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)

Phase 3

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

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

Registration Number: NCT01323621

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 512

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluticasone Furoate / GW642444 (vilanterol)	Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg	Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)
Fluticasone Propionate / salmeterol	Salbutamol as needed	Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)
Fluticasone Furoate / GW642444 (vilanterol)	Salbutamol as needed	Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)
Fluticasone Propionate / salmeterol	Fluticasone Propionate 250mcg / salmeterol 50mcg	Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)
Fluticasone Furoate / GW642444 (vilanterol)	Double-dummy placebo	Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)
Fluticasone Propionate / salmeterol	Double-dummy placebo	Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)

Primary Outcome Measures

Name	Time	Method
Change From Baseline Trough in 24-Hour Weighted Mean FEV1 on Treatment Day 84	Baseline (Day 1) and 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.

Secondary Outcome Measures

Name	Time	Method
Time to Onset on Treatment Day 1	Baseline and 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.