24-week Trial Comparing GSK573719/GW642444 With GSK573719 and With Tiotropium in Chronic Obstructive Pulmonary Disease
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: GSK573719/GW642444 125/25; GSK573719/GW642444 62.5/25; GSK573719; tiotropium bromide
Intervention description: 125/25 mcg once-daily; 62.5/25 mcg once-daily; 125 mcg once-daily; 18 mcg once-daily
Intervention MeSH terms: Bromides; Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 872.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: tiotropium; long-acting muscarinic antagonist; COPD; long-acting beta agonist

Summary:

      This is a Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study
      to evaluate the efficacy and safety of two doses of GSK573719/GW642444 Inhalation Powder,
      GSK573719 Inhalation Powder via a Novel Dry Powder Inhaler and tiotropium via HandiHaler when
      administered once-daily over a 24-week treatment period in subjects with chronic obstructive
      pulmonary disease (COPD). Subjects who meet eligibility criteria at Screening (Visit 1) will
      complete a 7 to10 day run-in period followed by a randomization visit (Visit 2) then a
      24-week treatment period. There will be a total of 9 clinic study visits. A follow-up phone
      contact for adverse event assessment will be conducted approximately one week after the last
      study visit (Visit 9 or Early Withdrawal). The total duration of subject participation in the
      study will be approximately 26 weeks. The primary measure of efficacy is clinic visit trough
      (pre-bronchodilator and pre-dose) forced expiratory volume in one second (FEV1) on Treatment
      Day 169. Safety will be assessed by adverse events, 12-lead ECGs, vital signs, and clinical
      laboratory tests.
    

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
             of less than or equal to 70% predicted normal values

          -  score of greater than or equal to 2 on the Modified Medical Resarch Council Dyspnea
             Scale (mMRC)

        Exclusion Criteria:

          -  women who are pregnant or lactating or are planning on becoming 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

          -  significantly abnormal finding from laboratory tests at Visit 1

          -  unable to withhold albuterol/salbutamol 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, antibiotics for lower respiratory tract
             infection, or cytochrome P450 3A4 inhibitors, within 6 weeks of Visit 1

          -  use of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) product if
             LABA/ICS therapy is discontinued withing 30 days of Visit 1

          -  use of ICS at a dose of >1000mcg/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 or roflumilast within 14 days of Visit 1

          -  use of theophyllines, oral leukotriene inhibitors, long-acting oral beta-agonists, or
             inhaled long-acting beta-agonists within 48 hours of Visit 1

          -  short-acting oral beta-agonists within 12 hours of 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, inhaled short-acting anticholinergics, or
             inhaled short-acting anticholinergic/short-acting beta-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)

          -  long-term oxygen therapy prescribed for >12 hours per day

          -  regular use of nebulized short-acting bronchodilators

          -  participation in acute phase of pulmonary rehabilitation program

          -  known or suspected history of alcohol or drug abse within 2 years prior to Visit 1

          -  anyone affiliated with the investigator site (e.g., investigator, sub-investigator,
             study coordinator, employee of a participating investigator or study site, or
             immediate family member)

          -  previous exposure to GSK573719, GSK573719/GW642444 combination, GW642444 (vilanterol),
             or fluticasone furoate/GW642444 combination