A Study to Evaluate the 24 Hour Spirometric Effect (FEV1) of Fluticasone Furoate/Vilanterol Inhalation Powder (100mcg Fluticasone Furoate (FF)/25mcg Vilanterol (VI)) Compared With Salmeterol/Fluticasone Propionate Inhalation Powder (50mcg Salmeterol/500mcg Fluticasone Propionate (FP))

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 Fluticasone Furoate/Vilanterol 100/25mcg once daily compared with Salmeterol/Fluticasone Propionate 50/500mcg twice daily over a 12-week treatmen 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 eligilibilty 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 of Fluticasone Furoate (FF)/Vilanterol Inhalation Powder (FF/VI Inhalation Powder) Once Daily Compared With Salmeterol/Fluticasone Propionate (FP) Inhalation Powder 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/Vilanterol 25mcg
* Drug: Fluticaosne Propionate 500mcg/Salmeterol 50mcg


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) have been hospitalised or have been treated with oral corticosteroids or antibiotics for their COPD within the last 3 years prior to Screening (Visit 1) 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/Vilanterol<br>Inhaled Corticosteroid (ICS)/Long Acting Beta Agonist (LABA) | Drug: Fluticasone Furoate 100mcg/Vilanterol 25mcg<br>* Inhalation Powder<br>|
| Active Comparator: Fluticasone Propionate/Salmeterol<br>Inhaled Corticosteroid (ICS)/Long Acting Beta Agonist (LABA | Drug: Fluticaosne Propionate 500mcg/Salmeterol 50mcg<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). The weighted mean was calculated from the pre-dose FEV1 and 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 on Treatment Day 84. Baseline trough FEV1 was 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. | Baseline 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 of onset was calculated over 0 to 4 hours (5 min, 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose. | Day 1 | 
| Change From Baseline in Trough FEV1 on Treatment Day 85 | Pulmonary function was measured by forced expiratory volume in one second (FEV1). Trough FEV1 was defined as the 24-hour FEV1 assessment, which was obtained on Day 85. Baseline is defined as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.Change from Baseline was calculated as the average of the Day 85 values minus the Baseline value. | Baseline and Day 85 |