To Evaluate the Effect of Inhaled Medication Together With Exercise and Activity Training on Exercise Capacity and Daily Activities in Patients With Chronic Lung Disease With Obstruction of Airways
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: placebo to tiotropium + olodaterol; tiotropium+olodaterol; tiotropium +olodaterol; tiotropium
Intervention description: comparator; tiotropium 5 mcg once daily; olodaterol 5 mcg once daily fixed dose combination; tiotropium 5 mcg once daily fixed dose combination
Intervention MeSH terms: Tiotropium Bromide; Olodaterol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single
Enrollment: 304.0
Sex: All
Minimum age: 40 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The primary objectives of the study are to explore the effect of treatment with orally
      inhaled tiotropium + olodaterol fixed dose combination with and without exercise training,
      and tiotropium comparing to placebo, on top of behavioural modification in improving exercise
      capacity in patients with COPD
    

Eligibility criteria:

        Inclusion criteria:

          -  All patients must sign an informed consent consistent with International Conference on
             Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human
             Use (ICH) - Good Clinical Practice (GCP) guidelines prior to participation in the
             trial, which includes medication washout and restrictions.

          -  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 forced expiratory volume in one second >=30%
             and <80% of predicted normal; Global Initiative for Chronic Obstructive Lung Disease
             grade II - III, and a post-bronchodilator Tiffeneau index <70% at Visit 1.

          -  Male or female patients, aged >=40 years and <=75 years.

          -  Patients must be current or ex-smokers with a smoking history of more than 10 pack
             years. Patients who have never smoked cigarettes must be excluded.

        Exclusion criteria:

          -  Patients with a significant disease other than chronic obstructive pulmonary disease.

          -  Patients with clinically relevant abnormal baseline haematology, blood chemistry, or
             urinalysis.

          -  Patients with a history of asthma.

          -  A diagnosis of thyrotoxicosis.

          -  A diagnosis of paroxysmal tachycardia (>100 beats per minute).

          -  A history of myocardial infarction within 1 year of screening visit.

          -  Unstable or life-threatening cardiac arrhythmia.

          -  Hospitalized for heart failure within the past year.

          -  Known active tuberculosis.

          -  A malignancy for which patient has undergone resection, radiation therapy or
             chemotherapy within last five years.

          -  A history of life-threatening pulmonary obstruction and patients with chronic
             respiratory failure.

          -  A history of cystic fibrosis.

          -  Clinically evident bronchiectasis.

          -  A history of significant alcohol or drug abuse.

          -  Any contraindications for exercise testing.

          -  Patients who have undergone thoracotomy with pulmonary resection.

          -  Patients being treated with any oral ß-adrenergics.

          -  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 investigators opinion will be unable to abstain from the use of oxygen therapy
             during clinic visits.

          -  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 dyspnoea, such as arthritis in the leg, angina pectoris or
             claudication or morbid obesity.

          -  Patients who have taken an investigational drug within one month or six half lives
             (whichever is greater) prior to screening visit.

          -  Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs,
             benzalkonium chloride, disodium edentat, or any other component of the Respimat®
             inhalation solution delivery system.

          -  Pregnant or nursing women.

          -  Women of childbearing potential not using highly effective methods of birth control.

          -  Patients who have previously been randomized in this study or are currently
             participating in another study.