A 52-Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety and Tolerability of GSK573719/GW642444 and GSK573719 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: 125/25 mcg once-daily GSK573719/GW642444; 125mcg once-daily GSK573719; Placebo once-daily
Intervention description: GSK573719/GW642444; GSK573719; inactive
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 563.0
Sex: All
Minimum age: 40 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Pulmonary Disease; COPD; nDPI; long-acting beta agonist; long-acting muscarinic antagonist; tolerability; safety

Summary:

      The purpose of this 52-week study is to evaluate the long-term safety (in terms of adverse
      events, COPD exacerbations, laboratory, ECG, and Holter findings, vital signs, use of rescue
      medication and lung function) of GSK573719/GW642444 Inhalation Powder 125/25mcg in subjects
      with COPD. The long-term safety of GSK573719 Inhalation Powder 125mcg will also be evaluated.
      A placebo arm is included to evaluate these products compared to an inactive control.
    

Eligibility criteria:

        Inclusion Criteria:

          -  outpatient

          -  signed and dated written informed consent

          -  40 years of age or older

          -  male and female subjects

          -  COPD diagnosis

          -  at least 10 pack-year smoking history

          -  post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and post-albuterol/salbutamol FEV1
             greater than or equal to 35% and less than or equal to 80% of predicted normal

        Exclusion Criteria:

          -  Pregant or lactating women or women planning to become pregnant during the study

          -  current diagnosis of asthma

          -  other respiratory disorders other than COPD

          -  other diseases/abnormalities that are uncontrolled including cancer not in remission
             for at least 5 years

          -  chest x-ray or CT scan with clinically significant abnormalities not believed to be
             due to COPD

          -  hypersensitivity to anticholinergics, beta-agonists, lactose/milk protein or magnesium
             stearate or medical conditions associated with inhaled anticholinergics

          -  hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1

          -  lung volume reduction surgery within 12 months prior to Visit 1

          -  abnormal and clinically significant ECG at Visit 1

          -  abnormal and clinically significant Holter monitor finding at Visit 1

          -  significantly abnormal finding from laboratory tests at Visit 1

          -  unable to withhold albuterol/salbutamol and/or ipratropium bromide at least 4 hours
             prior to spirometry at each visit

          -  use of depot corticosteroids within 12 weeks of Visit 1

          -  use of oral or parenteral corticosteroids within 6 weeks of Visit 1

          -  use of anitbiotics for lower respiratory tract infection within 6 weeks of Visit 1

          -  use of cytochrome P450 3A4 inhibitors within 6 weeks of Visit 1

          -  us of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) products if
             LABA/ICS therapy is discontinued completely within 30 days of Visit 1

          -  use of ICS at a dose of >10000mcg/day of fluticasone propionate or equivalent within
             30 days of Visit 1

          -  initiation or discontinuation of ICS within 30 days of Visit 1

          -  use of tiotropium within 14 days of Visit 1

          -  use of roflumilast within 14 days of Visit 1

          -  use of theophyllines within 48 hours of Visit 1

          -  use of oral leukotriene inhibitors within 48 hours prior to Visit 1

          -  use of long-acting oral beta-agonists within 48 hours of Visit 1

          -  use of short-acting oral beta-agonists within 12 hours of Visit 1

          -  use of inhaled long-acting beta-agonists within 48 hours prior to Visit 1

          -  use of LABA/ICS combination products only if discontinuing LABA therapy and switching
             to ICS monotherapy within 48 hours of Visit 1 for the LABA component

          -  use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1

          -  use of inhaled short acting beta-agonists within 4 hours of Visit 1

          -  use of inhaled short-acting anticholinergics within 4 hours of Visit 1

          -  use of inhaled short-acting anticholinergic/short-acting beta2-agonist combination
             products within 4 hours of Visit 1

          -  use of any other investigational medication within 30 days or 5 drug half-lives
             (whichever is longer) of Visit 1

          -  long-term oxygen therapy prescribed for >12 hours per day

          -  regular use of short-acting bronchodilators

          -  use of CPAP or NIPPV

          -  participation in the maintenance phase of a pulmonary rehabilitation program

          -  known or suspected history of alcohol or drug abluse with 2 years prior to Visit 1

          -  anyone affiliated with the investigator site (e.g., investigator, study coordinator,
             etc.)

          -  previous use of GSK573719, GW642444 , GSK573719/GW642444 combination,
             GSK233705/GW642444 combination, or Fluticasone Furoate/GW642444 combination