Study to Evaluate the Efficacy and Safety of Glycopyrronium or Indacaterol Maleate and Glycopyrronium Bromide Fixed-dose Combination Regarding Symptoms and Health Status in Patients With Moderate COPD Switching From Treatment With Any Standard COPD Regimen
Condition: COPD
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: Glycopyrronium; SABA; LABA; Indacaterol maleate and glycopyrronium bromide; LAMA; SAMA; ICS
Intervention description: Glycopyrronium 50 µg capsule for inhalation via SDDPI once per day; Short-acting β2-adrenergic agonist (SABA) as per approved by each country and as prescribed for each patient, used as background therapy; Long Acting Beta Agonist (LABA) as per approved by each country and as prescribed for each patient, used as background therapy; Indacaterol maleate and glycopyrronium bromide fixed dose combination (110/50 µg) capsule for inhalation via SDDPI, once a day; Long Acting Muscarinic Antagonist (LAMA) as per approved by each country and as prescribed for each patient, used as background therapy; Short-acting muscarinic antagonist (SAMA) as per approved by each country and as prescribed for each patient, used as background therapy; Inhaled corticosteroid (ICS) as per approved by each country and as prescribed for each patient, used as background therapy
Intervention MeSH terms: Glycopyrrolate; Bromides
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4389.0
Sex: All
Minimum age: 40 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Moderate COPD, glycopyrronium bromide, indacaterol maleate and glycopyrronium bromide FDC, NVA237, QVA149

Summary:

      The main goal of this study is to evaluate the efficacy and safety of glycopyrronium bromide
      and indacaterol maleate and glycopyrronium bromide fixed dose combination (FDC) in patients
      with moderate COPD who switch from their current COPD therapy. This study aims to provide
      data on how non-exacerbating, but still symptomatic patients with moderate COPD switching
      from their current COPD treatment to glycopyrronium bromide or indacaterol maleate and
      glycopyrronium bromide FDC maintain or improve their symptoms. Another purpose of this study
      is to increase awareness and usage of validated COPD symptoms tools and dyspnea
      questionnaires in order to facilitate clinical assessment and improve early diagnosis of
      symptomatic patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female adults aged ≥ 40 years

          -  Patients with moderate COPD according to the GOLD criteria 2013

          -  Current or ex-smokers who have a smoking history of at least 10 pack years

          -  Patients with airflow limitation indicated by a postbronchodilator FEV1 ≥50% and <80%
             of the predicted normal value and a post-bronchodilator FEV1/FVC <0.7 at Visit 2.
             Post- bronchodilator refers to within 10-15 min of inhalation of 400 μg (4x100 μg) of
             salbutamol

          -  Patients who, at Visit 1, have been for at least 3 months on a stable dose of one of
             the following COPD baseline treatments: *Any SABA monotherapy (such as, but not
             limited to, salbutamol) *Any SAMA monotherapy (such as, but not limited to,
             ipratropium) *Any SABA and SAMA in free or FDC (such as, but not limited to,
             salbutamol/ipratropium) *Any LABA monotherapy (such as, but not limited to,
             formoterol, salmeterol, indacaterol) *Any LAMA monotherapy (such as, but not limited
             to, tiotropium, aclidinium) except glycopyrronium bromide (NVA237) *Any LABA and ICS
             in free (ICS such as, but not limited to, beclomethasone, fluticasone) or FDC (such
             as, but not limited to, salmeterol/fluticasone, formoterol/budesonide).

          -  Patients with an mMRC score ≥1 at Visit 1.

        Exclusion Criteria:

          -  Patients with conditions contraindicated for treatment with, or having a history of
             reactions/ hypersensitivity to any of the following inhaled drugs or to drugs of
             similar chemical classes or any component thereof: Anti-cholinergic agents, Long- and
             short-acting 2-adrenergic agonists, Sympathomimetic amines, Lactose or any of the
             other excipients of the trial medication.

          -  Patients with narrow-angle glaucoma or urinary retention, severe renal impairment
             (history of estimated glomerular filtration rate below 30 ml/min/1.73 m2 within 12
             months prior to visit 1), including those with end-stage renal disease requiring
             dialysis.

          -  Patients with active/ clinical history of asthma.If the Investigator finds clear and
             compelling evidence that a patient was misdiagnosed with asthma in the past, then the
             burden of proof is on the Investigator to properly document this previous
             misdiagnosis. This documentation must include the rationale for this change in
             diagnosis including reference to the differential diagnosis that supports this
             decision.

          -  Patients with a history of malignancy of any organ system (other than localized basal
             cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless
             of whether there is evidence of local recurrence or metastases.

          -  Patients who have a post-bronchodilator FEV1 decrease more than 10% compared to
             pre-bronchodilator FEV1 result at Visit 2 (see Appendix 5 for details).

          -  A documented history of >1 COPD exacerbation requiring treatment with systemic
             corticosteroids or antibiotics and/or hospitalization in the previous 12 months.

          -  Patients who have NOT had a COPD exacerbation in the previous 12 months and develop a
             COPD exacerbation between screening (Visit 1) and (Visit 2) will not be eligible but
             will be permitted to be re-screened after a minimum of 6 weeks after the resolution of
             the COPD exacerbation. (Patients suffering an exacerbation between Visit 1 and Visit 2
             can only be re-screened in case it is the first one in the previous 12 months. In case
             this COPD exacerbation has led to an alteration of the patient COPD treatment, before
             this patient can be re-screened 3 months of stable COPD treatment will be required as
             described in Inclusion Criterion 6).

          -  Patients who, in the judgment of the investigator, have a clinically relevant
             laboratory abnormality or a clinically significant condition such as (but not limited
             to): *Unstable ischemic heart disease, left ventricular failure (NYHA Class III & IV),
             history of myocardial infarction,arrhythmia (excluding chronic stable atrial
             fibrillation). Patients with such events not considered clinically significant by the
             investigator may be considered for inclusion in the study.*Uncontrolled hypo-or
             hyperthyroidism, hypokalaemia or hyperadrenergic state. *Any condition which might
             compromise patient safety or compliance, interfere with evaluation, or preclude
             completion of the study

          -  History of resting QTc (Fridericia preferred, but Bazett acceptable) >450 msec (male)
             or >460 msec (female) within five years before Visit 1.

          -  Patients who are treated with glycopyrronium bromide (NVA237) at visit 1 are not
             allowed to be included into the trialPatients on non-selective beta-blockers. Those
             patients may enter the study after non-selective beta-blocker withdrawal during a
             7-day wash-out period.

          -  Patients receiving any other prohibited COPD-related medications specified in Table
             5-2 Prohibited COPD related medications must undergo the required wash-out period
             prior to Visit 2.

          -  Patients who are, in the opinion of the investigator known to be unreliable or
             non-compliant.

          -  Patients with a body mass index (BMI) of more than 40 kg/m2.

          -  Use of other investigational drugs within 5 half-lives of enrollment or within 30
             days, whichever is longer.

          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test.

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using effective methods of contraception during
             dosing of study treatment.