The ENERGITO® 2 Study Compares 2 Inhaled Medicines for Chronic Obstructive Pulmonary Disease (COPD). One Medicine is a Combination of Tiotropium and Olodaterol (Stiolto®) Taken Using the Respimat® Inhaler and the Other Medicine is a Combination of Fluticasone and Salmeterol Taken Using the Diskus
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Tiotropium; Olodaterol; Fluticasone propionate; Salmeterol
Intervention description: Fixed Dose Combination; Fixed Dose Combination; Fixed Dose Combination; Fixed Dose Combination
Intervention MeSH terms: Fluticasone; Xhance; Tiotropium Bromide; Salmeterol Xinafoate; Olodaterol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 302.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      The primary objective of the trial is to show superiority in lung function of once daily (2
      inhalations) treatment with orally inhaled tiotropium+olodaterol fixed dose combination to
      twice daily (one inhalation) treatment with fluticasone propionate+salmeterol fixed dose
      combination over 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD).

      A Digital Health (DH) exploratory study has been integrated into the main study as a site
      specific study. The DH exploratory study will be performed at a single site; the site is also
      participating in the main study. The DH exploratory study site will enter (randomize)
      approximately 20 patients (subjects) (in addition to the patients to be enrolled in the main
      study at this site). The patients enrolled in the DH exploratory study are not considered to
      be part of the main study (i.e. data collected in the DH exploratory study will be analyzed
      separately from the data collected in the main study).
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must sign an informed consent consistent with FDA regulations 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 with a post-bronchodilator 30% ≤ Forced Expiratory Volume in one second
             (FEV1) <80% of predicted normal (European Coal and Steel Community( ECSC)); and a
             post-bronchodilator FEV1/Forced Vital Capacity (FVC) <70% at Visit 1

          -  Male or female patients, 40 years of age or older.

          -  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.

          -  Patients must be able to perform, according to investigator's judgment, all trial
             related procedures including:

               -  Technically acceptable pulmonary function tests (spirometry)

               -  Completion of study questionnaires

          -  Patients must be able to inhale medication in a competent manner (in the opinion of
             the investigator) from the Respimat® and Diskus® inhalers and from a metered dose
             inhaler (MDI).

        Exclusion Criteria:

          -  Patients with a significant disease other than Chronic Obstructive Pulmonary Disease
             (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 who have had a COPD exacerbation that required treatment with antibiotics,
             systemic steroids (oral or intravenous) or hospitalization in the last 3 months prior
             to Visit 1 and/or between Visit 1 and Visit 2.

          -  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. If a
             patient has a total blood eosinophil count ≥ 600/mm3, source documentation is required
             to verify that the increased eosinophil count is related to a nonasthmatic condition.

        Patients with any of the following conditions:

          -  A diagnosis of thyrotoxicosis (due to the known class side effect profile of
             ß2-agonists).

          -  A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class
             side effect profile of ß2-agonists).

          -  A history of myocardial infarction within 1 year of screening visit (Visit 1).

          -  Unstable or life-threatening cardiac arrhythmia.

          -  Hospitalization 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 (patients with treated basal cell carcinoma are
             allowed).

          -  A history of life-threatening pulmonary obstruction.

          -  A history of cystic fibrosis.

          -  Clinically evident bronchiectasis.

          -  A history of significant alcohol or drug abuse.

          -  Patients who have undergone thoracotomy with pulmonary resection (patients with a
             history of thoracotomy for other reasons should be evaluated as per the first
             exclusion criterion).

          -  Patients being treated with oral or patch β-adrenergics.

          -  Patients being treated with oral corticosteroid medication within 6 weeks prior to
             Visit 1.

          -  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 have completed a pulmonary rehabilitation program in the six weeks prior
             to the screening visit (Visit 1) or patients who are currently in a pulmonary
             rehabilitation program.

          -  Patients who have taken an investigational drug within one month, six half-lives or
             within the wash out period (whichever is greater) prior to screening visit (Visit 1).

          -  Patients with known hypersensitivity to β-adrenergic drugs, BAC, EDTA, or any other
             component of the Respimat® inhalation solution. In addition, patients with known
             hypersensitivity to Lactose monohydrate (which contains milk proteins).

          -  Pregnant or nursing women.

          -  Women of childbearing potential not using a method of birth control classified at
             least as "acceptable". Female patients will be considered to be of childbearing
             potential unless surgically sterilized by hysterectomy, bilateral salpingectomy,
             bilateral oophorectomy, or post-menopausal (defined as no menses for 12 months without
             an alternative medical cause). Tubal ligation is NOT a method of permanent
             sterilisation.

          -  Patients who have previously been randomized in this study or are currently
             participating in another study.

          -  Patients who are unable to comply with pulmonary medication restrictions prior to
             randomization.