A Study to Compare the Impact of Fulticasone Furoate/Vilanterol vs. Tiotropium on Arterial Stiffness in COPD
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is designed to evaluate the effect of fluticasone furoate (FF,
      GW685698)/vilanterol (VI, GW642444) Inhalation Powder once daily (QD) on arterial stiffness
      compared with Tiotropium QD over 12 week treatment period in subjects with COPD and aortic
      pulse wave velocity (aPWV) > 12.0 m/s at Visit 1. Arterial stiffness will be measured as
      aPWV. This is a comparator, randomised, double-blind, double-dummy, parallel group,
      multi-centre study. Subjects who meet the eligibility criteria at Screening and meet the
      randomization criteria at the end of a 2-week Run-In period will enter a 12-week treatment
      period. There will be an approximate 7-day Follow-up period after the treatment period.
    

Detailed description: 
      This is a Phase IIIb comparator, double-blind, double-dummy, randomised (1:1), parallel
      group, multi-centre study. At Visit 1 (Screening Visit), subjects who meet the pre-defined
      Inclusion Criteria and none of the Exclusion Criteria will enter a 2-week, single-blind
      placebo Run-in Period. The purpose of the Run-In Period is to monitor albuterol/salbutamol
      use at baseline, and to ensure that subjects' COPD is at a stable stage at randomization.
      Subject's adherence with study procedures, diary completion will also be evaluated during the
      Run-In Period. At the end of the Run-in period, subjects will be assessed and those who meet
      the randomisation criteria will receive one of the following two double-blind treatments for
      12 weeks:

        -  FF (100 mcg)/VI (25 mcg) administered QD via a NDPI in the morning

        -  Tiotropium (18 mcg) administered QD via a HandiHaler in the morning

      To ensure blinding of the treatments and to ensure a double-dummy design matching NDPI and
      HandiHaler will be utilised. Each subject will be instructed to self administer blinded study
      drug during the double blind treatment period as follows:

        -  Each morning take 1 inhalation from NDPI containing FF (100 mcg)/VI (25 mcg) followed by
           1 inhalation from placebo capsule delivered via HandiHaler.

        -  Each morning take 1 inhalation from matching placebo NDPI followed by 1 inhalation from
           a capsule containing tiotropium 18 mcg delivered via HandiHaler.

      An inhaled short acting beta2-receptor agonist, salbutamol/albuterol will be provided to
      subjects to use as needed throughout the Run-in and Treatment periods for relief of COPD
      symptoms. Ipratropium bromide is permitted if the subject is on a stable dose from Screening
      (Visit 1) and remains on the stable dose throughout the study. Subjects who experience an
      exacerbation of their COPD (which requires medication in addition to an increase in rescue
      medication) or a lower respiratory tract infection (LRTI) during the run-in period are not
      eligible to enter the treatment period. Any subject who experiences a similar COPD
      exacerbation (sec 4.4) or LRTI at any time on therapy will be withdrawn from the study. The
      aPWV will be measured at Screening and clinic Visits 3-5. Disease specific health status will
      be evaluated using the St. George's Respiratory Questionnaire (SGRQ-C), Euro Qol
      Questionnaire (EQ-5D) for COPD patients and the COPD Assessment Test (CAT) at Visit 2 (Day 1)
      and at Visit 5 (Weeks 12). The 12-lead ECG will be evaluated at Visit 1 (Screening) only.
      Vital signs (blood pressure and pulse rate), spirometry measurements, and clinical laboratory
      tests (hematology and chemistry) and other study-specific safety assessments will be obtained
      at selected clinic visits. A follow-up phone call will occur approximately 7 days after the
      last clinic visit. The overall study duration from Screening to Follow-up for each subject is
      approximately 15 weeks. Subjects will be considered to have completed the study upon
      completion of assessments and procedures up to and including completion of Follow-up Phone
      Contact (7 ± 2 days post Visit 5).
    

Intervention name(s): fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Novel Dry Powder Inhaler (NDPI); Tiotropium
Intervention type(s): Drug; Drug
Intervention description(s): fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Inhalation Powder delivered once daily via a Novel Dry Powder Inhaler (NDPI); • Tiotropium (18 mcg) administered QD via a HandiHaler
Intervention MeSH terms: Fluticasone; Xhance; Tiotropium Bromide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment