Study Evaluating the 24-Hour Pulmonary Function Profile of Fluticasone Furoate (FF) /GW642444 (Vilanterol) (VI) Inhalation Powder 100/25mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of FF/VI 100/25mcg once daily compared with Fluticasone Propionate/Salmeterol 250/50mcg twice daily over a 12-week treatment period in subjects with COPD.

Detailed Description
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This is a randomized, double-blind, double-dummy, multi-centre parallel group 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 a 7-day Follow-up period after the treatment period.

Official Title
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A 12-week Study to Evaluate the 24-hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg
* Drug: Fluticasone Propionate 250mcg / salmeterol 50mcg
* Drug: Double-dummy placebo
* Drug: Salbutamol as needed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent Male or females ≥ 40 years of age Established clinical history of COPD by ATS/ERS definition Females are eligible to enter and participate if of non-childbearing potential, or if of child bearing potential, has a negative serum pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in protocol, used consistently and correctly Former or current smoker > 10 pack years Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≤ 70% of predicted normal (NHANES III) Exclusion Criteria: Current diagnosis of asthma Subjects with other respiratory disorders including active tuberculosis, α1-antitrypsin deficiency, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases Lung volume reduction surgery within previous 12 months Clinically significant abnormalities not due to COPD by chest x-ray Hospitalized for poorly controlled COPD within 12 weeks of Screening Poorly controlled COPD 6 weeks prior to Screening, defined as acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician Lower respiratory infection requiring antibiotics 6 weeks prior to Screening Uncontrolled or clinically significant (in opinion of PI) cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine, peptic ulcer disease, or hematological abnormalities Carcinoma not in complete remission for at least 5 years Subjects with history of hypersensitivity to study medications (e.g., beta-agonists, corticosteroid) or components of inhalation powder (e.g., lactose, magnesium stearate) Subjects with history of severe milk protein allergy that, in opinion of study physician, contraindicates subject's participation Known/suspected history of alcohol or drug abuse in the last 2 years Women who are pregnant or lactating or plan to become pregnant Subjects medically unable to withhold albuterol and/or ipratropium 4 hours prior to spirometry testing at each study visit Use of certain medications such as bronchodilators and corticosteroids for the protocol-specific times prior to Visit 1 (the Investigator will discuss the specific medications) Long Term Oxygen Therapy (LTOT) or nocturnal oxygen therapy >12 hours a day Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or during the study Non-compliance or inability to comply with study procedures or scheduled visits Affiliation with investigator site

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone Furoate / GW642444 (vilanterol)<br>Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA) | Drug: Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg<br>* inhalation powder<br>Drug: Double-dummy placebo<br>* inhalation powder<br>Drug: Salbutamol as needed<br>* inhalation powder<br>|
| Active Comparator: Fluticasone Propionate / salmeterol<br>Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA) | Drug: Fluticasone Propionate 250mcg / salmeterol 50mcg<br>* inhalation powder<br>Drug: Double-dummy placebo<br>* inhalation powder<br>Drug: Salbutamol as needed<br>* inhalation powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Trough in 24-Hour Weighted Mean FEV1 on Treatment Day 84 | Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours post-dose on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 84 values minus the Baseline value. Analysis of covariance (ANCOVA) was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1. | Baseline (Day 1) and Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Onset on Treatment Day 1 | Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1. Time to onset was calculated over 0 to 4 hours (5 min, 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose. | Baseline and Day 1 |