (described below).

          -  Patients who have taken an investigational drug within one month or six half-lives
             (whichever is greater) prior to screening visit (Visit 1).

          -  Pregnant or nursing women.

          -  Women of childbearing who have the potential not to be using a highly effective method
             of birth control. Female patients will be considered to be of childbearing potential
             unless surgically sterilized by hysterectomy or bilateral tubal ligation, or
             post-menopausal for at least two years.

          -  Patients who are currently participating in another interventional study.

          -  Patients who are unable to comply with pulmonary medication restrictions prior to
             randomization.